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Sample records for insulin resistance hypertension

  1. Insulin resistance in Nigerians with essential hypertension

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Keywords: Hypertension, Insulin resistance, Homeostasis model assessment ... worldwide and its prevalence is predicted to increase by 60% by 2025, when a ... model is derived from a mathematical assessment .... Drug type.

  2. Relationship between insulin resistance and plasma endothelin in hypertension patients

    International Nuclear Information System (INIS)

    Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

    2011-01-01

    To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

  3. Insulin resistance in Nigerians with essential hypertension | Akande ...

    African Journals Online (AJOL)

    Homeostasis model assessment (HOMA) was used to determine insulin resistance (IR). Results: The hypertensive subjects had significantly higher fasting insulin and HOMA-IR compared with normotensives (p =0.02 and 0.04) respectively. There were significant correlations between HOMA-IR, BMI, waist and hip ...

  4. Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis.

    Science.gov (United States)

    Wang, Feng; Han, Lili; Hu, Dayi

    2017-01-01

    Studies on the association of fasting insulin concentrations or insulin resistance with subsequent risk of hypertension have yielded conflicting results. To quantitatively assess the association of fasting insulin concentrations or homeostasis model assessment insulin resistance (HOMA-IR) with incident hypertension in a general population by performing a meta-analysis. We searched the PubMed and Embase databases until August 31, 2016 for prospective observational studies investigating the elevated fasting insulin concentrations or HOMA-IR with subsequent risk of hypertension in the general population. Pooled risk ratio (RR) and 95% confidence interval (CI) of hypertension was calculated for the highest versus the lowest category of fasting insulin or HOMA-IR. Eleven studies involving 10,230 hypertension cases were identified from 55,059 participants. Meta-analysis showed that the pooled adjusted RR of hypertension was 1.54 (95% CI 1.34-1.76) for fasting insulin concentrations and 1.43 (95% CI 1.27-1.62) for HOMA-IR comparing the highest to the lowest category. Subgroup analysis results showed that the association of fasting insulin concentrations with subsequent risk of hypertension seemed more pronounced in women (RR 2.07; 95% CI 1.19-3.60) than in men (RR 1.48; 95% CI 1.17-1.88). This meta-analysis suggests that elevated fasting insulin concentrations or insulin resistance as estimated by homeostasis model assessment is independently associated with an exacerbated risk of hypertension in the general population. Early intervention of hyperinsulinemia or insulin resistance may help clinicians to identify the high risk of hypertensive population. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

    Science.gov (United States)

    Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

    This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

  6. Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Coan, P. M.; Hummel, O.; Diaz, A. G.; Barrier, M.; Alfazema, N.; Norsworthy, P. J.; Pravenec, Michal; Petretto, E.; Hübner, N.; Aitman, T. J.

    2017-01-01

    Roč. 10, č. 3 (2017), s. 297-306 ISSN 1754-8403 R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : rat * congenic * genomic * hypertension * insulin resistance Subject RIV: EB - Gene tics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 4.691, year: 2016

  7. Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension.

    Science.gov (United States)

    Han, Tianshu; Lan, Li; Qu, Rongge; Xu, Qian; Jiang, Ruyue; Na, Lixin; Sun, Changhao

    2017-10-01

    Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown. This study assessed temporal relationship between uric acid and insulin resistance and its impact on future risk of hypertension by examining a longitudinal cohort including 8543 subjects aged 20 to 74 years from China, with an average follow-up of 5.3 years. Measurements of fasting uric acid, as well as fasting and 2-hour serum glucose and insulin, were obtained at baseline and follow-up. Indicators of hepatic and peripheral insulin resistance were calculated. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between uric acid and insulin resistance and its impact on follow-up hypertension. After adjusting for covariates, the cross-lagged path coefficients ( β 1 values) from baseline uric acid to follow-up insulin resistance indices were significantly greater than path coefficients ( β 2 values) from baseline insulin resistance indices to follow-up uric acid ( β 1 =0.110 versus β 2 =0.017; P hypertensive group were significantly greater than that in the normotensive group ( P hypertension, and the mediation effect of peripheral insulin resistance was significantly greater than that of hepatic insulin resistance (31.3% versus 13.2%; P hypertension than hepatic insulin resistance does. © 2017 American Heart Association, Inc.

  8. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

    Science.gov (United States)

    Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

    2006-12-01

    Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

  9. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  10. The Characteristic of Metabolic Changes at Insulin Resistance in Children with Primary Hypertension

    Directory of Open Access Journals (Sweden)

    N.N. Kaladze

    2013-09-01

    Full Text Available In children with hypertension we identified various metabolic disorders and the role of insulin resistance in their development, as well as compensatory mechanisms of maintaining normoglycemia.

  11. Link between insulin resistance and hypertension: What is the evidence from evolutionary biology?

    Science.gov (United States)

    Zhou, Ming-Sheng; Wang, Aimei; Yu, Hong

    2014-01-31

    Insulin resistance and hypertension are considered as prototypical "diseases of civilization" that are manifested in the modern environment as plentiful food and sedentary life. The human propensity for insulin resistance and hypertension is a product, at least in part, of our evolutionary history. Adaptation to ancient lifestyle characterized by a low sodium, low-calorie food supply and physical stress to injury response has driven our evolution to shape and preserve a thrifty genotype, which is favorite with energy-saving and sodium conservation. As our civilization evolved, a sedentary lifestyle and sodium- and energy-rich diet, the thrifty genotype is no longer advantageous, and may be maladaptive to disease phenotype, such as hypertension, obesity and insulin resistance syndrome. This article reviews human evolution and the impact of the modern environment on hypertension and insulin resistance.

  12. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    International Nuclear Information System (INIS)

    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-01-01

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET A R during insulin resistance, ET A R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET A R expression, but not ET B R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET A R pathway suppressed insulin

  13. Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents

    DEFF Research Database (Denmark)

    Andersen, U B; Dige-Petersen, H; Ibsen, H

    1999-01-01

    OBJECTIVE: To study insulin resistance in subjects with strong genetic predisposition to essential hypertension, compared with non-disposed subjects. SUBJECTS: Thirty normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 30 age- and sex matched subjects whose...... correlated to abdominal fat mass but not to insulin sensitivity. CONCLUSION: Subjects with a strong genetic predisposition to essential hypertension had increased diastolic blood pressure compared with subjects with normotensive parents, but they were not insulin resistant. This may be due to the subjects...... for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were...

  14. Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance.

    Science.gov (United States)

    Cheng, Pei-Wen; Lin, Yu-Te; Ho, Wen-Yu; Lu, Pei-Jung; Chen, Hsin-Hung; Lai, Chi-Cheng; Sun, Gwo-Ching; Yeh, Tung-Chen; Hsiao, Michael; Tseng, Ching-Jiunn; Liu, Chun-Peng

    2017-11-01

    Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1 S307 ) and suppressed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  16. Observations on the presence of insulin resistance in patients with essential hypertension and coronary heart disease

    International Nuclear Information System (INIS)

    Zhu Mei; Wu Guo

    2006-01-01

    Objective: To investigate the presence of insulin resistance in patients with essential hypertension (EH) and coronary heart disease (CHD). Methods: Fasting and 2h post oral 75g glucose blood sugar (with oxidase method), insulin and C-peptide (with RIA) levels were examined in 52 patients with EH, 40 patients with CHD and 35 controls. Results: The fasting and 2h post o- ral glucose serum levels of glucose, insulin and C-peptide in the patients were significantly higher than those in the controls (P < 0.01), suggesting presence of impaired glucose tolerance and insulin resistance. Conclusion: Impaired glucose tolerance due to insulin resistance was demonstrated in the studied patients with EH or CHD. (authors)

  17. Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

    Science.gov (United States)

    Peyton, Kelly J; Liu, Xiao-Ming; Shebib, Ahmad R; Johnson, Fruzsina K; Johnson, Robert A; Durante, William

    2018-04-27

    This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age. The increase in arginase activity in obese animals was associated with a decrease in insulin sensitivity and circulating levels of arginine and NO. The rise in arginase activity also preceded the increase in blood pressure in obese ZR detected at 12 weeks of age. Chronic treatment of 8-week-old obese animals with an arginase inhibitor or L-arginine for 4 weeks prevented the development of hypertension and improved plasma concentrations of arginine and NO. Arginase inhibition also improved insulin sensitivity in obese ZR while L-arginine supplementation had no effect. In conclusion, arginase inhibition prevents the development of hypertension and improves insulin sensitivity while L-arginine administration only mitigates hypertension in obese animals. Arginase represents a promising therapeutic target in ameliorating obesity-associated vascular and metabolic dysfunction.

  18. Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients.

    Science.gov (United States)

    Della Mea, Paolo; Lupia, Mario; Bandolin, Valentina; Guzzon, Samuele; Sonino, Nicoletta; Vettor, Roberto; Fallo, Francesco

    2005-01-01

    Adiponectin is an adipocyte-derived protein with insulin-sensitizing and antiatherogenic properties. Failure to decrease blood pressure (BP) normally during night in hypertensive patients has been independently associated with left ventricular hypertrophy. We examined the relationship between adiponectin levels, insulin sensitivity, and left ventricular structure in 40 newly diagnosed never-treated patients with essential hypertension, including 20 patients with a normal night-time pressure decrease (ie, dippers) and 20 patients with BP persistently elevated throughout the 24-h period (ie, nondippers). All subjects had grade 1-2 hypertension, aged 18 to 65 years, no diabetes mellitus, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease. The two groups of patients were similar for age, sex, body mass index, and had no differences for clinic, 24-h, and diurnal BP, and 24-h, diurnal, and nocturnal heart rate, as well as glucose, total cholesterol, and triglyceride levels. Plasma insulin and homeostasis model assessment (HOMA index) were higher (P < .01), and adiponectin levels were lower (P < .005) in nondippers than in dippers. Adiponectin correlated inversely with HOMA index and insulin levels (r = -0.58, and r = -0.62, respectively, P < .001) in the entire population. Nondippers showed left ventricular mass, relative wall thickness, and measure of early and late diastolic peak flow velocity ratio similar to those of dippers. In the absence of major cardiovascular risk factors, nondipper essential hypertensive patients show more prominent insulin resistance and lower adiponectin compared to dippers. Therapeutic modulation of adiponectin or insulin resistance might provide additional benefit to the conventional antihypertensive treatment.

  19. A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

    DEFF Research Database (Denmark)

    Olsen, M H; Andersen, U B; Wachtell, K

    2000-01-01

    We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension....

  20. Gamma-glutamyltransferase, fatty liver index and hepatic insulin resistance are associated with incident hypertension in two longitudinal studies.

    Science.gov (United States)

    Bonnet, Fabrice; Gastaldelli, Amalia; Pihan-Le Bars, Florence; Natali, Andrea; Roussel, Ronan; Petrie, John; Tichet, Jean; Marre, Michel; Fromenty, Bernard; Balkau, Beverley

    2017-03-01

    We hypothesized that liver markers and the fatty liver index (FLI) are predictive of incident hypertension and that hepatic insulin resistance plays a role. The association between liver markers and incident hypertension was analysed in two longitudinal studies of normotensive individuals, 2565 from the 9-year data from an epidemiological study on the insulin resistance cohort and the 321 from the 3-year 'Relationship between Insulin Sensitivity and Cardiovascular disease' cohort who had a measure of endogenous glucose production. The FLI is calculated from BMI, waist circumference, triglycerides and gamma-glutamyltransferase (GGT) and the hepatic insulin resistance index from endogenous glucose production and fasting insulin. The incidence of hypertension increased across the quartiles groups of both baseline GGT and alanine aminotransferase. After adjustment for sex, age, waist circumference, fasting glucose, smoking and alcohol intake, only GGT was significantly related with incident hypertension [standardized odds ratio: 1.21; 95% confidence interval (1.10-1.34); P = 0.0001]. The change in GGT levels over the follow-up was also related with an increased risk of hypertension, independently of changes in body weight. FLI analysed as a continuous value, or FLI at least 60 at baseline were predictive of incident hypertension in the multivariable model. In the RISC cohort, the hepatic insulin resistance index was positively related with the risk of 3-year incident hypertension [standardized odds ratio: 1.54 (1.07-2.22); P = 0.02]. Baseline GGT and FLI, as well as an increase in GGT over time, were associated with the risk of incident hypertension. Enhanced hepatic insulin resistance predicted the onset of hypertension and may be a link between liver markers and hypertension.

  1. Relationships between endothelin and insulin receptor of red blood cell and insulin resistance in patients with hypertension

    International Nuclear Information System (INIS)

    Tong Qian; Zheng Yang; Xu Hui

    2004-01-01

    Objective: To find the relationships between endothelin (ET) and insulin resistance (IR) and insulin receptor (INSR) in patients with essential hypertension. Methods: Forty patients including 20 cases of essential hypertension disease (EHD) and 20 health persons were divided into experimental group and control group. Blood glucose, serum insulin, ET and the number of erythrocyte INSR in all patients during fasting condition were detected by radioimmunoassay and radiometric analysis. Results: Both insulin sensitivity index (ISI) and the number of INSR in EHD group were much less than that of control group, on the contrary, ET level of EHD group was significantly higher than that of control group (P<0.05). Statistical analysis demonstrated a negative correlation between ET and ISI and INSR number existed in EHD group. Conclusion: IR is a common phenomenon in patient with EHD and possibly due to decrease of INSR number. The ET levels are higher in patients with EHD than that in health people and correlate with INSR, and the change of INSR number is the possible mediator for their relationship

  2. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

    Science.gov (United States)

    Grassi, Davide; Necozione, Stefano; Lippi, Cristina; Croce, Giuseppe; Valeri, Letizia; Pasqualetti, Paolo; Desideri, Giovambattista; Blumberg, Jeffrey B; Ferri, Claudio

    2005-08-01

    Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, Pbenefit if included as part of a healthy diet for patients with EH.

  3. [Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis].

    Science.gov (United States)

    Pedersen, O

    1992-05-11

    Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  5. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

  6. Insulin resistance, its association with diastolic left ventricular disease and aorta elasticity in hypertensive patients

    Directory of Open Access Journals (Sweden)

    E.I. Shorikov

    2017-04-01

    Full Text Available Background. The accepted threshold of insulin resistance value in arterial hypertension (AH is absent, thus it is relevant to determine its degree in patients with AH, and to determine the interaction between the insulin resistance (IR syndrome and the target organs injury. The purpose of our study was to set the threshold of IR in patients with AH, to define association between the IR parameters, presence of diastolic dysfunction and the state of aorta elasticity. Materials and methods. Investigation included 229 patients with AH and type 2 diabetes mellitus (DM, as well as 108 patients with the isolated AH. There were used clinical, instrumental, biochemical (HOMA-2 model, HOMA-IR indices, statistical methods. Results. The course of the isolated AH and AH with concomitant type 2 DM is associated with IR development, that it is well-proven in the model of HOMA-2 (р < 0.001. In patients with comorbid patho­logy the sensitiveness of peripheral tissues to insulin depends on severity of AH (р < 0.001. Presence of IR in HOMA-IR model was revealed in patients with the isolated AH in 26.6 % of cases. The level of plasma insulin grows substantially, and the tissues sensitiveness to insulin declined at the third type of diastolic dysfunction (р < 0.05. The coefficients of aorta elasticity have a reverse correlation with all parameters of НОМА-2 model determined by the levels of glucose (р < 0.001, insulin (p < 0.05, coefficient НОМА-IR (p < 0.05 and direct association with the degree of peri­pheral tissues sensitivity to insulin (p < 0.01. Conclusions. The threshold of IR by HOMA-2 model in patients was set at the level of 1.87; the increase of aorta inflexibility and diastolic dysfunction severity depend on IR severity.

  7. Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension.

    Science.gov (United States)

    Zizek, B; Poredos, P

    2001-02-01

    To evaluate whether endothelium-dependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between flow-mediated vasodilation (FMD) and hyperinsulinaemia/insulin resistance. Cross-sectional study. Angiology department at a teaching hospital. The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age-matched, normotensive volunteers as controls. We also investigated 41 normotonics with FT aged 20-30 (25) years and 41 age-and sex-matched controls without FT. Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. In hypertonics FMD was significantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P=0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was comparable in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). In treated patients with EH, flow-mediated dilation of the BA as well as endothelium-independent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications.

  8. Resistant hypertension.

    Science.gov (United States)

    Wei, Fang-Fei; Zhang, Zhen-Yu; Huang, Qi-Fang; Yang, Wen-Yi; Staessen, Jan A

    2018-06-15

    The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment-resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure lowering medications. As we demonstrate in this review, this idea so attractive to manufacturers and invasive cardiologists and radiologists overlooked decades of careful pathophysiological research in a disease, which still remains enigmatic but remains the major cause of cardiovascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of the ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices and in the future research. Throughout our review, we focused on new evidence became available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

  9. [Significance of insulin resistance in the pathogenesis of sarcopenia and chronic heart failure in elderly hypertensive patients].

    Science.gov (United States)

    Gorshunova, N K; Medvedev, N V

    2016-01-01

    To determine the pathogenic role of insulin resistance in the formation of involutive sarcopenia and chronic heart failure (CHF) were examined 88 elderly patients with arterial hypertension (AH) and 32 elderly patients without cardiovascular disease by methods of carbohydrate metabolism and the level of brain natriuretic peptide precursor evaluation, muscle mass and strength measuring, echocardiography, 6 minute walking test. It was found that in the group of hypertensive patients with low mass and muscle strength significantly increased indices of insulin resistance and more expressed signs of the left ventricle myocardial dysfunction and functional class of heart failure, probably as a result of disorders of energy homeostasis, resulting from the deterioration of glucose into the muscle cells of the heart and skeletal muscles.

  10. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients...

  11. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  12. Short-term endurance training after coronary artery bypass grafting improves insulin resistance parameters in patients with hypertension.

    Science.gov (United States)

    Borowicz-Bieńkowska, Sławomira; Przywarska, Izabela; Dylewicz, Piotr; Pilaczyńska-Szcześniak, Łucja; Rychlewski, Tadeusz; Wilk, Małgorzata; Rózańska, Anna

    2004-05-01

    It has been shown that short-term exercise training improves insulin resistance parameters in patients with ischaemic heart disease. The effects of such a rehabilitation programme in patients with hypertension have not been well established. To assess whether short-term endurance training after coronary artery bypass grafting (CABG) may improve metabolic parameters and reduce blood pressure in patients with hypertension. The study group consisted of 30 male patients (15 with hypertension and 15 normotensive) aged 55+/-2.1 years who underwent CABG 1 to 6 months before the initiation of a 3-week endurance training. Glucose, insulin and C-peptide blood levels as well as binding and degradation of 125I-insulin by erythrocyte receptors were assessed before and after the training programme. The effects of training on blood pressure values were also evaluated. A significant improvement (phypertension. This was accompanied by a significant (phypertension, both the exercise systolic and diastolic pressures decreased significantly (pendurance training was especially effective in patients with hypertension in whom beneficial changes in some metabolic risk factors of ischaemic heart disease as well as the reduction in the blood pressure values were observed.

  13. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

    Science.gov (United States)

    Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

    2013-06-15

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature.

  14. Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents

    DEFF Research Database (Denmark)

    Andersen, U B; Dige-Petersen, H; Ibsen, H

    1999-01-01

    -ray absorptiometry; (4) an exercise test with gas exchange analysis; and (5) investigation of composition of usual diet by diet registration for 5 days. RESULTS: The 24-h diastolic blood pressure was higher in subjects predisposed to hypertension compared with the controls: 78.1 versus 74.0 mmHg (confidence interval...... for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were...

  15. Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus.

    Science.gov (United States)

    Rahman, Md Mahbubur; Kwon, Han-Sol; Kim, Myung-Jin; Go, Hyeon-Kyu; Oak, Min-Ho; Kim, Do-Hyung

    2017-08-01

    The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5mg/kg twice daily and 40min swimming/day 5days/week were regimented after diabetes induction. Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (Phypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (Phypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Diastolic dysfunction is associated with insulin resistance, but not with aldosterone level in normotensive offspring of hypertensive families.

    Science.gov (United States)

    Zizek, Bogomir; Poredos, Pavel; Trojar, Andrej; Zeljko, Tadej

    2008-01-01

    We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28-39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (E(m) and E(m)/A(m) ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. In subjects with FT, the LV mass was higher than in controls (92.14 +/- 24.02 vs. 70.08 +/- 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower E(m) and E(m)/A(m) ratio; p < 0.001). In subjects with FT, the E(m)/A(m) ratio was independently associated with IR (partial p = 0.029 in multivariate model, R(2) = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease. (c) 2008 S. Karger AG, Basel.

  17. CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2015-09-01

    Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

  18. Insulin resistance: definition and consequences.

    Science.gov (United States)

    Lebovitz, H E

    2001-01-01

    Insulin resistance is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population. Insulin action is the consequence of insulin binding to its plasma membrane receptor and is transmitted through the cell by a series of protein-protein interactions. Two major cascades of protein-protein interactions mediate intracellular insulin action: one pathway is involved in regulating intermediary metabolism and the other plays a role in controlling growth processes and mitoses. The regulation of these two distinct pathways can be dissociated. Indeed, some data suggest that the pathway regulating intermediary metabolism is diminished in type 2 diabetes while that regulating growth processes and mitoses is normal.--Several mechanisms have been proposed as possible causes underlying the development of insulin resistance and the insulin resistance syndrome. These include: (1) genetic abnormalities of one or more proteins of the insulin action cascade (2) fetal malnutrition (3) increases in visceral adiposity. Insulin resistance occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Insulin Resistance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome depending on the genetic background of the individual developing the insulin resistance.--In this context, we need to consider whether insulin resistance should be defined as a disease entity which needs to be diagnosed and treated with specific drugs to improve insulin action.

  19. Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring

    Directory of Open Access Journals (Sweden)

    Anne-Maj eSamuelsson

    2013-02-01

    Full Text Available Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, in particular obesity, insulin resistance and hypertension. We tested the hypothesis that a maternal diet rich in simple sugars predispose mouse offspring to obesity, glucose intolerance and cardiovascular diseases in adulthood.Female C57BL/6J mice were fed either a standard chow or a sucrose-rich diet (26% of total energy 6 weeks prior to mating, throughout pregnancy and lactation. Offspring of control dams (OC and high sucrose fed dams (OSF were weaned onto standard control chow, and metabolic and cardiovascular parameters determined at 3 months of age. Both male and female OSF were hyperphagic by 4 weeks of age and females were heavier than OC at 9 weeks. At 3 months, female OSF showed a significant increase in inguinal fat pad mass, whereas skeletal muscle mass (tibialis anterior and locomotor activity were decreased relative to OC. A ten-fold increase in fasting serum insulin in female OSF versus OC at 3 months (Insulin [pmol/L] mean±SEM, OSF, 200.3±16.1, versus OC, 20.3±1.8, n=6 P<0.001, was associated with impaired glucose tolerance (AUC [mmol/L min] mean±SEM, OSF 1437.4±124.2 versus OC, 1076.8±83.9, n=6, P<0.05. Both male and female OSF were hypertensive as assessed by radiotelemetry (night-time systolic arterial pressure [mmHg] mean±SEM, male OSF, 128±1 versus OC, 109±1, n=6, P<0.01; female OSF, 130±1 versus OC, 118±1, n=6, P<0.05. Analysis of heart rate variability demonstrated an increased low:high frequency ratio in male and female OSF (P<0.05, indicative of heightened sympathetic efferent tone. Renal tissue noradrenaline content was markely raised in the OSF versus OC (noradrenaline [pg/ml/mg tissue] mean±SEM, male OSF, 2.28±0.19 versus OC 0.84±0.09, n=6, P<0.01 . Exposure to a maternal diet rich in sucrose led to obesity and glucose intolerance in female mice offspring, and hypertension in both sexes.

  20. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Your Baby is Born Monogenic Diabetes Insulin Resistance & Prediabetes Insulin resistance and prediabetes occur when your body ... will stay in the healthy range. What is prediabetes? Prediabetes means your blood glucose levels are higher ...

  1. [Hypertension and insulin treatment in type 2 diabetes].

    Science.gov (United States)

    Ben Salem Hachmi, L; Bouguerra, R; Maatki, O; Smadhi, H; Turki, Z; Hraoui, S; Ben Slama, C

    2007-08-01

    Insulin resistance and endogenous hyperinsulinemia are associated with blood hypertension. The aim of this analysis is to estimate the prevalence of blood hypertension one year after insulin treatment in type 2 diabetic patients. and methods: This is a retrospective clinical study of 178 type 2 diabetic patients (57 men and 121 women) insulin treated since at least one year. Mean age is 62 +/- 10 years and mean duration of diabetes is ten years. All patients had a clinical and biological control before treatment with insulin and at least three controls during the first year of insulin treatment (anthropometric measurements, blood pressure, fasting plasma glucose, HbA1C). WHO definition of hypertension is used (blood pressure >or=140 / 90 mmHg). At baseline, 48% of patients have hypertension. After insulin treatment, the prevalence of hypertension significantly increase to 53% (94 / 178) three months later (p=0.008), to 54.5% (98 / 178) six months later (p=0.001) and to 55.6% (99 / 178) twelve months later. This increase in hypertension frequency is associated with a significant weight gain and a better blood glucose control. Insulin therapy may contribute to the development of blood hypertension. It promotes renal sodium retention and increases sympathetic nervous system activity. In the UKPDS intensive blood glucose control with insulin is not associated with an increase of macro vascular complications. These observational data suggest the need for further study of the relationship between exogenous insulin and hypertension.

  2. Dietary intake and cardiometabolic biomarkers in relation to insulin resistance and hypertension in a middle-aged and elderly population in Beijing, China.

    Science.gov (United States)

    Wang, Jia; Hong, Zhongxin; Wu, Li; Ding, Bingjie; Bi, Yanxia; Gu, Zhongyi; Li, Wei

    2017-08-01

    This study investigated the relationships of dietary intake and cardiometabolic biomarkers with insulin resistance and hypertension in rural middle-aged and elderly people in China. One hundred and eight middle-aged and elderly adults were recruited in Zhangfang village in May 2014. We measured blood pressure, anthropometric parameters, and biochemical indexes, including high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, and blood lipids. Homeostasis model assessment of insulin resistance index (HOMA-IR) was assessed on the basis of fasting glucose and insulin. We recorded participant demographic characteristics, dietary intake, and lifestyle using questionnaires. Hypertensive participants had higher levels of triglycerides (TG), hsCRP, sICAM-1, body fat percentage (BF%), arm muscle circumference (AMC) and HOMA-IR than nonhypertensive individuals. Hypertensive participants had higher carbohydrate intake but lower intakes of protein and fat. Carbohydrate intake was positively correlated with hsCRP, sICAM-1, TG, BF%, and HOMA-IR, and was negatively correlated with AMC. Protein and fat intakes were negatively correlated with hsCRP and sICAM-1. Protein intake was also significantly negatively correlated with TG and HOMA-IR, and positively correlated with AMC. HOMA-IR was positively correlated with hsCRP, sICAM-1, TG and BF%, and negatively correlated with AMC. Multivariable linear regression indicated that TG, sICAM-1, and hsCRP were significantly associated with HOMA-IR. In conclusion, in a rural Chinese population, high intake of carbohydrate and low intake of fat and protein were associated with insulin resistance and hypertension, possibly by increasing inflammatory factors such as sICAM-1 and hsCRP, increasing BF% and increasing the level of plasma TG.

  3. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    Langeveld, Mirjam; Aerts, Johannes M. F. G.

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

  4. Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

    2000-01-01

    Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

  5. Essential Hypertension in Adolescents: Association with Insulin Resistance and with Metabolism of Homocysteine and Vitamins

    Czech Academy of Sciences Publication Activity Database

    Kahleová, R.; Palyzová, D.; Zvára, Karel; Zvárová, Jana; Hrach, Karel; Nováková, I.; Hyánek, J.; Bendlová, B.; Kožich, V.

    2002-01-01

    Roč. 15, - (2002), s. 857-864 ISSN 0895-7061 R&D Projects: GA MŠk LN00B107 Keywords : hypertension * homocysteine * gene * adolescent Subject RIV: BD - Theory of Information Impact factor: 2.613, year: 2002

  6. Relationship between insulin resistance and blood lipid and sport in patients with type II diabetes mellitus complicated with hypertension%2型糖尿病合并高血压患者胰岛素低抗

    Institute of Scientific and Technical Information of China (English)

    谭丽艳; 杨红玉; 柴国禄; 沈凌元

    2001-01-01

    Objective To study the relationship between insulin resistance and blood pressure and blood lipid in patients with type II diabetes mellitus complicated with hypertension.Methods The serum concentration of fasting glucose,insulin,lipids and the level of blood pressure were measured in 56 patients with type II diabetes mellitus complicated with hypertension.Results The insulin sensitivity index(ISI) decreased in patients with type II diabetes mellitus complicated with hypertension compared with the patients with type II diabetes mellitus with normal blood pressure(P< 0.05).A negative correlation with hypertension was found between ISI and SBP,DBP,TG,ApoB in patients with type II diabetes mellitus complicated with hypertension(P<0.05).There was a positive correlation between ISI and HDL in patients with type II diabetes mellitus complicated with hypertension(P<0.05).Conclusion Insulin resistance presents in patients of type II diabetes mellitus complicated with hypertension.Insulin resistance is the major cause of hypertension and lipid metabolic disturbance in patients with type II diabetes mellitus complicated with hypertension.

  7. Hypertension in Obese Type 2 Diabetes Patients is Associated with Increases in Insulin Resistance and IL-6 Cytokine Levels: Potential Targets for an Efficient Preventive Intervention

    Directory of Open Access Journals (Sweden)

    Ljiljana Lukic

    2014-03-01

    Full Text Available Increased body weight as well as type 2 diabetes (T2D are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this study we compared the levels of insulin resistance (IR:OGIS, plasma insulin (PI:RIA levels, and pro-inflammatory cytokines (IL-6 and TNF-α: ELISA, being risk factors previously found to be associated with hypertension, in T2D patients showing increased body weight (obese and overweight, BMI ≥ 25 kg/m2 with hypertension (group A, N = 30, or without hypertension (group B, N = 30, and in nonobese (BMI < 25 kg/m2, normotensive controls (group C, N = 15. We found that OGIS index was the lowest (A: 267 ± 35.42 vs. B: 342.89 ± 32.0, p < 0.01 and PI levels were the highest (A: 31.05 ± 8.24 vs. B: 17.23 ± 3.23, p < 0.01 in group A. In addition, IL-6 levels were higher in group A (A: 15.46 ± 5.15 vs. B: 11.77 ± 6.09; p < 0.05 while there was no difference in TNF-α levels. Our results have shown that appearance of hypertension in T2D patients with increased body weight was dependent on further increase in IR which was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply that lifestyle intervention aimed to decrease IR might be beneficial in reducing the risk for hypertension in those T2D individuals.

  8. Insulin Resistance of Puberty.

    Science.gov (United States)

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

  9. Selective Insulin Resistance in the Kidney

    Science.gov (United States)

    Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

    2016-01-01

    Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

  10. Insulin resistance in dairy cows.

    Science.gov (United States)

    De Koster, Jenne D; Opsomer, Geert

    2013-07-01

    Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Adipokines and Hepatic Insulin Resistance

    Science.gov (United States)

    Hassan, Waseem

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

  12. [Resistant hypertension: An update].

    Science.gov (United States)

    Renna, N F

    2018-02-04

    An estimated 10% to 20% of hypertensive patients could be considered resistant to treatment (RH). These are patients who are not controlled using three drugs, at the maximum tolerated doses, including a diuretic, as well as those with high blood pressure controlled using four or more drugs. The term is used to identify patients that might benefit from special diagnostic and/or therapeutic consideration. The term 'refractory hypertension' has recently been proposed as a novel phenotype of antihypertensive failure. It refers to patients whose blood pressure cannot be controlled with maximum treatment. The first studies of this phenotype indicate that it is rare and affects less than 5% of patients with RH. Adherence to or compliance with medical treatment is key to defining resistant hypertension. Closer attention has been paid to clinical and experimental research since the first scientific statement for the diagnosis, assessment and treatment of RH from the American Heart Association, and in the European guidelines, was published in 2008. This review will set out the concepts relating to prevalence, prognosis and compliance and cover the latest developments on this subject. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Prevalence of the insulin resistance syndrome in obesity

    OpenAIRE

    Viner, R; Segal, T; Lichtarowicz-Kryn..., E; Hindmarsh, P

    2005-01-01

    Aims: To assess prevalence of the insulin resistance syndrome (IRS: obesity, abnormal glucose homoeostasis, dyslipidaemia, and hypertension) in obese UK children and adolescents of different ethnicities and to assess whether fasting data is sufficient to identify IRS in childhood obesity.

  14. The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance.

    Science.gov (United States)

    Lan, Jianjun; Chen, Xiaoni; Chen, Xiaoping; Wang, Si; Zhang, Xin; Wu, Kai; He, Sen; Peng, Yong; Jiang, Lingyun; Li, Longxin; Wan, Liyan

    2011-10-01

    To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients. A total of 81 non-diabetic EH patients, including 54 with IR and 27 without IR, were enrolled. After two weeks wash-out, patients with IR were randomly assigned to telmisartan (group T) or amlodipine (group A) for 6 months. Blood samples were taken before and after treatment for measurement of routine biochemical parameters, visfatin and insulin resistance (measured by HOMA-IR). Visfatin was independently correlated with HOMA-IR (r=0.845, P=0.000). After 6 months of treatment, both drugs lowered HOMA-IR, more significantly so in group T than group A (P=0.010). Serum visfatin levels increased in group T but decreased in group A. Serum visfatin levels were higher in non-diabetic EH patients with IR compared with those without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin increased with telmisartan yet decreased with amlodipine treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  16. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  17. Folate Deficiency Is Associated With Oxidative Stress, Increased Blood Pressure, and Insulin Resistance in Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kožich, V.; Krijt, J.; Sokolová, J.; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Šilhavý, Jan; Oliyarnyk, O.; Kazdová, L.; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 1 (2013), s. 135-140 ISSN 0895-7061 R&D Projects: GA MZd(CZ) NS10036; GA MŠk(CZ) ME10019; GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : blood pressure * ectopic fat accumulation * folate deficiency * homocysteine * hypertension * oxidative stress * spontaneously hypertensive rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  18. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  19. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C.; Coster, Adelle C. F.; Stöckli, Jacqueline; James, David E.

    2015-01-01

    Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. PMID:25720492

  20. Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

    Science.gov (United States)

    Chuang, L M; Hsiung, C A; Chen, Y D; Ho, L T; Sheu, W H; Pei, D; Nakatsuka, C H; Cox, D; Pratt, R E; Lei, H H; Tai, T Y

    2001-11-01

    The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our

  1. The evolutionary benefit of insulin resistance

    NARCIS (Netherlands)

    Soeters, Maarten R.; Soeters, Peter B.

    2012-01-01

    Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in

  2. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

    OpenAIRE

    Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

    2013-01-01

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...

  3. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  4. Resistant Hypertension and Cardiorenovascular Risk

    Directory of Open Access Journals (Sweden)

    Prkacin Ingrid

    2017-06-01

    Full Text Available Studies have documented independent contribution of sympathetic activation to the cardiovascular disease continuum. Hypertension is one of the leading modifiable factors. Most if not all the benefit of antihypertensive treatment depends on blood pressure lowering, regardless how it is obtained. Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of the concurrent use of three antihypertensive drugs of different classes. Ideally, one of the three drugs should be a diuretic, and all drugs should be prescribed at optimal dose amounts. Poor adherence to antihypertensive therapy, undiscovered secondary causes (e.g. obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and lifestyle factors (e.g. obesity, excessive sodium intake, heavy alcohol intake, various drug interactions are the most common causes of resistant hypertension. Cardio(renovascular morbidity and mortality are significantly higher in resistant hypertensive than in general hypertensive population, as such patients are typically presented with a long-standing history of poorly controlled hypertension. Early diagnosis and treatment is needed to avoid further end-organ damage to prevent cardiorenovascular remodeling. Treatment strategy includes lifestyle changes, adding a mineralocorticoid receptor antagonist, treatment adherence in cardiovascular prevention and, in case of failure to control blood pressure, renal sympathetic denervation or baroreceptor activation therapy. The comparative outcomes in resistant hypertension deserve better understanding. In this review, the most current approaches to resistant hypertension and cardiovascular risk based on the available literature evidence will be discussed.

  5. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

  6. Paediatrics, insulin resistance and the kidney.

    Science.gov (United States)

    Marlais, Matko; Coward, Richard J

    2015-08-01

    Systemic insulin resistance is becoming more prevalent in the young due to modern lifestyles predisposing to the metabolic syndrome and obesity. There is also evidence that there are critical insulin-resistant phases for the developing child, including puberty, and that renal disease per se causes systemic insulin resistance. This review considers the factors that render children insulin resistant, as well as the accumulating evidence that the kidney is an insulin-responsive organ and could be affected by insulin resistance.

  7. TLR4 and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Jane J. Kim

    2010-01-01

    Full Text Available Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4, involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide and endogenous ligands (e.g., free fatty acids which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.

  8. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls.

    Science.gov (United States)

    Legro, Richard S; Castracane, V Daniel; Kauffman, Robert P

    2004-02-01

    Approximately 50% to 70% of all women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and this hormone insensitivity probably contributes to the hyperandrogenism that is responsible for the signs and symptoms of PCOS. Although uncertainty exists, early detection and treatment of insulin resistance in this population could ultimately reduce the incidence or severity of diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease. Even if that proves to be the case, there are still several problems with our current approach to insulin sensitivity assessment in PCOS, including the apparent lack of consensus on what defines PCOS and "normal" insulin sensitivity, ethnic and genetic variability, the presence of other factors contributing to insulin resistance such as obesity, stress, and aging, and concern about whether simplified models of insulin sensitivity have the precision to predict treatment needs, responses, and future morbidity. Although the hyperinsulinemic-euglycemic clamp technique is the gold standard for measuring insulin sensitivity, it is too expensive, time-consuming, and labor-intensive to be of practical use in an office setting. Homeostatic measurements (fasting glucose/insulin ratio or homeostatic model assessment [HOMA] value) and minimal model tests (particularly the oral glucose tolerance test [OGTT]) represent the easiest office-based assessments of insulin resistance in the PCOS patient. The OGTT is probably the best simple, office-based method to assess women with PCOS because it provides information about both insulin resistance and glucose intolerance. The diagnosis of glucose intolerance holds greater prognostic and treatment implications. All obese women with PCOS should be screened for the presence of insulin resistance by looking for other stigmata of the insulin resistance syndrome such as hypertension, dyslipidemia, central obesity, and glucose intolerance.

  9. Insulin resistance in therapeutic clinic

    Directory of Open Access Journals (Sweden)

    Anna V. Pashentseva

    2017-09-01

    Full Text Available Today an obesity became the global epidemic striking both children, and adults and represents one of the most important problems of health care worldwide. Excess accumulation of fatty tissue is resulted by insulin resistance and a compensatory hyperinsulinaemia which are the main predictors of development of a diabetes mellitus type 2. Insulin resistance is also one of key links of a pathogenesis of such diseases as cardiovascular pathology, not-alcoholic fatty liver disease, a polycystic ovary syndrome, gestational diabetes and many others. Depression of sensitivity of tissues to insulin can be physiological reaction of an organism to stress factors and pathological process. The endogenic reasons also take part in development of insulin resistance besides factors of the external environment. The role of genetic predisposition, a subclinical inflammation of fatty tissue, thyroid hormones, adipokines and vitamin D in formation of this pathological process is studied. As insulin resistance takes part in a pathogenesis of various diseases, methods of its diagnostics and correction are of great importance in therapeutic practice. At purpose of treatment it is worth giving preference to the drugs which are positively influencing sensitivity of tissues to insulin.

  10. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  11. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  12. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  13. Obesity genes and insulin resistance.

    Science.gov (United States)

    Belkina, Anna C; Denis, Gerald V

    2010-10-01

    The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of 'metabolically healthy but obese' (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients.

  14. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    incidence of insulin resistance and type 2 diabetes is ..... 10% SDS-PAGE and then subjected to Western blot analysis with anti-pPDK1, pAkt/Akt or anti-pPKCε antibodies (1:1000). ... in humans, where qualitative and quantitative abnormalities.

  15. Insulin resistance in obesity can be reliably identified from fasting plasma insulin

    NARCIS (Netherlands)

    ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

    2015-01-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

  16. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  17. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  18. Insulin resistance and bone: a biological partnership.

    Science.gov (United States)

    Conte, Caterina; Epstein, Solomon; Napoli, Nicola

    2018-04-01

    Despite a clear association between type 2 diabetes (T2D) and fracture risk, the pathogenesis of bone fragility in T2D has not been clearly elucidated. Insulin resistance is the primary defect in T2D. Insulin signalling regulates both bone formation and bone resorption, but whether insulin resistance can affect bone has not been established. On the other hand, evidence exists that bone might play a role in the regulation of glucose metabolism. This article reviews the available experimental and clinical evidence on the interplay between bone and insulin resistance. Interestingly, a bilateral relationship between bone and insulin resistance seems to exist that unites them in a biological partnership.

  19. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  20. Streptozotocin diabetes and insulin resistance impairment of ...

    African Journals Online (AJOL)

    ... insulin resistance impairment of spermatogenesis in adult rat testis: Central Vs local ... Summary: Mammalian reproduction is dynamically regulated by the pituitary ... Group 3 > Streptozotocin-insulin treated group; received a single dose IP ...

  1. Decoding resistant hypertension signalling pathways.

    Science.gov (United States)

    Parreira, Ricardo Cambraia; Lacerda, Leandro Heleno Guimarães; Vasconcellos, Rebecca; Lima, Swiany Silveira; Santos, Anderson Kenedy; Fontana, Vanessa; Sandrim, Valéria Cristina; Resende, Rodrigo Ribeiro

    2017-12-01

    Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  2. Triiodothyronine : a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, SJL; ter Maaten, JC; Popp-Snijders, C; Heine, RJ; Gans, ROB

    1999-01-01

    Objective Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis

  3. Triiodothyronine: a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, J.L.; ter Maaten, J.C; Popp-Snijders, C.; Heine, R.J.; Gans, R.O.B.

    1999-01-01

    Objective. Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis

  4. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  5. Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

    Science.gov (United States)

    Govindsamy, Annelene; Naidoo, Strinivasen

    2018-01-01

    Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology. PMID:29484207

  6. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  7. Relationship between blood pressure and insulin resistance in patients with gestational diabetes

    International Nuclear Information System (INIS)

    Kan Shujuan; Zhang Sujuan

    2008-01-01

    Objective: To study the relationship existe between blood pressure level and degree of insulin resistance in patients with gestational diabetes. Methods: Ninety-five cases of gestational diabetes were diagnosed among 350 pregnant women. Of them, 55 were found to be hypertensive and 40 were normotensive. Fasting, 1,2, 3h post-prandial (75g glucose) blood sugar (with peroxidase method) levels and fasting insulin (with RIA) levels were measured in these patients and 85 normal pregnant women (as control). Results: Fasting, 1, 2, 3h post 75g glucose blood sugar and fasting insulin levels in the 55 hypertensive diabetics were significantly higher than those in the normotensives and controls (P<0.05). The calculated insulin sensitivity indices were significantly lower (P also < 0.05). Conclusion: A higher insulin resistance existed in hypertensive gestational diabetics which might be a risk factor of developing hypertension. (authors)

  8. Associations between depressive symptoms and insulin resistance

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Nijpels, G

    2006-01-01

    AIMS/HYPOTHESIS: The association between depression and insulin resistance has been investigated in only a few studies, with contradictory results reported. The aim of this study was to determine whether the association between symptoms of depression and insulin resistance varies across glucose...... established type 2 diabetes mellitus. Main outcome measures were insulin resistance defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and symptoms of depression using the Centre for Epidemiologic Studies Depression Scale (CES-D). RESULTS: In the total sample, we found a weak.......942). The association between depressive symptoms and insulin resistance was similar for men and women. CONCLUSIONS/INTERPRETATION: We found only weak associations between depressive symptoms and insulin resistance, which did not differ among different glucose metabolism subgroups or between men and women....

  9. Childhood obesity and insulin resistance: how should it be managed?

    Science.gov (United States)

    Ho, Mandy; Garnett, Sarah P; Baur, Louise A

    2014-12-01

    Concomitant with the rise in global pediatric obesity in the past decades, there has been a significant increase in the number of children and adolescents with clinical signs of insulin resistance. Given insulin resistance is the important link between obesity and the associated metabolic abnormalities and cardiovascular risk, clinicians should be aware of high risk groups and treatment options. As there is no universally accepted biochemical definition of insulin resistance in children and adolescents, identification and diagnosis of insulin resistance usually relies on clinical features such as acanthosis nigricans, polycystic ovary syndrome, hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Treatment for reducing insulin resistance and other obesity-associated comorbidities should focus on changes in health behaviors to achieve effective weight management. Lifestyle interventions incorporating dietary change, increased physical activity, and decreased sedentary behaviors, with the involvement of family and adoption of a developmentally appropriate approach, should be used as the first line treatment. Current evidence suggests that the primary objective of dietary interventions should be to reduce total energy intake and a combination of aerobic and resistance training should be encouraged. Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity. Ongoing evaluation and research are required to explore optimal protocol and long-term effectiveness of lifestyle interventions, as well as to determine whether the improvements in insulin sensitivity induced by lifestyle interventions and weight loss will lead to a clinical benefit including reduced cardiovascular morbidity and mortality.

  10. Drug Resistant Hypertension - No SIMPLE Way Out

    OpenAIRE

    Janusz Skrzypecki; Marcin Ufnal

    2015-01-01

    Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal dene...

  11. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. A. Sulimov

    2013-01-01

    Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  12. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    OpenAIRE

    V. A. Sulimov; A. V. Rodionov; A. A. Svetankova; I. E. Deneka

    2015-01-01

    A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  13. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. A. Sulimov

    2015-09-01

    Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  14. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  15. Genetics Home Reference: type A insulin resistance syndrome

    Science.gov (United States)

    ... Conditions Type A insulin resistance syndrome Type A insulin resistance syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Type A insulin resistance syndrome is a rare disorder characterized by severe ...

  16. Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

    International Nuclear Information System (INIS)

    Naidoo, C.

    1986-01-01

    Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

  17. Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo, C

    1986-01-01

    Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

  18. Clinical approach in treatment of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Jennifer Frank

    2009-07-01

    Full Text Available Jennifer Frank, David SommerfeldUniversity of Wisconsin School of Medicine and Public Health, Department of Family Medicine, Appleton, WI, USAAbstract: Resistant hypertension, defined as failure to achieve target blood pressure despite the use of optimal or maximum doses of at least 3 agents, one of which is a diuretic, or requiring 4 or more medications to achieve blood pressure goal, is likely to affect up to 20% of all patients with hypertension. Apparent resistant hypertension may be caused by medication nonadherence, substances that either interfere with antihypertensive mediations or cause blood pressure elevation, and under- or inappropriate medication treatment. Certain patient characteristics are associated with the presence of resistant hypertension and include chronic kidney disease, diabetes, obesity, and presence of end-organ damage (microalbuminuria, retinopathy, left-ventricular hypertrophy. Secondary causes of resistant hypertension are not uncommon and include obstructive sleep apnea, chronic kidney disease, primary aldosteronism, renal artery stenosis, pheochromocytoma, and Cushing’s disease. Initial medication management usually includes adding or increasing the dose of a diuretic, which is effective in lowering the blood pressure of a large number of patients with resistant hypertension. Additional management options include maximizing lifestyle modification, combination therapy of antihypertensive agents depending on individual patient characteristics, adding less-commonly used fourth- or fifth-line antihypertensive agents, and referral to a hypertension specialist.Keywords: resistant hypertension, blood pressure, diuretic

  19. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

    2013-01-01

    Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.......Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

  20. Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

    Science.gov (United States)

    Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

    2017-01-01

    Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

  1. Insulin resistance in porphyria cutanea tarda.

    Science.gov (United States)

    Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

    1989-06-01

    It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

  2. Selective insulin resistance in hepatocyte senescence

    International Nuclear Information System (INIS)

    Aravinthan, Aloysious; Challis, Benjamin; Shannon, Nicholas; Hoare, Matthew; Heaney, Judith; Alexander, Graeme J.M.

    2015-01-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance

  3. Selective insulin resistance in hepatocyte senescence

    Energy Technology Data Exchange (ETDEWEB)

    Aravinthan, Aloysious [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Challis, Benjamin [Institute of Metabolic Sciences, University of Cambridge, Cambridge (United Kingdom); Shannon, Nicholas [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Hoare, Matthew [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Heaney, Judith [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Foundation for Liver Research, Institute of Hepatology, London (United Kingdom); Alexander, Graeme J.M., E-mail: gja1000@doctors.org.uk [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom)

    2015-02-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.

  4. Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

    International Nuclear Information System (INIS)

    Kahn, S.H.; Fazal, N.; Yasir, M.; Asif, N.; Rafi, T.

    2017-01-01

    To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology: Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results: Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism. (author)

  5. The origins and drivers of insulin resistance.

    Science.gov (United States)

    Johnson, Andrew M F; Olefsky, Jerrold M

    2013-02-14

    Obesity-induced insulin resistance is the major determinant of metabolic syndrome, which precedes the development of type 2 diabetes mellitus and is thus the driving force behind the emerging diabetes epidemic. The precise causes of insulin resistance are varied, and the relative importance of each is a matter of ongoing research. Here, we offer a Perspective on the heterogeneous etiology of insulin resistance, focusing in particular on the role of inflammation, lipid metabolism, and the gastrointestinal microbiota. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Insulin resistance and improvements in signal transduction.

    Science.gov (United States)

    Musi, Nicolas; Goodyear, Laurie J

    2006-02-01

    Type 2 diabetes and obesity are common metabolic disorders characterized by resistance to the actions of insulin to stimulate skeletal muscle glucose disposal. Insulin-resistant muscle has defects at several steps of the insulin-signaling pathway, including decreases in insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. One approach to increase muscle glucose disposal is to reverse/improve these insulin-signaling defects. Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity. In contrast, physical training and metformin improve whole-body glucose disposal but have minimal effects on proximal insulin-signaling steps. A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs). A different strategy to increase muscle glucose disposal is by stimulating insulin-independent glucose transport. AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge and becomes activated in situations of energy consumption, such as muscle contraction. Several studies have shown that pharmacologic activation of AMPK increases glucose transport in muscle, independent of the actions of insulin. AMPK activation is also involved in the mechanism of action of metformin and adiponectin. Moreover, in the hypothalamus, AMPK regulates appetite and body weight. The effect of AMPK to stimulate muscle glucose disposal and to control appetite makes it an important pharmacologic target for the treatment of type 2 diabetes and obesity.

  7. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

    2003-01-01

    BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake......, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS......: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION...

  8. Prevalence and determinants of resistant hypertension among ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research ... Prevalence and determinants of resistant hypertension among hypertensive patients attending a cardiology clinic in ... Obese patients and those suffering from diabetes mellitus, ischemic heart ... By Country · List All Titles · Free To Read Titles This Journal is Open Access.

  9. Role of mitochondrial function in insulin resistance

    NARCIS (Netherlands)

    Brands, Myrte; Verhoeven, Arthur J.; Serlie, Mireille J.

    2012-01-01

    The obesity pandemic increases the prevalence of type 2 diabetes (DM2).DM2 develops when pancreatic β-cells fail and cannot compensate for the decrease in insulin sensitivity. How excessive caloric intake and weight gain cause insulin resistance has not completely been elucidated.Skeletal muscle is

  10. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Storgaard, Heidi; Holst, Jens Juul

    2015-01-01

    BACKGROUND: Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies...... with healthy control subjects. This supports that psoriasis may be a prediabetic condition....

  11. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  12. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    olayemitoyin

    Alzheimer's disease (CBS 2012), dementia (Health news 2012) and ... the effects of coffee on insulin resistance and glucose tolerance as ..... mortality among patients with type 2 diabetes. ... transporter family: Structure, function and tissue-.

  13. Insulin resistance in obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Monica Cristina dos Santos Romualdo

    2014-11-01

    Conclusion: The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood.

  14. Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Marko Kostovski

    2018-03-01

    CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

  15. Drug Resistant Hypertension - No SIMPLE Way Out

    Directory of Open Access Journals (Sweden)

    Janusz Skrzypecki

    2015-02-01

    Full Text Available Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3, the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal denervation. In order to identify causes of inconsistent results in renal denervation studies we look at basic science support for renal denervation and at designs of clinical trials.

  16. Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders

    Directory of Open Access Journals (Sweden)

    A. Janus

    2016-01-01

    Full Text Available Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes.

  17. Recent advances in the management of resistant hypertension

    OpenAIRE

    Manolis, Athanasios J.; Kallistratos, Manolis S.; Doumas, Michalis; Pagoni, Stamatina; Poulimenos, Leonidas

    2015-01-01

    And suddenly, following the preliminary results of renal denervation and carotid baroreceptor stimulation, a big interest in resistant hypertension rose, and all interventionists, many of them with no previous experience with hypertension, fell in love with hypertension and especially resistant hypertension. In the European Society of Hypertension/International Society of Hypertension (ESH/ISH) 2014 Joint Hypertension meeting in Athens, there were no more than four to five sessions related to...

  18. Insulin resistance: vascular function and exercise

    Directory of Open Access Journals (Sweden)

    Moon-Hyon Hwang

    2016-09-01

    Full Text Available Insulin resistance associated with metabolic syndrome and Type 2 diabetes mellitus is an epidemic metabolic disorder, which increases the risk of cardiovascular complications. Impaired vascular endothelial function is an early marker for atherosclerosis, which causes cardiovascular complications. Both experimental and clinical studies indicate that endothelial dysfunction in vasculatures occurs with insulin resistance. The associated physiological mechanisms are not fully appreciated yet, however, it seems that augmented oxidative stress, a physiological imbalance between oxidants and antioxidants, in vascular cells is a possible mechanism involved in various vascular beds with insulin resistance and hyperglycemia. Regardless of the inclusion of resistance exercise, aerobic exercise seems to be beneficial for vascular endothelial function in both large conduit and small resistance vessels in both clinical and experimental studies with insulin resistance. In clinical cases, aerobic exercise over 8 weeks with higher intensity seems more beneficial than the cases with shorter duration and lower intensity. However, more studies are needed in the future to elucidate the physiological mechanisms by which vascular endothelial function is impaired in insulin resistance and improved with aerobic exercise.

  19. The role of endoplasmic reticulum stress in hippocampal insulin resistance.

    Science.gov (United States)

    Sims-Robinson, Catrina; Bakeman, Anna; Glasser, Rebecca; Boggs, Janet; Pacut, Crystal; Feldman, Eva L

    2016-03-01

    Metabolic syndrome, which includes hypertension, hyperglycemia, obesity, insulin resistance, and dyslipidemia, has a negative impact on cognitive health. Endoplasmic reticulum (ER) stress is activated during metabolic syndrome, however it is not known which factor associated with metabolic syndrome contributes to this stress. ER stress has been reported to play a role in the development of insulin resistance in peripheral tissues. The role of ER stress in the development of insulin resistance in hippocampal neurons is not known. In the current study, we investigated ER stress in the hippocampus of 3 different mouse models of metabolic syndrome: the C57BL6 mouse on a high fat (HF) diet; apolipoprotein E, leptin, and apolipoprotein B-48 deficient (ApoE 3KO) mice; and the low density lipoprotein receptor, leptin, and apolipoprotein B-48 deficient (LDLR 3KO) mice. We demonstrate that ER stress is activated in the hippocampus of HF mice, and for the first time, in ApoE 3KO mice, but not LDLR 3KO mice. The HF and ApoE 3KO mice are hyperglycemic; however, the LDLR 3KO mice have normal glycemia. This suggests that hyperglycemia may play a role in the activation of ER stress in the hippocampus. Similarly, we also demonstrate that impaired insulin signaling is only present in the HF and ApoE 3KO mice, which suggests that ER stress may play a role in insulin resistance in the hippocampus. To confirm this we pharmacologically induced ER stress with thapsigargin in human hippocampal neurons. We demonstrate for the first time that thapsigargin leads to ER stress and impaired insulin signaling in human hippocampal neurons. Our results may provide a potential mechanism that links metabolic syndrome and cognitive health. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Recognition and Management of Resistant Hypertension.

    Science.gov (United States)

    Braam, Branko; Taler, Sandra J; Rahman, Mahboob; Fillaus, Jennifer A; Greco, Barbara A; Forman, John P; Reisin, Efrain; Cohen, Debbie L; Saklayen, Mohammad G; Hedayati, S Susan

    2017-03-07

    Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events. Copyright © 2017 by the American Society of Nephrology.

  1. Apparent and true resistant hypertension: definition, prevalence and outcomes.

    Science.gov (United States)

    Judd, E; Calhoun, D A

    2014-08-01

    Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of > or =3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires > or =4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. This classically defined resistant group consists of patients with true resistant hypertension, controlled resistant hypertension and pseudo-resistant hypertension. In studies where pseudo-resistant hypertension cannot be excluded (for example, 24-h ambulatory BP not obtained), the term apparent resistant hypertension has been used to identify 'apparent' lack of control on > or =3 medications. Large, well-designed studies have recently reported the prevalence of resistant hypertension. Pooling prevalence data from these studies and others within North America and Europe with a combined sample size of >600,000 hypertensive participants, the prevalence of resistant hypertension is 14.8% of treated hypertensive patients and 12.5% of all hypertensives. However, the prevalence of true resistant hypertension, defined as uncontrolled both by office and 24-h ambulatory BP monitoring with confirmed medication adherence, may be more meaningful in terms of identifying risk and estimating benefit from newer therapies like renal denervation. Rates of cardiovascular events and mortality follow mean 24-h ambulatory BPs in patients with resistant hypertension, and true resistant hypertension represents the highest risk. The prevalence of true resistant hypertension has not been directly measured in large trials; however, combined data from smaller studies suggest that true resistant hypertension is present in half of the patients with resistant hypertension who are uncontrolled in the office. Our pooled analysis shows prevalence rates of 10.1% and 7.9% for uncontrolled resistant hypertension among

  2. Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.

    Science.gov (United States)

    Qiu, Jian; Bosch, Martha A; Meza, Cecilia; Navarro, Uyen-Vy; Nestor, Casey C; Wagner, Edward J; Rønnekleiv, Oline K; Kelly, Martin J

    2018-02-01

    Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation. Copyright © 2018 Endocrine Society.

  3. Insulin resistance in obese children and adolescents.

    Science.gov (United States)

    Romualdo, Monica Cristina dos Santos; Nóbrega, Fernando José de; Escrivão, Maria Arlete Meil Schimith

    2014-01-01

    To evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents. Retrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests. Insulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p=0.044), waist circumference measurement (p=0.030), and the set of clinical and metabolic (p=0.000) alterations. Insulin-resistant individuals had higher mean age (p=0.000), body mass index (BMI; p=0.000), abdominal circumference (p=0.000), median triglycerides (p=0.001), total cholesterol (p≤0.042), and low-density lipoprotein cholesterol (LDL-C; p≤0.027); and lower HDL-C levels (p=0.005). There was an increase in mean BMI (p=0.000), abdominal circumference (p=0.000), and median triglycerides (p=0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p=0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA-IR index (p=0.000). The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. Skeletal Muscle Insulin Resistance in Endocrine Disease

    Directory of Open Access Journals (Sweden)

    Melpomeni Peppa

    2010-01-01

    Full Text Available We summarize the existing literature data concerning the involvement of skeletal muscle (SM in whole body glucose homeostasis and the contribution of SM insulin resistance (IR to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS, adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

  5. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

    Review Article. ,. Molecular ... This review discusses recent advances in understanding of the structure and ... insulin action from receptor to the alteration of blood glucose. Hence, in ... the first protein to have its amino acid sequence determined;2 ... an integral membrane glycoprotein composed of two subunits, a and 13 ...

  6. Mechanism of insulin resistance in normal pregnancy.

    Science.gov (United States)

    Hodson, K; Man, C Dalla; Smith, F E; Thelwall, P E; Cobelli, C; Robson, S C; Taylor, R

    2013-08-01

    Normal pregnancy is associated with insulin resistance although the mechanism is not understood. Increased intramyocellular lipid is closely associated with the insulin resistance of type 2 diabetes and obesity, and the aim of this study was to determine whether this was so for the physiological insulin resistance of pregnancy. Eleven primiparous healthy pregnant women (age: 27-39 years, body mass index 24.0±3.1 kg/m2) and no personal or family history of diabetes underwent magnetic resonance studies to quantify intramyocellular lipid, plasma lipid fractions, and insulin sensitivity. The meal-related insulin sensitivity index was considerably lower in pregnancy (45.6±9.9 vs. 193.0±26.1; 10(-4) dl/kg/min per pmol/l, p=0.0002). Fasting plasma triglyceride levels were elevated 3-fold during pregnancy (2.3±0.2 vs. 0.8±0.1 mmol/l, pinsulin resistance is distinct from that underlying type 2 diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

  8. Refractory versus resistant hypertension: Novel distinctive phenotypes

    Science.gov (United States)

    Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

    2017-01-01

    Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

  9. RESISTANT HYPERTENSION IN A PATIENT WITH METABOLIC SYNDROME

    OpenAIRE

    O. M. Drapkina; J. S. Sibgatullina

    2016-01-01

    Clinical case of resistant hypertension in a patient with metabolic syndrome is presented. Features of hypertension in metabolic syndrome and features of metabolic syndrome in women of pre- and postmenopausal age are also considered. Understanding the features of metabolic syndrome in women, as well as features of hypertension and metabolic syndrome will improve the results of treatment in patients with resistant hypertension.

  10. Molecular mechanisms of insulin resistance | Pillay | South African ...

    African Journals Online (AJOL)

    This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin ...

  11. Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients.

    Science.gov (United States)

    Canbakan, Mustafa; Sahin, Gülizar Manga

    2007-01-01

    Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

  12. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  13. Efeitos da suplementação de potássio via sal de cozinha sobre a pressão arterial e a resistência à insulina em pacientes obesos hipertensos em uso de diuréticos Effects of potassium supplementation by salt on arterial blood pressure and insulin resistance in hypertensive obese patients on diuretic therapy

    Directory of Open Access Journals (Sweden)

    Maria Alice de Gouveia Pereira

    2005-02-01

    Full Text Available OBJETIVO: Avaliar os efeitos da suplementação de potássio, por intermédio do sal de cozinha contendo cloreto de potássio, associada à dieta hipocalórica e à atividade física aeróbica, sobre a pressão arterial e índices de resistência à insulina em pacientes hipertensos com obesidade abdominal. MÉTODOS: Estudo prospectivo duplo-cego, randomizado, em 22 pacientes hipertensos com excesso de peso (índice de massa corporal >27kg/m² e controle insatisfatório da pressão arterial durante o uso de diuréticos pressão arterial sistólica >140 e 90 e OBJECTIVE: The objectives of the present study were to evaluate the effects of oral potassium supplementation, associated with a hypocaloric diet and aerobic exercises, on plasma potassium levels, blood pressure and insulin resistance, in centrally obese, not well controlled hypertensive patients on diuretic therapy; waist to hip ratio >0.85 in women, and >0.95 in men; systolic blood pressure >140mmHg and 90mmHg and <105mmHg. METHODS: This was a prospective double-blind randomized study including 22 patients divided in 2 groups: sodium chloride n=10, and potassium chloride n=12. For 12 weeks, each group received cooking salt containing, either 100% sodium chloride, or 50% sodium chloride and 50% potassium chloride. All patients were submitted to a hypocaloric diet and advised to increase their physical activity; a 40-minute walk three times a week. Before and after the study period, all patients were submitted to determinations of body mass index, body composition, waist circumference, sodium and potassium urinary excretions, sodium and potassium serum levels, 24h ambulatory blood pressure monitoring, oral glucose tolerance test with serum insulin measurements at fasting and 120 minutes after glucose load, and serum lipid profile. RESULTS: In both groups, no changes were observed in serum sodium and potassium levels, in blood glucose and insulin levels, insulin resistance indexes and serum

  14. Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

    Science.gov (United States)

    Roberts, Christian K.; Hevener, Andrea L.; Barnard, R. James

    2014-01-01

    Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity. PMID:23720280

  15. Role of the Kidneys in Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Z. Khawaja

    2011-01-01

    Full Text Available Resistant hypertension is a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease in a patient who adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic. The kidneys play a critical role in long-term regulation of blood pressure. Blunted pressure natriuresis, with resultant increase in extracellular fluid volume, is an important cause of resistant hypertension. Activation of the renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity and increased sodium reabsorption are important renal mechanisms. Successful treatment requires identification and reversal of lifestyle factors or drugs contributing to treatment resistance, diagnosis and appropriate treatment of secondary causes of hypertension, use of effective multidrug regimens and optimization of diuretic therapy. Since inappropriate renal salt retention underlies most cases of drug-resistant hypertension, the therapeutic focus should be on improving salt depleting therapy by assessing and, if necessary, reducing dietary salt intake, optimizing diuretic therapy, and adding a mineralocorticoid antagonist if there are no contraindications.

  16. Resistant Hypertension : consequences and treatment options

    NARCIS (Netherlands)

    de Beus, E.

    2017-01-01

    Resistant hypertension, uncontrolled blood pressure despite use of ≥3 antihypertensives including a diuretic or use of ≥4 antihypertensives regardless of blood pressure (BP), was studied. In this thesis, 1/3 of patients with chronic kidney disease, including kidney transplant patients, is shown to

  17. Hippocampal insulin resistance and cognitive dysfunction

    NARCIS (Netherlands)

    Biessels, Geert Jan; Reagan, Lawrence P.

    2015-01-01

    Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as

  18. Mitochondrial adaptations in insulin resistant muscle

    NARCIS (Netherlands)

    Broek, van den N.M.A.

    2010-01-01

    Diabetes has reached epidemic proportions worldwide. Type 2 diabetes (T2D) accounts for about 90% of all diabetes cases and is characterized by insulin resistance (IR) in major metabolic tissues. The dramatic rise in T2D is associated with the increased occurrence of obesity and excessive ectopic

  19. Insulin resistance induced by antiretroviral drugs: Current ...

    African Journals Online (AJOL)

    Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients with AIDS, but it has also increased the incidence of various metabolic disorders, in particular insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often accompanied by frank type 2 ...

  20. Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor gamma agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X.

    Science.gov (United States)

    Velliquette, Rodney A; Friedman, Jacob E; Shao, J; Zhang, Bei B; Ernsberger, Paul

    2005-07-01

    Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as metabolic syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroxisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg x min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold excess fasting insulin and increased insulin AUC (6300 ng x min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with metabolic syndrome but via distinct mechanisms.

  1. Determinación del índice de resistencia a la insulina mediante homa y su relación con el riesgo de hipertensión inducida por el embarazo Insulin resistance index assessment by homa and its relation with the risk of pregnancy induced hypertension

    Directory of Open Access Journals (Sweden)

    Jesús Sierra-Laguado

    Full Text Available Objetivo: investigar si el grado de resistencia a la insulina determinado por el índice HOMA, predice de manera temprana el desarrollo de hipertensión inducida por el embarazo en gestantes colombianas. Diseño-métodos: se realizó un estudio de casos y controles anidado en una cohorte prospectiva de 438 mujeres primigestantes, normotensas y con edad gestacional menor de 30 semanas. Se determinó el índice HOMA a partir de la medición de glucemia e insulina plasmática en ayunas, por métodos de glucosa oxidasa y quimioluminiscencia, respectivamente. Resultados: veintitrés mujeres desarrollaron hipertensión inducida por el embarazo (5,25%. Se seleccionaron de forma aleatoria dos embarazadas normotensas como controles por cada caso, pareadas por edad materna y gestacional al momento de su inclusión. Las mujeres que posteriormente desarrollaron hipertensión inducida por el embarazo presentaron mayores niveles de HOMA (1,48 ± 0,98 vs. 0,96 ± 0,70, pObjective: to assess whether insulin resistance determined by homeostatic model assessment (HOMA is an early predictor of the development of pregnancy induced hypertension in Colombian pregnant women. Methods: we conducted a nested case control study in a prospective cohort of four hundred and thirty eigth normotensive primigravidae women, with gestational age < 30 weeks. The HOMA was calculated using fasting plasma concentrations of glucose and insulin, determined by glucose-oxidase and chemoluminiscence methods, respectively. Results: twenty-three pregnant women developed pregnancy induced hypertension (5.25%. Two normotensive pregnant women were selected as controls for each case, matched by gestational and maternal age at enrollment. The women who subsequently developed pregnancy induced hypertension had higher levels of HOMA (1.48 ± 0.98 vs 0.96 ± 0.70, p<0.001, which was associated with an increased risk of developing pregnancy induced hypertension (OR: 3.8, IC95%: 1.1-12.8 p=0

  2. Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

    OpenAIRE

    Walker, A P; Flint, D J

    1983-01-01

    Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

  3. Adipokines mediate inflammation and insulin resistance

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Pessin

    2013-06-01

    Full Text Available For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secrete various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

  4. Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

    Science.gov (United States)

    Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

    2012-08-01

    Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

  5. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy

    Directory of Open Access Journals (Sweden)

    Rebecca Oelkrug

    2017-10-01

    Conclusions: Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension.

  6. Relationship between serum insulin level and age and sex in 980 patients with essential hypertension

    International Nuclear Information System (INIS)

    Cai Jianlin; Ji Naijun; Mei Yubin; Wang Chengyao; Fan Bifu; Chen Donghai; Guan Li; Tong Lijun; Li Fuyuan; Gao Meiying

    2004-01-01

    Objective: To investigate the change of serum insulin level in essential hypertension patients and its relationship with age and sex. Methods: The levels of serum insulin were determined with radioimmunoassay in 980 essential hypertension patients and 120 controls. Results: The levels of serum insulin in the essential hypertension patients were significantly higher than those in the controls (t=4.280, P<0.01). However, there were no significant differences among the levels in different sex and age groups. The same held true for women before and after menopause as well as different stages of hypertension. Conclusion: The average serum insulin level in EH patients was significantly higher than the level in controls, and had positive correlation to mean arterial pressure. But no significant differences were found among different sex and age groups, so serum insulin could be a new independent risk factor of essential hypertension

  7. MODELS OF INSULIN RESISTANCE AND HEART FAILURE

    Science.gov (United States)

    Velez, Mauricio; Kohli, Smita; Sabbah, Hani N.

    2013-01-01

    The incidence of heart failure (HF) and diabetes mellitus is rapidly increasing and is associated with poor prognosis. In spite of the advances in therapy, HF remains a major health problem with high morbidity and mortality. When HF and diabetes coexist, clinical outcomes are significantly worse. The relationship between these two conditions has been studied in various experimental models. However, the mechanisms for this interrelationship are complex, incompletely understood, and have become a matter of considerable clinical and research interest. There are only few animal models that manifest both HF and diabetes. However, the translation of results from these models to human disease is limited and new models are needed to expand our current understanding of this clinical interaction. In this review, we discuss mechanisms of insulin signaling and insulin resistance, the clinical association between insulin resistance and HF and its proposed pathophysiologic mechanisms. Finally, we discuss available animal models of insulin resistance and HF and propose requirements for future new models. PMID:23456447

  8. Fatty Acids, Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Peter Arner

    2015-04-01

    Full Text Available Objective: Although elevated free fatty acid (FFA levels in obesity have been considered to be of importance for insulin resistance, a recent meta-analysis suggested normal FFA levels in obese subjects. We investigated fasting circulating FFA and glycerol levels in a large cohort of non-obese and obese subjects. Methods: Subjects recruited for a study on obesity genetics were investigated in the morning after an overnight fast (n = 3,888. Serum FFA (n = 3,306, plasma glycerol (n = 3,776, and insulin sensitivity index (HOMA-IR,n = 3,469 were determined. Obesity was defined as BMI ≥ 30 kg/m2 and insulin resistance as HOMA-IR ≥ 2.21. Results: In obese subjects, circulating FFA and glycerol levels were higher than in non-obese individuals (by 26% and 47%, respectively; both p Conclusion: Circulating FFA and glycerol levels are markedly elevated in obesity but only marginally influenced by insulin resistance and type 2 diabetes. Whether these differences persist during diurnal variations in circulating FFA/glycerol, remains to be established.

  9. Insulin resistance alters islet morphology in nondiabetic humans

    DEFF Research Database (Denmark)

    Mezza, Teresa; Muscogiuri, Giovanna; Sorice, Gian Pio

    2014-01-01

    Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects...... pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared...... insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell-to-α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from...

  10. Renal denervation for resistant hypertension and beyond.

    Science.gov (United States)

    Laffin, Luke J; Bakris, George L

    2015-03-01

    Despite the availability of more than 125 approved antihypertensive medications, 36 million (48%) of 75 million people with hypertension, including 16 million treated with antihypertensive medications in the United States, do not achieve guideline blood pressure goals known to reduce cardiovascular morbidity and mortality and progression of kidney disease; 3% to 6% of these 75 million hypertensive individuals are estimated to have resistant hypertension. A major contributing factor for poor blood pressure control, besides inadequate diuretic therapy, is failure of antihypertensive agents to inhibit the sympathetic nervous system effectively. Consequently, alternative device-driven approaches have been developed. Recent technical advances targeting renal sympathetic nerves, that is, renal denervation therapy, are the focus of more invasive therapies to treat resistant hypertension. Encouraging results from the SYMPLICITY HTN-2 trial, regarding efficacy and safety of renal denervation therapy, were countered by disappointing efficacy results of SYMPLICITY HTN-3. Reasons for these divergent results and the future of the field are discussed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  11. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

    Science.gov (United States)

    Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

    2017-12-01

    Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Blueberries? Impact on Insulin Resistance and Glucose Intolerance

    OpenAIRE

    Stull, April J.

    2016-01-01

    Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by hom...

  13. Insulin resistance and polycystic ovary syndrome.

    Science.gov (United States)

    Galluzzo, Aldo; Amato, Marco Calogero; Giordano, Carla

    2008-09-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in humans, affecting approximately 7-8% of women of reproductive age. Despite the criteria adopted, PCOS is considered to be a predominantly hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin sensitivity is not mandatory. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Acknowledging the strong impact of insulin-resistance in the genesis of PCOS could be helpful not only to make the diagnosis more robust, but also for conferring better cardiovascular risk prevention. Several current studies support a strong recommendation that women with PCOS should undergo comprehensive evaluation for the metabolic syndrome and recognized cardiovascular risk factors, and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many of these women do not lose weight easily. Insulin-sensitizing drugs are discussed as a promising and unique therapeutic option for the chronic treatment of PCOS.

  14. Down-regulation of the miR-543 alleviates insulin resistance through targeting the SIRT1.

    Science.gov (United States)

    Hu, Xiaojing; Chi, Liyi; Zhang, Wentao; Bai, Tiao; Zhao, Wei; Feng, Zhanbin; Tian, Hongyan

    2015-12-25

    Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin-resistant HepG2 cells induced by TNF-α. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR-543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3β. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Insulin resistance in polycystic ovary syndrome

    OpenAIRE

    Hutchison, Samantha Kate

    2017-01-01

    Polycystic ovary syndrome (PCOS) affects 8-18% of women, presenting a major public health and economic burden. Women with PCOS have insulin resistance (IR) independent of obesity. IR has an integral aetiological role in the reproductive and metabolic consequences of PCOS including obesity, type 2 diabetes (diabetes) and cardiovascular risk factors. Excess weight exacerbates IR and increases PCOS severity. PCOS combined with obesity presents a useful model to study IR before confounding hyperg...

  16. Mitochondrial adaptations in insulin resistant muscle

    OpenAIRE

    Broek, van den, N.M.A.

    2010-01-01

    Diabetes has reached epidemic proportions worldwide. Type 2 diabetes (T2D) accounts for about 90% of all diabetes cases and is characterized by insulin resistance (IR) in major metabolic tissues. The dramatic rise in T2D is associated with the increased occurrence of obesity and excessive ectopic lipid accumulation, in particular in skeletal muscle, due to excessive caloric intake and decreased physical activity. However, the exact processes leading to IR remain unresolved. One of the leading...

  17. Molecular Mechanisms of Insulin Resistance in Chronic Kidney Disease

    Science.gov (United States)

    Thomas, Sandhya S.; Zhang, Liping; Mitch, William E.

    2015-01-01

    Insulin resistance refers to reduced sensitivity of organs to insulin-initiated biologic processes that result in metabolic defects. Insulin resistance is common in patients with end-stage renal disease but also occurs in patients with chronic kidney disease (CKD), even when the serum creatinine is minimally increased. Following insulin binding to its receptor, auto-phosphorylation of the insulin receptor is followed by kinase reactions that phosphorylate insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt. In fact, low levels of Akt phosphorylation (p-Akt) identifies the presence of the insulin resistance that leads to metabolic defects in insulin-initiated metabolism of glucose, lipids and muscle proteins. Besides CKD, other complex conditions (e.g., inflammation, oxidative stress, metabolic acidosis, aging and excess angiotensin II) reduce p-Akt resulting in insulin resistance. Insulin resistance in each of these conditions is due to activation of different, E3 ubiquitin ligases which specifically conjugate ubiquitin to IRS-1 marking it for degradation in the ubiquitin-proteasome system (UPS). Consequently, IRS-1 degradation suppresses insulin-induced intracellular signaling, causing insulin resistance. Understanding mechanisms of insulin resistance could lead to therapeutic strategies that improve the metabolism of patients with CKD. PMID:26444029

  18. Common Secondary Causes of Resistant Hypertension and Rational for Treatment

    OpenAIRE

    Faselis, Charles; Doumas, Michael; Papademetriou, Vasilios

    2011-01-01

    Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of ...

  19. Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

    International Nuclear Information System (INIS)

    Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

    1989-01-01

    Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

  20. Resistant Hypertension and Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Akram Khan

    2013-01-01

    Full Text Available Hypertension (HTN is a modifiable, highly prevalent risk factor for cardiovascular morbidity and renal dysfunction worldwide. In the United States, HTN affects one in three adults, contributes to one out of every seven deaths and to nearly half of all cardiovascular disease-related deaths. HTN is considered resistant when the blood pressure remains above goal despite lifestyle modification and administration of three antihypertensive agents of different classes including a diuretic. Large population-based studies have suggested that obstructive sleep apnea (OSA is a risk factor for resistant HTN. The mechanism proposed is a pattern of intermittent hypoxia associated with hyperaldosteronism, increased sympathetic tone, endothelial dysfunction, and inflammation. In this review we discuss the association between OSA and resistant HTN, the physiologic mechanisms linking OSA with resistant HTN, and the effect of continuous positive airway pressure therapy (CPAP on blood pressure in patients with resistant HTN. While the reduction in blood pressure with CPAP is usually modest in patients with OSA, a decrease of only a few mmHg in blood pressure can significantly reduce cardiovascular risk. Patients presenting to a center specializing in management of hypertension should be screened and treated for OSA as a potentially modifiable risk factor.

  1. Insulin Resistance Induced by Short term Fructose Feeding may not ...

    African Journals Online (AJOL)

    Fructose feeding causes insulin resistance and invariably Non-Insulin Dependent Diabetes Mellitus (NIDDM) in rats and genetically predisposed humans. The effect of insulin resistance induced by short term fructose feeding on fertility in female rats was investigated using the following parameters: oestrous phase and ...

  2. Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

    Science.gov (United States)

    ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

    2015-12-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

  3. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

    Directory of Open Access Journals (Sweden)

    Rodrigo Vanerson Passos Neves

    2016-01-01

    Full Text Available Abstract Background: Resistance training (RT has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH. Objective: This study examined the effects of two RT protocols (vertical ladder climbing, performed at different overloads of maximal weight carried (MWC, on blood pressure (BP and muscle strength of spontaneously hypertensive rats (SHR with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBPENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP were divided into 4 groups: sedentary (SED-WKY and SHR (SED-SHR; RT1-SHR training relative to body weight (~40% of MWC; and RT2-SHR training relative to MWC test (~70% of MWC. Systolic BP and heart rate (HR were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05, whereas SBP of the SED-SHR group increased by 19 mmHg (p 0.05. Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

  4. PEDF-induced alteration of metabolism leading to insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arunasalam M; Dass, Crispin R

    2015-02-05

    Pigment epithelium-derived factor (PEDF) is an anti-angiogenic, immunomodulatory, and neurotrophic serine protease inhibitor protein. PEDF is evolving as a novel metabolic regulatory protein that plays a causal role in insulin resistance. Insulin resistance is the central pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, polycystic ovarian disease, and metabolic syndrome, and PEDF is associated with them. The current evidence suggests that PEDF administration to animals induces insulin resistance, whereas neutralisation improves insulin sensitivity. Inflammation, lipolytic free fatty acid mobilisation, and mitochondrial dysfunction are the proposed mechanism of PEDF-mediated insulin resistance. This review summarises the probable mechanisms adopted by PEDF to induce insulin resistance, and identifies PEDF as a potential therapeutic target in ameliorating insulin resistance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Apparent and true resistant hypertension: definition, prevalence and outcomes

    OpenAIRE

    Judd, E; Calhoun, DA

    2014-01-01

    Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires ≥4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. This classically defined resistant group consists of patients with true resistant hypertension, controlled resistant hy...

  6. Renal sympathetic denervation for resistant hypertension.

    Science.gov (United States)

    Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

    2013-05-01

    Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  7. A Complicated Case of Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Mauro Chiarito

    2017-10-01

    Full Text Available A 47-year-old woman presented with a history of resistant arterial hypertension, associated with disabling headache. She was subjected to an enormous number of tests in order to identify an underlying cause of secondary hypertension, such as pheochromocytoma or Cushing syndrome, but all the most common causes of secondary hypertension were investigated and gradually excluded. Factitious use of amphetamine or cocaine was excluded, and therapy compliance was verified by witnessed ingestion of drug therapy, in order to rule out Munchausen syndrome. The patient underwent a first transcatheter renal denervation (RDN with poor effect on blood pressure (BP at long term follow up. Because of extremely poor control of BP values, a second RDN was performed two years later, again with inadequate long term efficacy. Despite an uncontrollable pre-procedural BP, RDN had an excessive BP lowering effect in this patient, but only for few months. In conclusion, a definitive diagnosis was not performed in our patient, despite an extremely deepened examination of the most common cause of refractory hypertension.

  8. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin resistant phenotypes

    DEFF Research Database (Denmark)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas

    2013-01-01

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilizati...

  9. Tau deletion promotes brain insulin resistance.

    Science.gov (United States)

    Marciniak, Elodie; Leboucher, Antoine; Caron, Emilie; Ahmed, Tariq; Tailleux, Anne; Dumont, Julie; Issad, Tarik; Gerhardt, Ellen; Pagesy, Patrick; Vileno, Margaux; Bournonville, Clément; Hamdane, Malika; Bantubungi, Kadiombo; Lancel, Steve; Demeyer, Dominique; Eddarkaoui, Sabiha; Vallez, Emmanuelle; Vieau, Didier; Humez, Sandrine; Faivre, Emilie; Grenier-Boley, Benjamin; Outeiro, Tiago F; Staels, Bart; Amouyel, Philippe; Balschun, Detlef; Buee, Luc; Blum, David

    2017-08-07

    The molecular pathways underlying tau pathology-induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer's disease patients. © 2017 Marciniak et al.

  10. [Therapy-resistant and therapy-refractory arterial hypertension].

    Science.gov (United States)

    Wallbach, M; Koziolek, M J

    2018-05-02

    Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

  11. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul S

    2016-01-01

    transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle....

  12. Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

    2018-03-14

    The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

  13. Renal denervation for resistant hypertension: yes.

    Science.gov (United States)

    Boschetti, Enrico; Alrashdi, Yahya; Schillaci, Giuseppe

    2016-06-01

    Sympathetic overactivity may have a role in triggering and maintaining resistant hypertension, and catheter-based renal denervation (RDN) has emerged as a promising treatment in refractory hypertension. Recently, the results of the Symplicity HTN-3, the first randomized, sham-controlled trial, failed to confirm the previously reported BP-lowering effects of RDN, although definitive conclusions cannot be drawn due to a number of study limitations. Consequently, although some centers halted their RDN programs, research continues and both the concept of denervation and treatment strategies are being redefined. A new generation of sham-controlled trials is currently underway with the aim of detecting which patients are expected to achieve the most beneficial effect from RDN. In this article, we examine the current data on RDN and discuss some insights and future opportunities.

  14. Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

    Science.gov (United States)

    Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

    2015-01-01

    Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

  15. Adipose Tissue Insulin Resistance in Gestational Diabetes.

    Science.gov (United States)

    Tumurbaatar, Batbayar; Poole, Aaron T; Olson, Gayle; Makhlouf, Michel; Sallam, Hanaa S; Thukuntla, Shwetha; Kankanala, Sucharitha; Ekhaese, Obos; Gomez, Guillermo; Chandalia, Manisha; Abate, Nicola

    2017-03-01

    Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC] glucose ). Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

  16. Obesidade abdominal, resistência à insulina e hipertensão: impacto sobre a massa e a função do ventrículo esquerdo em mulheres Abdominal obesity, insulin resistance and hypertension: impact on left ventricular mass and function in women

    Directory of Open Access Journals (Sweden)

    Eliana A. Silva

    2007-08-01

    .05. CONCLUSION: Our results indicate an association among hypertension, central obesity and left ventricular hypertrophy through increases in sympathetic activity and insulin resistance.

  17. Fructose, insulin resistance, and metabolic dyslipidemia

    Directory of Open Access Journals (Sweden)

    Adeli Khosrow

    2005-02-01

    Full Text Available Abstract Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.

  18. Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

    Science.gov (United States)

    Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

    2018-02-01

    OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

  19. Retinol binding protein 4, obesity, and insulin resistance in adolescents

    Directory of Open Access Journals (Sweden)

    Ronaldi Noor

    2017-02-01

    Full Text Available Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4, secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated. Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56. We measured subjects’ body mass index (BMI and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR index. Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05. Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05. Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.

  20. Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

    DEFF Research Database (Denmark)

    de Courten, Maximilian; Ferrari, P; Schneider, M

    1993-01-01

    Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients......To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model...... [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg...

  1. Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

    Science.gov (United States)

    Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

    2017-10-01

    Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Molecular Mechanisms of Chromium in Alleviating Insulin Resistance

    Science.gov (United States)

    Hua, Yinan; Clark, Suzanne; Ren, Jun; Sreejayan, Nair

    2011-01-01

    Type 2 diabetes is often associated with obesity, dyslipidemia, and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance. PMID:22423897

  3. Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

    International Nuclear Information System (INIS)

    Salhanick, A.I.; Amatruda, J.M.

    1988-01-01

    Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

  4. Acceptance of insulin therapy: a long shot? Psychological insulin resistance in primary care

    NARCIS (Netherlands)

    Woudenberg, Y. J. C.; Lucas, C.; Latour, C.; Scholte Op Reimer, W. J. M.

    2012-01-01

    Diabet. Med. 29, 796802 (2012) Abstract Aim To explore which factors are associated with psychological insulin resistance in insulin-naive patients with Type 2 diabetes in primary care. Methods A sample of 101 insulin-naive patients with Type 2 diabetes completed self-administered questionnaires

  5. Relationship among resistance to the insulin and obesity in Zacatecas population

    International Nuclear Information System (INIS)

    Zapata R, P. G.; Badillo A, V.

    2012-10-01

    The Zacatecas State (Mexico) occupies the second national place in obesity, although the adults have a bigger incidence every time exist more minors that present this problem which can facilitate other illnesses like diabetes and hypertension. The first resistance references to the insulin were made by Himsworth in 1936, when he referred to insulin-resistant and insulin-sensitive diabetics. The resistance to the insulin, as event pathogen primary in the diabetes mellitus type 2 is derived of the obesity, what implies a subnormal biological response to the actions of the hormone in the carbohydrates, proteins and lipids metabolism. In this work was carried out a study of insulin levels for the Radioimmunoassay method in 40 patients with evident obesity and 8 patients with normal weight in order to evaluate these levels according to their age and abdominal circumference. Three correlations were made for both groups (obese and normal), the first correlation indicates the size of the waist with the insulin quantity, according to the arrangements that shows the correlation is bigger in all; what means that there is a great dependence among the size of the waist and the insulin quantity that contain. The second correlation is the age with the insulin that although is small, indicates that the age does not important for the insulin quantity that is secreted. The third and last realized correlation was of the age with the waist, and according to the results correlation also exists, but this is not significant as the first correlation. Therefore is considered existent the relationship between obesity and resistance to the insulin. (Author)

  6. Insulin resistance in brain and possible therapeutic approaches.

    Science.gov (United States)

    Cetinkalp, Sevki; Simsir, Ilgin Y; Ertek, Sibel

    2014-01-01

    Although the brain has long been considered an insulin-independent organ, recent research has shown that insulin has significant effects on the brain, where it plays a role in maintaining glucose and energy homeostasis. To avoid peripheral insulin resistance, the brain may act via hypoinsulinemic responses, maintaining glucose metabolism and insulin sensitivity within its own confines; however, brain insulin resistance may develop due to environmental factors. Insulin has two important functions in the brain: controlling food intake and regulating cognitive functions, particularly memory. Notably, defects in insulin signaling in the brain may contribute to neurodegenerative disorders. Insulin resistance may damage the cognitive system and lead to dementia states. Furthermore, inflammatory processes in the hypothalamus, where insulin receptors are expressed at high density, impair local signaling systems and cause glucose and energy metabolism disorders. Excessive caloric intake and high-fat diets initiate insulin and leptin resistance by inducing mitochondrial dysfunction and endoplasmic reticulum stress in the hypothalamus. This may lead to obesity and diabetes mellitus (DM). Exercise can enhance brain and hypothalamic insulin sensitivity, but it is the option least preferred and/or continuously practiced by the general population. Pharmacological treatments that increase brain and hypothalamic insulin sensitivity may provide new insights into the prevention of dementia disorders, obesity, and type 2 DM in the future.

  7. Peripheral nervous system insulin resistance in ob/ob mice

    Science.gov (United States)

    2013-01-01

    Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

  8. Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions

    NARCIS (Netherlands)

    Serne, EH; Gans, ROB; ter Maaten, JC; ter Wee, PM; Donker, AM; Stehouwer, CDA

    Objective: In patients with essential hypertension, defects in both the metabolic and vascular actions of insulin have been described. Impaired microvascular function, a well-established abnormality in essential hypertension, may explain part of these defects. In the present study we investigated

  9. Resistant hypertension: an approach to management in primary care

    Directory of Open Access Journals (Sweden)

    Julian P Yaxley

    2015-01-01

    Full Text Available Hypertension is widely encountered in family medicine. Despite its prevalence, many patients have uncontrolled or difficult-to-control blood pressure. Resistant hypertension is defined as hypertension that is poorly responsive to treatment and requires the use of multiple medications to achieve acceptable blood pressure ranges. It may be a consequence of secondary hypertension or have no identifiable cause. Resistant hypertension is important to recognise because it places patients at risk of end-organ damage. Primary care physicians should be aware of the therapeutic approach for hypertension when traditional therapy fails. This article aims to familiarise readers with the evaluation and management of resistant hypertension by outlining the most recent evidence-based treatment options.

  10. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-01-01

    Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

  11. Metabolic syndrome and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Amanda Oliva Gobato

    2014-03-01

    Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  12. Treatment of severe insulin resistance in pregnancy with 500 units per milliliter of concentrated insulin.

    Science.gov (United States)

    Mendez-Figueroa, Hector; Maggio, Lindsay; Dahlke, Joshua D; Daley, Julie; Lopes, Vrishali V; Coustan, Donald R; Rouse, Dwight J

    2013-07-01

    To evaluate glycemic control and pregnancy outcomes among pregnant women with severe insulin resistance treated with 500 units/mL concentrated insulin. Retrospective analysis of gravid women with severe insulin resistance (need for greater than 100 units of insulin per injection or greater than 200 units/d) treated with either 500 units/mL concentrated insulin or conventional insulin therapy. We performed a two-part analysis: 1) between gravid women treated with and without 500 units/mL concentrated insulin; and 2) among gravid women treated with 500 units/mL concentrated insulin, comparing glycemic control before and after its initiation. Seventy-three pregnant women with severe insulin resistance were treated with 500 units/mL concentrated insulin and 78 with conventional insulin regimens. Patients treated with 500 units/mL concentrated insulin were older and more likely to have type 2 diabetes mellitus. Average body mass index was comparable between both groups (38.6 compared with 40.4, P=.11) as were obstetric and perinatal outcomes and glycemic control during the last week of gestation. Within the 500 units/mL concentrated insulin cohort, after initiation of this medication, fasting and postprandial blood glucose concentrations improved. However, the rates of blood glucose values less than 60 mg/dL and less than 50 mg/dL were higher in the 500 units/mL concentrated insulin group after initiation than before, 4.8% compared with 2.0% (Pinsulin in severely obese insulin-resistant pregnant women confers similar glycemic control compared with traditional insulin regimens but may increase the risk of hypoglycemia. II.

  13. Insulin resistance in drug naive patients with multiple sclerosis

    OpenAIRE

    Kostić Smiljana; Kolić Ivana; Raičević Ranko; Stojanović Zvezdana; Kostić Dejan; Dinčić Evica

    2017-01-01

    Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS), the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR) and reduced insulin sensitivity (IS) in untreated patie...

  14. Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

    Science.gov (United States)

    de Campos Mazo, Daniel Ferraz; Mattar, Rejane; Stefano, José Tadeu; da Silva-Etto, Joyce Matie Kinoshita; Diniz, Márcio Augusto; Duarte, Sebastião Mauro Bezerra; Rabelo, Fabíola; Lima, Rodrigo Vieira Costa; de Campos, Priscila Brizolla; Carrilho, Flair José; Oliveira, Claudia P

    2016-01-01

    .651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)]. CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients. PMID:27648154

  15. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

    Directory of Open Access Journals (Sweden)

    April J. Stull

    2016-11-01

    Full Text Available Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM. These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to establish the role of blueberries in preventing or delaying T2DM.

  16. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

    Science.gov (United States)

    Højlund, Kurt

    2014-07-01

    Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

  17. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    Science.gov (United States)

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  18. Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals

    DEFF Research Database (Denmark)

    Roussel, Ronan; Natali, Andrea; Balkau, Beverley

    2016-01-01

    Objective: It is a common belief that early atherosclerosis in prediabetes is causally linked to endothelial insulin resistance. Another condition, a low insulin secretion, may be associated with insufficient insulin action on the vascular wall and consequently favor atherosclerosis. Our aim...... was to test this hypothesis in people without diabetes, taking into account the gold-standard measurement of insulin sensitivity, a major confounder in the relationship between insulin secretion and atherosclerosis. Methods: We studied the European Relationship between Insulin Sensitivity and Cardiovascular...... Risk cohort of 451 men and 593 women (44±8 years, mean±SD) who were free of diabetes, hypertension, dyslipidemia, and other known chronic or acute conditions. All underwent an oral glucose tolerance test, a euglycemic-hyperinsulinemic clamp (M/I measured insulin sensitivity), and B-mode carotid...

  19. Prevalence and characteristics of resistant hypertensive patients in an Asian population

    Directory of Open Access Journals (Sweden)

    Rabia Naseem

    2017-07-01

    Conclusion: Nearly one in ten hypertensive patients had true resistant hypertension, and twenty-five percent of patients had pseudo-resistance. Resistance hypertensions is significantly associated with female gender, older age, obesity, dietary noncompliance and increased use of NSAIDs.

  20. Insulin resistance and atherosclerosis : the role of visceral fat

    NARCIS (Netherlands)

    Gast, K.B.

    2016-01-01

    The main objective of this thesis was to unravel relationships between obesity, insulin resistance, hyperglycemia, and atherosclerosis. It is well-established that patients with type 2 diabetes have a 2- to 3-fold increased risk of cardiovascular disease. We investigated whether insulin resistance

  1. Method for preventing and/or treating insulin resistance

    NARCIS (Netherlands)

    Nieuwdorp, M.; Vos, de W.M.

    2013-01-01

    The present invention describes use of Eubacterium hallii et rel. and/or Alcaligenes faecalis et rel., as well as pharmaceutical, food, or feed compositions comprising these bacteria, as a medicament, in particular for preventing and/or treating insulin resistance and/or insulin resistance-related

  2. Whole-Body and Hepatic Insulin Resistance in Obese Children

    Science.gov (United States)

    Ibarra-Reynoso, Lorena del Rocío; Pisarchyk, Liudmila; Pérez-Luque, Elva Leticia; Garay-Sevilla, Ma. Eugenia; Malacara, Juan Manuel

    2014-01-01

    Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance. PMID:25411786

  3. Relationship between insulin resistance and tissue blood flow in preeclampsia.

    Science.gov (United States)

    Anim-Nyame, Nick; Gamble, John; Sooranna, Suren R; Johnson, Mark R; Steer, Philip J

    2015-05-01

    Preeclampsia is characterized by generalized endothelial dysfunction and impaired maternal tissue perfusion, and insulin resistance is a prominent feature of this disease. The aim of this study was to test the hypothesis that insulin resistance in preeclampsia is related to the reduced resting tissue blood flow. We used venous occlusion plethysmography to compare the resting calf muscle blood flow (measured as QaU) in 20 nulliparous women with preeclampsia and 20 normal pregnant controls matched for maternal age, gestational age, parity and BMI during the third trimester. Fasting blood samples were obtained to measure the plasma concentrations of insulin and glucose, and to calculate the fasting insulin resistance index (FIRI), a measure of insulin resistance in both groups of women. Calf blood flow was significantly reduced in the preeclampsia group (1.93 ± 0.86 QaU), compared with normal pregnant controls (3.94 ± 1.1 QaU, P insulin concentrations and Insulin Resistance Index were significantly higher in preeclampsia compared with normal pregnancy (P insulin concentrations (r = -0.57, P = 0.008) and FIRI (r = -0.59, P = 0.006) in preeclampsia, but not in normal pregnancy. These findings support our hypothesis and raise the possibility that reduced tissue blood flow may a play a role in the increased insulin resistance seen in preeclampsia.

  4. Brain natriuretic peptide and insulin resistance in older adults.

    Science.gov (United States)

    Kim, F; Biggs, M L; Kizer, J R; Brutsaert, E F; de Filippi, C; Newman, A B; Kronmal, R A; Tracy, R P; Gottdiener, J S; Djoussé, L; de Boer, I H; Psaty, B M; Siscovick, D S; Mukamal, K J

    2017-02-01

    Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. © 2016 Diabetes UK.

  5. Familial short fifth metacarpals and insulin resistance

    International Nuclear Information System (INIS)

    Hyari, Muwafag; Hamamy, Hanan; Barham, Muries; Ajlouni, Kamel; Al-Hadidy, Azmy

    2006-01-01

    Very few reports on the phenotype of short fifth metacarpals have been published in the medical literature. We report a Jordanian family in which three sisters aged 15, 13 and 8 years revealed bilateral shortening of the fifth fingers and radiological shortening of the fifth metacarpals. The father had unilateral short fifth metacarpal. The elder two sisters, their father as well as their brother and another sister manifested insulin resistance. Spherocytosis was diagnosed in one of the girls and her father. The parents are non-consanguineous. This constellation of findings has not been previously reported and could point to the presence of two disorders segregating in the family or to a novel syndrome with autosomal dominant inheritance and variable expressivity. (orig.)

  6. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  7. Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study.

    Science.gov (United States)

    Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

    2015-01-01

    Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

  8. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

  9. Insulin Sensitivity Determines Effects of Insulin and Meal Ingestion on Systemic Vascular Resistance in Healthy Subjects.

    Science.gov (United States)

    Woerdeman, Jorn; Meijer, Rick I; Eringa, Etto C; Hoekstra, Trynke; Smulders, Yvo M; Serné, Erik H

    2016-01-01

    In addition to insulin's metabolic actions, insulin can dilate arterioles which increase blood flow to metabolically active tissues. This effect is blunted in insulin-resistant subjects. Insulin's effect on SVR, determined by resistance arterioles, has, however, rarely been examined directly. We determined the effects of both hyperinsulinemia and a mixed meal on SVR and its relationship with insulin sensitivity. Thirty-seven lean and obese women underwent a hyperinsulinemic-euglycemic clamp, and 24 obese volunteers underwent a mixed-meal test. SVR was assessed using CPP before and during hyperinsulinemia as well as before and 60 and 120 minutes after a meal. SVR decreased significantly during hyperinsulinemia (-13%; p Insulin decreased SVR more strongly in insulin-sensitive individuals (standardized β: -0.44; p = 0.01). In addition, SVR at 60 minutes after meal ingestion was inversely related to the Matsuda index (β: -0.39; p = 0.04) and the change in postprandial SVR was directly related to postprandial glycemia (β: 0.53; p insulin resistance. This suggests that resistance to insulin-induced vasodilatation contributes to regulation of vascular resistance. © 2015 John Wiley & Sons Ltd.

  10. Characteristics of Resistant Hypertension in a Large Ethnically Diverse Hypertension Population of an Integrated Health System

    Science.gov (United States)

    Sim, John J.; Bhandari, Simran K.; Shi, Jiaxiao; In Liu, Lu A.; Calhoun, David A.; McGlynn, Elizabeth A.; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.

    2013-01-01

    Objective To evaluate the prevalence and characterize resistant hypertension from a large representative population with successful hypertension management and reliable health information. Patient and Methods We performed a cross sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system during 1/1/2006–12/31/2007. From individuals age >17 years with hypertension, resistant hypertension was identified and prevalence determined. Multivariable logistic regression was used to calculate odds ratios (OR) with adjustments for demographics, clinical variables, and medication use. Results Among 470,386 hypertensive individuals, 12.8% were identified as resistant representing15.3% of those on medications. Overall, 37,061 (7.9%) had uncontrolled hypertension while on ≥ 3 medicines. OR (95% confidence interval) for resistant hypertension were greater for black race (1.68, 1.62–1.75), older age (1.11, 1.10–1.11 for every 5 year increase), males (1.06, 1.03–1.10), and obesity (1.46, 1.42–1.51). Medication adherence rates were higher in resistant hypertension (93 vs 90%, phypertension. Conclusion Within a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable to past studies using more fragmented data sources. Past observations have been limited due to non-representative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort which was established with an electronic medical record based approach has the potential to provide a better understanding of resistant hypertension and outcomes. PMID:24079679

  11. Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Bolinder, J.; Ostman, J.; Arner, P.

    1982-01-01

    The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

  12. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.

    Science.gov (United States)

    Pedrosa, Rodrigo P; Drager, Luciano F; Gonzaga, Carolina C; Sousa, Marcio G; de Paula, Lílian K G; Amaro, Aline C S; Amodeo, Celso; Bortolotto, Luiz A; Krieger, Eduardo M; Bradley, T Douglas; Lorenzi-Filho, Geraldo

    2011-11-01

    Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9-14.2]; Phypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

  13. Insulin resistance and mitochondrial function in skeletal muscle

    DEFF Research Database (Denmark)

    Dela, Flemming; Helge, Jørn Wulff

    2013-01-01

    are used in the attempt to resolve the mechanisms of insulin resistance. In this context, a dysfunction of mitochondria in the skeletal muscle has been suggested to play a pivotal role. It has been postulated that a decrease in the content of mitochondria in the skeletal muscle can explain the insulin...... resistance. Complementary to this also specific defects of components in the respiratory chain in the mitochondria have been suggested to play a role in insulin resistance. A key element in these mechanistic suggestions is inability to handle substrate fluxes and subsequently an accumulation of ectopic...... intramyocellular lipids, interfering with insulin signaling. In this review we will present the prevailing view-points and argue for the unlikelihood of this scenario being instrumental in human insulin resistance. This article is part of a Directed Issue entitled: Bioenergetic dysfunction....

  14. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

    DEFF Research Database (Denmark)

    Ruzzin, Jérôme; Petersen, Rasmus; Meugnier, Emmanuelle

    2010-01-01

    BACKGROUND: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens...... of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking. OBJECTIVE: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders. METHODS: Wistar rats were exposed...... salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, gene expression and performed microarray analysis. RESULTS: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity...

  15. Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

    Science.gov (United States)

    Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

    2013-01-01

    The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively. Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, Pinsulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM. Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

  16. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes.

    Science.gov (United States)

    Patel, Tushar P; Rawal, Komal; Bagchi, Ashim K; Akolkar, Gauri; Bernardes, Nathalia; Dias, Danielle da Silva; Gupta, Sarita; Singal, Pawan K

    2016-01-01

    Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-β, IRS-1, PI3K, Akt, Glut4 and PGC-1α that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here.

  17. Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

    Science.gov (United States)

    Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

    2010-01-01

    The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic

  18. Polycystic ovary syndrome (PCOS), insulin resistance and insulin-like growth factors (IGfs)/IGF-binding proteins (IGFBPs).

    Science.gov (United States)

    Wang, Hsin-Shih; Wang, Tzu-Hao

    2003-08-01

    Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmatic generation of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. A growing body of evidence suggests that PCOS patients with hyperinsulinemia have a higher risk to develop diabetes mellitus, hypertension and cardiovascular disease as compared to age-matched women. Although oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies, weight loss should also be vigorously encouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies to alleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.

  19. Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

    Science.gov (United States)

    Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

    2013-05-01

    The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

  20. Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

    Science.gov (United States)

    Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

    2018-06-01

    Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

  2. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    International Nuclear Information System (INIS)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

    2015-01-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  3. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  4. Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro

    Directory of Open Access Journals (Sweden)

    Ying Xu

    2016-04-01

    Full Text Available It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN. Here we used shRNA transfection to knockdown the insulin receptor (IR gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation. The present study deepens our understanding of the role of autophagy in the pathogenesis of DN.

  5. Related Factors of Insulin Resistance in Korean Children: Adiposity and Maternal Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Kang-Sook Lee

    2011-12-01

    Full Text Available Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model assessment of insulin resistance (HOMA-IR was calculated using fasting glucose and insulin level as a marker of IR. All children’s adiposity indices (r = 0.309–0.318, all P-value = 0.001 and maternal levels of fasting insulin (r = 0.285, P-value = 0.003 and HOMA-IR (r = 0.290, P-value = 0.002 were positively correlated with children’s HOMA-IR level. There was no statistical difference of children’s HOMA-IR level according to children’s lifestyle habits and socioeconomic status of families. An increase of 1 percentage point in body fat was related to 2.7% increase in children’s HOMA-IR (P-value < 0.001 and an increase of 1% of maternal level of HOMA-IR was related to 0.2% increase in children’s HOMA-IR (P-value = 0.002. This study shows that children’s adiposity and maternal IR are positively associated with children’s IR.

  6. [Insulin resistance in the pathogenesis of polycystic ovarian disease (PCOD)].

    Science.gov (United States)

    Jakowicki, J

    1994-10-01

    In polycystic ovarian disease there is a strong association between hyperinsulinemia and hyperandrogenism but not with obesity alone. The magnitude of peripheral insulin resistance is similar to that seen in non-insulin-dependent diabetes mellitus. Mild hyperinsulinemia in PCOD patients is not impair the carbohydrate metabolism. The elimination of the cause of hyperandrogenism by bilateral oophorectomy, long-acting Gn-RH agonist or antiandrogen cyproterone acetate did not improve the associated insulin resistance. In opposition to insulin resistance in the tissues responsible for metabolism of carbohydrate, the ovary remains sensitive to the effects of pancreatic hormone. Presumably this mechanism involved the interaction with IGF-I receptors to stimulate thecal and stromal androgen production. Insulin may sensitize the stroma to the stimulatory effect of LH. In the mechanism of follicular arrest take part increased level of binding proteins for IGF-I, mainly IGFBP 2, -4 and 5 inhibit FSH and IGF-I action.

  7. Skeletal muscle inflammation and insulin resistance in obesity

    Science.gov (United States)

    Wu, Huaizhu; Ballantyne, Christie M.

    2017-01-01

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

  8. The Association Between IGF-I and Insulin Resistance

    DEFF Research Database (Denmark)

    Friedrich, Nele; Thuesen, Betina; Jørgensen, Torben

    2012-01-01

    OBJECTIVEIGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate...... the association between IGF-I level and insulin resistance in a Danish general population.RESEARCH DESIGN AND METHODSIncluded were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin...... with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.CONCLUSIONSLow- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism...

  9. Current concepts in the management of resistant hypertension: a ...

    African Journals Online (AJOL)

    Background: Resistant hypertension is defined as uncontrolled hypertension above the target goal despite treatment with 3 or more antihypertensive agents, one of which is a diuretic, at optimum and best tolerated doses. The target blood pressure is defined as < 140/90 mmHg in most people and < 130/80 mmHg in those ...

  10. Apo E isoforms, insulin output and plasma lipid levels in essential hypertension.

    Science.gov (United States)

    Dembińska-Kieć, A; Kawecka-Jaszcz, K; Kwaśniak, M; Guevara, I; Pankiewicz, J; Malczewska-Malec, M; Iwanejko, J; Hartwich, J; Zdzienicka, A; Stochmal, A; Leszczyńska-Gołabek, I

    1998-02-01

    The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.

  11. [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

    Science.gov (United States)

    Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

    2015-01-01

    Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  12. Hypertension in the course of insulin dependent diabetes mellitus and its pathogenetic mechanisms

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Nørgaard, K; Jensen, T

    1990-01-01

    All IDDM patients without late complications have blood pressures similar to the nondiabetic background population, and those who develop clinical nephropathy in Denmark have no familial predisposition to hypertension. Blood pressure remains normal until after development of microalbuminuria......, indicating no primary role for hypertension in the pathogenesis of nephropathy. When microalbuminuria is present it does, however, play a crucial role in the progression of nephropathy. Sodium retention, possibly induced by hyperinsulinemia, and perhaps glucose-coupled sodium reabsorption in insulin treated...

  13. [Spironolactone in patients with resistant hypertension].

    Science.gov (United States)

    Rodilla, Enrique; Costa, José A; Pérez-Lahiguera, Francisco; González, Carmen; Pascual, José M

    2008-10-04

    The aim of the study was to assess the effect of adding spironolactone to hypertensive resistant (HTR) patients and characterize those who respond effectively. Observational retrospective study on outpatients with HTR (being treated with at least 3 drugs at full doses, one of these being a diuretic) not achieving blood pressure (BP) goals, with normal creatinine values (< 1.6 mg/dl for males and < 1.4 mg/dl in women). A total of 95 patients (70% male), average (standard deviation) age of 66 (12) years (40% diabetics), were treated with spironolactone during 4 months (range: 2-13). Mean systolic and diastolic BP fell from 170/86 (20/14) mmHg, by 29/12 mmHg (95% confidence interval [CI], 25 to 33/10 to 14 mmHg; p = 0.001). At the end of follow-up, 38% of all patients achieved the goal of BP control. Initial systolic BP < 165 mmHg (odds ratio [OR] = 3,97; 95% CI, 1.52-10.37; p = 0.005), and diabetes (OR = 0.33; 95% CI, 0.13-0.86; p = 0.02) were the only independent factors related to BP control in a logistic regression analysis. The addition of spironolactone effectively lowers BP in patients with HTR treated with 3 drugs. BP control is more difficult to achieve in diabetics.

  14. Radiation resistivity of frozen insulin solutions and suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Soboleva, N N; Ivanova, A I; Talrose, V L; Trofimov, V I; Fedotov, V P [AN SSSR, Moscow. Inst. Fizicheskoj Khimii; Research Institute for Biological Testing of Chemicals, Moscow (USSR); Institute of Experimental Endocrinology and Hormon Chemistry, Moscow (USSR))

    1981-10-01

    The effect of great increase in radiation resistance of insulin solutions and suspensions after irradiation at low temperatures in the frozen state was observed by absorption spectrophotometry, paper chromatography and biological analysis. The data obtained suggest irradiation of frozen insulin solutions and suspensions as a method for its sterilization.

  15. Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

    Science.gov (United States)

    Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

    2016-03-01

    Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important

  16. Gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes

    International Nuclear Information System (INIS)

    Ahmed, S.; Ahmad, A.

    2010-01-01

    To determine the relationship of insulin resistance with microalbuminuria in patients of type-2 Diabetes mellitus and observe gender difference if any. Study Design: A cross-sectional study. Place and Duration of Study: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to August 2007. Methodology: One hundred and fifty five patients of type-2 Diabetes mellitus were included in the study who had either microalbuminuria or normo albuminuria. Body mass index, waist circumference and blood pressure were recorded. Fasting venous blood sample was collected for plasma glucose (FPG), serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c. Urine albumin excretion was determined using urine albumin to creatinine ratio. Insulin resistance was calculated from fasting plasma glucose and serum insulin levels, using homeostatic model assessment of insulin resistance (HOMA-IR). Correlation and association testing was carried out with significance at p < 0.05. Results: Microalbuminuria was found to be significantly correlated with HOMA-IR (r = 0.33, p < 0.001), serum insulin (r = 0.28, p = < 0.001), body mass index (r = 0.18, p = 0.02) and waist circumference (r = 0.21, p = 0.008). This correlation was more significant in women (n = 85, r = 0.48, p = < 0.0001) as compared to men (n = 70, r = 0.14, p = 0.12). The correlation between HOMA-IR and urine albumin excretion remained highly significant (p = 0.001) after controlling for gender, age, duration of diabetes, waist circumference, hypertension, triglycerides and HbA1c. Conclusion: Urinary albumin excretion in patients of type-2 diabetes is strongly associated with insulin resistance and related cardiovascular risk factors. This association appears to be stronger in women than the men, in our population. (author)

  17. Xylitol prevents NEFA-induced insulin resistance in rats

    Science.gov (United States)

    Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

    2013-01-01

    Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

  18. The etiology of oxidative stress in insulin resistance

    Directory of Open Access Journals (Sweden)

    Samantha Hurrle

    2017-10-01

    Full Text Available Insulin resistance is a prevalent syndrome in developed as well as developing countries. It is the predisposing factor for type 2 diabetes mellitus, the most common end stage development of metabolic syndrome in the United States. Previously, studies investigating type 2 diabetes have focused on beta cell dysfunction in the pancreas and insulin resistance, and developing ways to correct these dysfunctions. However, in recent years, there has been a profound interest in the role that oxidative stress in the peripheral tissues plays to induce insulin resistance. The objective of this review is to focus on the mechanism of oxidative species generation and its direct correlation to insulin resistance, to discuss the role of obesity in the pathophysiology of this phenomenon, and to explore the potential of antioxidants as treatments for metabolic dysfunction.

  19. Diagnostic criteria for sarcopenia relate differently to insulin resistance

    NARCIS (Netherlands)

    Bijlsma, A.Y.; Meskers, C.G.M.; van Heemst, D.; Westendorp, R.G.J.; Craen, A.J.M.; Maier, A.B.

    2013-01-01

    Skeletal muscle is important in insulinstimulated glucose uptake. Sarcopenia is, therefore, a possible risk factor for insulin resistance. Currently, different diagnostic criteria for sarcopenia include low muscle mass, muscle strength, and walking speed. We assessed these muscle characteristics in

  20. Exploring pathway interactions in insulin resistant mouse liver

    NARCIS (Netherlands)

    Kelder, T.; Eijssen, L.; Kleemann, R.; Erk, M. van; Kooistra, T.; Evelo, C.

    2011-01-01

    Background: Complex phenotypes such as insulin resistance involve different biological pathways that may interact and influence each other. Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset.Results: We

  1. Effect of Omega-3 Fatty Acids Treatment on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Mogoş Tiberius

    2014-12-01

    Full Text Available Background and aims: Insulin resistance (IR is a common pathogenic factor of several diseases: diabetes mellitus, the metabolic syndrome, arterial hypertension, atherosclerosis, dyslipidemia, etc. There are many therapeutic factors involved in decreasing IR. Among them we mention metformin, pioglitazone, physical activity, weight loss, diet, etc. In the last decade, there are more observations of the influence of polyunsaturated fatty acids on IR. The most powerful seem to be omega-3 fatty acids. In our study, we wanted to asses if the administration of omega-3 fatty acids is involved in modifying IR. Materials and methods: We evaluated 126 diabetic patients with IR from January 2011 until July 2014. The study was open-label and non-randomized. For the determination of IR we used the HOMA-IR method. Results: For both males and females there was a regression of HOMA-IR during the 4 weeks of treatment with omega-3 and also after 2 weeks after stopping the administration of these fatty acids. The decrease of HOMA-IR was statistically significant (p<0.05. The statistic result observed in the next 2 weeks after stopping administration of omega-3 was also significant (p<0.05.

  2. Insulin resistance and exercise tolerance in heart failure patients

    DEFF Research Database (Denmark)

    Snoer, Martin; Monk-Hansen, Tea; Olsen, Rasmus Huan

    2012-01-01

    Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.......Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage....

  3. RELATIONSHIP BETWEEN URIC ACID METABOLISM AND INSULIN RESISTANCE

    OpenAIRE

    辻本, 伸宏; 金内, 雅夫; 尾崎, 博基; 藤田, 泰三; 中嶋, 民夫; 土肥, 和紘

    1998-01-01

    To investigate the relationship between uric acid (UA) metabolism and insulin resistance, serum creatinine concentration (Scr), serum UA concentration (SuA) and the urinary excretion of creatinine and UA were determined in 25 non-diabetic patients. Creatinine clearance (Ccr) and UA clearance/creatinine clearance ratio (CuA/Ccr) were also calculated. Insulin resistance was evaluated by the euglycemic glucose clamp tech- nique and expressed as the mean value of the glucose infusion rate (M-valu...

  4. Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

    Science.gov (United States)

    Stabile, Gaspare; Borrielli, Irene; Artenisio, Alfredo Carducci; Bruno, Lucia Maria; Benvenga, Salvatore; Giunta, Loretta; La Marca, Antonio; Volpe, Annibale; Pizzo, Alfonsa

    2014-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17β-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  5. Prevalence and determinants of resistant hypertension among ...

    African Journals Online (AJOL)

    ISSN: 1596-5996 (print); 1596-9827 (electronic) ... among hypertensive patients attending a cardiology clinic in China: a ... leading cause of cardiovascular diseases (CVD) ... Hypertension in present study was defined as ... patients who were currently smoking at least one .... prevalence of RHT by Ma et al [19] than us might.

  6. Insulin Resistance Induced by Hyperinsulinemia Coincides with a Persistent Alteration at the Insulin Receptor Tyrosine Kinase Domain

    Science.gov (United States)

    Catalano, Karyn J.; Maddux, Betty A.; Szary, Jaroslaw; Youngren, Jack F.; Goldfine, Ira D.; Schaufele, Fred

    2014-01-01

    Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR) activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK) domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered ‘insulin refractory’ IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated) levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based ‘memory’ of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states. PMID:25259572

  7. Insulin resistance induced by hyperinsulinemia coincides with a persistent alteration at the insulin receptor tyrosine kinase domain.

    Directory of Open Access Journals (Sweden)

    Karyn J Catalano

    Full Text Available Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered 'insulin refractory' IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based 'memory' of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states.

  8. Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

    Directory of Open Access Journals (Sweden)

    Xin-Yu Huang

    2016-01-01

    Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

  9. Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

    Science.gov (United States)

    Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

    2013-08-01

    "Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

  10. Prevalence of hypertension in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Nørgaard, K; Feldt-Rasmussen, B; Borch-Johnsen, K

    1990-01-01

    The prevalence of hypertension in a representative sample (n = 10202) of the Danish general population aged 16-59 years was assessed to 4.4% based on three blood pressure readings. In Type 1 (insulin-dependent) diabetic patients of similar age (n = 1703) the prevalence was determined in a similar...... way to 14.7% (p less than 0.00001). The excess prevalence in Type 1 diabetic patients was due to hypertension in patients with incipient and clinical nephropathy as the prevalence of hypertension among diabetic patients with normal urinary albumin excretion (essential hypertension) was 3.9%, similar...... to that observed in the general population. The patients with Type 1 diabetes and essential hypertension had higher systolic (146 +/- 19 vs 133 +/- 18 mm Hg, p less than 0.00001) and diastolic blood pressure (87 +/- 12 vs 79 +/- 7 mm Hg, p less than 0.00001), but less changes in the eye background than patients...

  11. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  12. Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

    Directory of Open Access Journals (Sweden)

    Qiuwei Wang

    Full Text Available OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function were calculated in maternal and cord blood respectively. RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively. Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019, in the pregnant women with GDM. CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

  13. Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

    Science.gov (United States)

    Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

    2014-08-01

    Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

  14. The gut microbiota, obesity and insulin resistance.

    Science.gov (United States)

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  15. Effect of cigarette smoking on insulin resistance risk.

    Science.gov (United States)

    Haj Mouhamed, D; Ezzaher, A; Neffati, F; Douki, W; Gaha, L; Najjar, M F

    2016-02-01

    Smoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics. This study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6±16.0 and 38.5±21.9 years. All subjects are not diabetic. Fasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR=[fasting insulin (mU/L)×fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance. Compared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine. Our results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers. Copyright © 2015. Published by Elsevier SAS.

  16. Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

    Science.gov (United States)

    Guo, Shaodong

    2014-01-01

    Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies demonstrate that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. PMID:24281010

  17. Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

    OpenAIRE

    Hutchison, Samantha K.; Harrison, Cheryce; Stepto, Nigel; Meyer, Caroline; Teede, Helena J.

    2008-01-01

    OBJECTIVE?Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating ...

  18. Role of nutrition in preventing insulin resistance in children.

    Science.gov (United States)

    Blasetti, Annalisa; Franchini, Simone; Comegna, Laura; Prezioso, Giovanni; Chiarelli, Francesco

    2016-03-01

    Nutrition during prenatal, early postnatal and pubertal period is crucial for the development of insulin resistance and its consequences. During prenatal period fetal environment and nutrition seems to interfere with metabolism programming later in life. The type of dietary carbohydrates, glycemic index, protein, fat and micronutrient content in maternal nutrition could influence insulin sensitivity in the newborn. The effects of lactation on metabolism and nutritional behavior later in life have been studied. Dietary habits and quality of diet during puberty could prevent the onset of a pathological insulin resistance through an adequate distribution of macro- and micronutrients, a diet rich in fibers and vegetables and poor in saturated fats, proteins and sugars. We want to overview the latest evidences on the risk of insulin resistance later in life due to both nutritional behaviors and components during the aforementioned periods of life, following a chronological outline from fetal development to adolescence.

  19. Whole-blood viscosity and the insulin-resistance syndrome.

    Science.gov (United States)

    Høieggen, A; Fossum, E; Moan, A; Enger, E; Kjeldsen, S E

    1998-02-01

    In a previous study we found that elevated blood viscosity was linked to the insulin resistance syndrome, and we proposed that high blood viscosity may increase insulin resistance. That study was based on calculated viscosity. To determine whether directly measured whole-blood viscosity was related to the insulin-resistance syndrome in the same way as calculated viscosity had been found to be. Healthy young men were examined with the hyperinsulinemic isoglycemic glucose clamp technique, and we related insulin sensitivity (glucose disposal rate) to other metabolic parameters and to blood viscosity. We established a technique for direct measurement of whole-blood viscosity. There were statistically significant negative correlations between glucose disposal rate and whole-blood viscosity at low and high shear rates (r = -0.41, P = 0.007 for both, n = 42). Whole-blood viscosity was correlated positively (n = 15) to serum triglyceride (r = 0.54, P = 0.04) and total cholesterol (r = 0.52, P = 0.05), and negatively with high-density lipoprotein cholesterol (r = -0.53, P = 0.04) concentrations. Insulin sensitivity index was correlated positively to high-density lipoprotein cholesterol (r = 0.54, P = 0.04) and negatively to serum triglyceride (r = -0.69, P = 0.005) and to total cholesterol (r = -0.81, P = 0.0003) concentrations. The present results demonstrate for the first time that there is a negative relationship between directly measured whole-blood viscosity and insulin sensitivity as a part of the insulin-resistance syndrome. Whole-blood viscosity contributes to the total peripheral resistance, and these results support the hypothesis that insulin resistance has a hemodynamic basis.

  20. 92 INSULIN RESISTANCE: CAUSES AND METABOLIC ...

    African Journals Online (AJOL)

    drclement

    2009-12-01

    Dec 1, 2009 ... Edo State Institute of Technology and Management. Usen, Edo State ... type 2 diabetes mellitus. The cause of the vast ... Insulin (molecular mass 6000D) consists of 51 amino acids .... Experimental Biology and. Medicine 2004 ...

  1. Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine.

    Science.gov (United States)

    Belwal, Tarun; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Habtemariam, Solomon

    2017-10-12

    Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic β-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent hyperglycemia (diabetes), hyperinsulinemia, fatty acids and/or lipid dysregulation which are often prevalent under obesity conditions. Hence, insulin sensitizers are one class of drugs currently employed to treat diabetes and associated metabolic disorders. A number of natural products that act through multiple mechanisms have also been identified to enhance insulin sensitivity in target organs. One group of such compounds that gained interest in recent years are the dietary anthocyanins. Data from their in vitro, in vivo and clinical studies are scrutinized in this communication to show their potential health benefit through ameliorating insulin resistance. Specific mechanism of action ranging from targeting specific signal transduction receptors/enzymes to the general antioxidant and anti-inflammatory mechanisms of insulin resistance are presented.

  2. Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

    Science.gov (United States)

    Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H; Johnson, Antoinette; Shehata, Hassan

    2017-12-01

    To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation ( p  = 0.514) or at 28 weeks ( p  = 0.643). Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

  3. Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension.

    Science.gov (United States)

    Sung, Ki-Chul; Park, Hyun-Young; Kim, Min-Ju; Reaven, Gerald

    2016-03-22

    Questions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension. Analysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, ≥40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio). Fully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02-2.20, P = 0.25) and 2.02 (1.35-3.02, P insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension.

  4. Association between omentin levels and insulin resistance in pregnancy.

    Science.gov (United States)

    Aktas, G; Alcelik, A; Ozlu, T; Tosun, M; Tekce, B K; Savli, H; Tekce, H; Dikbas, O

    2014-03-01

    Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, non-diabetic women. Uncomplicated pregnant women who admit to our outpatient clinics for routine follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  5. Association of insulin resistance with obesity in children

    International Nuclear Information System (INIS)

    Siddiqui, S.A.; Bashir, S.; Shabbir, I.; Sherwani, M.K.; Aasim, M.

    2011-01-01

    Background: Insulin resistance is the primary metabolic disorder associated with obesity. Little is known about its role as a determinant of the metabolic syndrome in obese children. Objectives: To assess the association of insulin resistance with metabolic syndrome in obese and non obese children. Study type and settings: Cross sectional analytical study conducted among children of ten Municipal Corporation high schools of Data Ganj Buksh Town Lahore. Subjects and Methods: A total of 46 obese and 49 non obese children with consent were recruited for the study. Fasting blood glucose, serum insulin, high density lipoprotein in cholesterol, triglycerides, cholesterol, non HDL-cholesterol LDL-cholesterol were measured using standard methods. Data were analyzed by using statistical software SPSS-Version 15. Results: A total of 95 children 49 obese and 46 non obese were recruited for the study. A significant association of serum triglyceride(p<0.001), high density lipoprotein cholesterol(p<0.001), fasting blood glucose(p<0.001), and insulin levels (p<0.001) , was seen between the two groups. For each component of metabolic syndrome, when insulin resistance increased so did odds ratios for cardio metabolic risk factors. Conclusions: Insulin resistance was seen in 34.7% children. Metabolic syndrome was found in 31.6% children reflecting that obese children are at high risk for metabolic syndrome and have low HDL-cholesterol and high triglycerides levels. (author)

  6. An approach to diagnosis and management of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Hitesh C Patel

    2015-01-01

    Full Text Available Hypertension is a key determinant of cardiovascular disease morbidity and mortality, directly accounting for approximately 10% of deaths in India. There is a causal association between the magnitude of blood pressure (BP elevation and adverse cardiovascular event rate, which provides the rationale for implementing BP reduction in routine clinical practice. However, an estimated 30-50% of the hypertensive population remain uncontrolled with a BP >140/90 mmHg, of whom a subgroup fulfill the diagnostic criteria for resistant hypertension. This cohort lies at the extreme end of the cardiovascular risk spectrum, and hence stands to benefit most from specialist input to optimize BP control. This review summarizes a management approach in patients with resistant hypertension, focusing on accurate diagnosis and evidence-based treatments.

  7. Homeostatic model assessment for insulin resistance (homa-ir): a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    Majid, H.; Khan, A.H.; Masood, Q.

    2017-01-01

    To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). Study Design: Observational study. Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. Methodology: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value =12 micro IU/ml. Results: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 +-5.5 years. Mean HOMA-IR of women was 3.1 +-1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 +-5.8 micro IU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. Conclusion: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMA-IR model performed better than hyperinsulinemia alone for diagnosing IR. (author)

  8. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Majid, Hafsa; Masood, Qamar; Khan, Aysha Habib

    2017-03-01

    To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). Observational study. Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value HOMA-IR of women was 3.1 ±1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 ±5.8 µIU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR.

  9. Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes

    DEFF Research Database (Denmark)

    Holmes-Truscott, Elizabeth; Skinner, Timothy Chas; Pouwer, F

    2016-01-01

    to the model. CONCLUSIONS: Psychological insulin resistance may reflect broader distress about diabetes and concerns about its treatment but not general beliefs about medicines, depression or anxiety. Reducing diabetes distress and current treatment concerns may improve attitudes towards insulin as a potential......AIMS: To investigate the contribution of general and diabetes-specific emotional wellbeing and beliefs about medicines in the prediction of insulin therapy appraisals in adults with non-insulin-treated type 2 diabetes. METHODS: The sample included Diabetes MILES-Australia cross-sectional survey...... diabetes medications (BMQ Specific); negative insulin therapy appraisals (ITAS); depression (PHQ-9); anxiety (GAD-7), and diabetes distress (DDS-17). Factors associated with ITAS Negative scores were examined using hierarchical multiple regressions. RESULTS: Twenty-two percent of the variance in ITAS...

  10. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

    DEFF Research Database (Denmark)

    de Rooij, Susanne R; Dekker, Jacqueline M; Kozakova, Michaela

    2009-01-01

    OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...... of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds...... ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin...

  11. Peripheral insulin resistance and impaired insulin signaling contribute to abnormal glucose metabolism in preterm baboons.

    Science.gov (United States)

    Blanco, Cynthia L; McGill-Vargas, Lisa L; Gastaldelli, Amalia; Seidner, Steven R; McCurnin, Donald C; Leland, Michelle M; Anzueto, Diana G; Johnson, Marney C; Liang, Hanyu; DeFronzo, Ralph A; Musi, Nicolas

    2015-03-01

    Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors.

  12. Unilateral Carotid Body Resection in Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Krzysztof Narkiewicz, MD

    2016-08-01

    Full Text Available Animal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension.

  13. Intramuscular Lipid Metabolism in the Insulin Resistance of Smoking

    OpenAIRE

    Bergman, Bryan C.; Perreault, Leigh; Hunerdosse, Devon M.; Koehler, Mary C.; Samek, Ali M.; Eckel, Robert H.

    2009-01-01

    OBJECTIVE Smoking decreases insulin action and increases the risk of type 2 diabetes in humans. Mechanisms responsible for smoking-induced insulin resistance are unclear. We hypothesized smokers would have increased intramuscular triglyceride (IMTG) and diacylglycerol (DAG) concentration and decreased fractional synthesis rate (FSR) compared with nonsmokers. RESEARCH DESIGN AND METHODS Nonsmokers (n = 18, aged 20 ± 0.5 years, BMI 22 ± 0.4 kg/m2, body fat 20 ± 2%, 0 cigarettes per day) and smo...

  14. Renal denervation in moderate treatment-resistant hypertension.

    Science.gov (United States)

    Ott, Christian; Mahfoud, Felix; Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A; Veelken, Roland; Spies, Aline; Ukena, Christian; Laufs, Ulrich; Uder, Michael; Böhm, Michael; Schmieder, Roland E

    2013-11-12

    This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

    International Nuclear Information System (INIS)

    Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

    2006-01-01

    Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

  16. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Science.gov (United States)

    Matioli, Maria Niures P.S.; Nitrini, Ricardo

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

  17. Midkine, a potential link between obesity and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Nengguang Fan

    Full Text Available Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance. Midkine (MK is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance. It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-α and rosiglitazone. In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4 to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3 pathway in adipocytes. Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.

  18. Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance.

    Science.gov (United States)

    Arai, Chikako; Arai, Norie; Mizote, Akiko; Kohno, Keizo; Iwaki, Kanso; Hanaya, Toshiharu; Arai, Shigeyuki; Ushio, Simpei; Fukuda, Shigeharu

    2010-12-01

    Trehalose has been shown to evoke lower insulin secretion than glucose in oral saccharide tolerance tests in humans. Given this hypoinsulinemic effect of trehalose, we hypothesized that trehalose suppresses adipocyte hypertrophy by reducing storage of triglyceride and mitigates insulin resistance in mice fed a high-fat diet (HFD). Mice were fed an HFD and given drinking water containing 2.5% saccharide (glucose [Glc], trehalose [Tre], maltose [Mal], high-fructose corn syrup, or fructose [Fru]) ad libitum. After 7 weeks of HFD and saccharide intake, fasting serum insulin levels in the Tre/HFD group were significantly lower than in the Mal/HFD and Glc/HFD groups (P fructose corn syrup/HFD, or Fru/HFD group. Analysis of gene expression in mesenteric adipocytes showed that no statistically significant difference in the expression of monocyte chemoattractant protein-1 (MCP-1) messenger RNA (mRNA) was observed between the Tre/HFD group and the distilled water/standard diet group, whereas a significant increase in the MCP-1 mRNA expression was observed in the Glc/HFD, Mal/HFD, Fru/HFD, and distilled water/HFD groups. Thus, our data indicate that trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in HFD-fed mice by reducing insulin secretion and down-regulating mRNA expression of MCP-1. These findings further suggest that trehalose is a functional saccharide that mitigates insulin resistance. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Assesment of propolis supplementation on insulin resistance in diabetic patients

    Directory of Open Access Journals (Sweden)

    nazli samadi

    2017-05-01

    Full Text Available Introduction: Diabetes mellitus is a common endocrine disease . The number of people with diabetes over the last twenty years has doubled . Asia as a result of rapid economic growth , as the center of the epidemic in the world . Iran is among the countries with a high prevalence of diabetes mellitus . Use of medicinal plants as adjunctive therapy along with medication always been original . In recent years the tendency of patients to alternative therapies and traditional medicine has increased. Methods : Among patients referred to clinics of University of Medical Sciences, Yazd, Iran , 67 people were selected and randomly divided into two groups,intervention or placebo. Patients in the intervention group received 3 tablets of 300 mg bee propolis and in the control group received placebo . The study lasted 12 weeks . Serum insulin and insulin resistance index were evaluated at the beginning and end of the study. Results: 57 patients completed the study . The average demographic characteristics , anthropometric indices , serum insulin and insulin resistance index at the beginning and end of the study between the two groups showed no significant difference. Conclusion : In this study , supplementation with bee propolis for 12 weeks , on the serum insulin and indices of insulin resistance in patients with type II diabetes is not effective . Further studies are needed to make a final decision.

  20. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Maria Niures P.S. Matioli

    Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

  1. Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats

    International Nuclear Information System (INIS)

    Cecchin, F.; Ittoop, O.; Sinha, M.K.; Caro, J.F.

    1988-01-01

    The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125 I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the β-subunit and insulin receptor kinase activity using Glu 80 , Tyr 20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled α-subunit and the phosphorylated β-subunit, were normal in uremia. 125 I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase

  2. Sex differences in insulin resistance in GABAB1 knockout mice.

    Science.gov (United States)

    Bonaventura, M M; Rodriguez, D; Ferreira, M L; Crivello, M; Repetto, E M; Bettler, B; Libertun, C; Lux-Lantos, V A

    2013-02-27

    We have previously demonstrated that the absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor β subunit (IRβ), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRβ, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle.

    Science.gov (United States)

    Henriksen, Erik J; Prasannarong, Mujalin

    2013-09-25

    The canonical renin-angiotensin system (RAS) involves the initial action of renin to cleave angiotensinogen to angiotensin I (ANG I), which is then converted to ANG II by the angiotensin converting enzyme (ACE). ANG II plays a critical role in numerous physiological functions, and RAS overactivity underlies many conditions of cardiovascular dysregulation. In addition, ANG II, by acting on both endothelial and myocellular AT1 receptors, can induce insulin resistance by increasing cellular oxidative stress, leading to impaired insulin signaling and insulin-stimulated glucose transport activity. This insulin resistance associated with RAS overactivity, when coupled with progressive ß-cell dysfunction, eventually leads to the development of type 2 diabetes. Interventions that target RAS overactivity, including ACE inhibitors, ANG II receptor blockers, and, most recently, renin inhibitors, are effective both in reducing hypertension and in improving whole-body and skeletal muscle insulin action, due at least in part to enhanced Akt-dependent insulin signaling and insulin-dependent glucose transport activity. ANG-(1-7), which is produced from ANG II by the action of ACE2 and acts via Mas receptors, can counterbalance the deleterious actions of the ACE/ANG II/AT1 receptor axis on the insulin-dependent glucose transport system in skeletal muscle. This beneficial effect of the ACE2/ANG-(1-7)/Mas receptor axis appears to depend on the activation of Akt. Collectively, these findings underscore the importance of RAS overactivity in the multifactorial etiology of insulin resistance in skeletal muscle, and provide support for interventions that target the RAS to ameliorate both cardiovascular dysfunctions and insulin resistance in skeletal muscle tissue. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Acanthosis nigricans: a flag for insulin resistance

    African Journals Online (AJOL)

    2013-11-04

    Nov 4, 2013 ... Outcome measures: OGTT, fasting serum insulin and HOMA IR were the outcome measures studied. Results: This cross-sectional study revealed that 94 subjects with acanthosis nigricans (31.34%) had IR. Grades III and IV, and textures II and III, were more predictive of IR. Acanthosis nigricans grading was ...

  5. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  6. Acute pain induces insulin resistance in humans

    DEFF Research Database (Denmark)

    Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn

    2001-01-01

    Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

  7. hypertension

    Directory of Open Access Journals (Sweden)

    Emine Hatipoglu

    2013-05-01

    Full Text Available Hypertension is a common disease associated with important cardiovascular complications. Persistent blood pressure of 140/90 or higher despite combined use of a reninangiotensin system blocker, calcium channel blocker and a diuretic at highest tolerated doses constitutes resistant hypertension. Excess sympathetic activity plays an important pathogenic role in resistant hypertension in addition to contributing to the development of metabolic problems, in particular diabetes. Reduction of renal sympathetic activity by percutaneous catheter-based radiofrequency ablation via the renal arteries has been shown in several studies to decrease blood pressure in patients with resistant hypertension, and importantly is largely free of significant complications. However, longer term follow-up is required to confirm both long-term safety and efficacy.

  8. Diagnosis and management of resistant hypertension: state of the art.

    Science.gov (United States)

    Wei, Fang-Fei; Zhang, Zhen-Yu; Huang, Qi-Fang; Staessen, Jan A

    2018-04-26

    Resistant hypertension is defined as a lack of ambulatory blood pressure response to optimized medical treatment after exclusion of secondary hypertension in patients who are fully adherent to antihypertensive therapy. Patients with resistant hypertension are at high risk of complications, particularly cardiovascular events, and optimization of medical treatment remains the cornerstone of their management. Such optimization should be based on simple algorithms and include the use of aldosterone antagonists. The available data from clinical trials do not support the use of device-based approaches such as renal denervation, baroreflex activation therapy or arteriovenous anastomosis for the treatment of resistant hypertension in the majority of patients. Therefore, device treatment remains a last-resort for patients with truly resistant hypertension in the context of clinical research in highly skilled tertiary referral centres. Future research should focus on improving understanding of the intrinsic (physiological and psychological factors) and extrinsic (environmental stressors) mechanisms that contribute to a lack of response to blood-pressure-lowering drugs in adherent patients. The use of biomarkers to identify patients with early target organ damage and new technologies, such as renal nerve stimulation, to predict blood pressure responses to renal denervation could aid the selection of patients who might benefit from device therapies.

  9. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, Leendert H.; de Vries, Aiko P. J.; van Son, Willem J.; Homan van der Heide, Jaap J.; Ploeg, Rutger J.; Gansevoort, Ron T.; de Jong, Paul E.; Gans, Rijk O. B.; Bakker, Stephan J. L.

    2005-01-01

    The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and

  10. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, LH; De Vries, APJ; Van Son, WJ; Van Der Heide, JJH; Ploeg, RJ; Gansevoort, RT; De Jong, PE; Gans, ROB; Bakker, SJL

    2005-01-01

    OBJECTIVE - The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS - Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin

  11. Is the sex hormone binding globulin related to preeclampsia independent of insulin resistance

    International Nuclear Information System (INIS)

    Rahmanian, M.; Salari, Z.; Mirmohammadkhani, M.; Ghorbani, R.

    2014-01-01

    Objective: To evaluate the association between Sex Hormone Binding Globulin and preeclampsia in Iranian women considering the probable confounding effect of insulin resistance. Methods: The case-control study was conducted at the Semnan University of Medical Sciences, Iran, and comprised pregnant women who received prenatal care at Amiralmomenin Hospital in 2011. Cases represented patients admitted because of preeclampsia, while controls were randomly selected eligible pregnant women without hypertension and/or proteinuria. Fasting blood sugar and insulin were assessed for all participants as well as their blood concentration of Sex Hormone Binding Globulin. The Homeostasis Model Assessment of Insulin Resistance Score was used. The correlation between dependant and independent variables was reported by crude and adjusted odds ratio applying logistic regression models. SPSS 16.0 was used for statistical analysis. Results: Of the 100 pregnant women in the study, 45(45%) were cases. Insulin resistance was found to be significantly more frequent in the cases compared to the controls (adjusted odds ratio=2.78; 95% Confidence Interval: 1.11, 6.90; p<0.01). There was a significant reverse correlation between level of Sex Hormone Binding Globulin in blood and being a case of preeclampsia (adjusted odds ratio=0.99; 95% Confidence Interval: 0.98, 1.00; p=0.04). Conclusion: Independent of insulin resistance, every 1nmol/l increase in Sex Hormone Binding Globulin, decreases the odds of preeclampsia by 1%, notifying Sex Hormone Binding Globulin as an important biomarker about its etiology and prediction. (author)

  12. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  13. Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

    OpenAIRE

    Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

    2013-01-01

    OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measur...

  14. Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity.

    Science.gov (United States)

    Hellgren, Margareta I; Daka, Bledar; Jansson, Per-Anders; Lindblad, Ulf; Larsson, Charlotte A

    2015-07-01

    to assess how well insulin resistance predicts cardiovascular disease (CVD) in non-diabetic men and women and to explore the influence of physical activity. in this prospective study 2563 men and women without diabetes were examined with an oral glucose tolerance test, anthropometric measurements and blood pressure assessment. Questionnaires about lifestyle and physical activity were completed. Insulin resistance was estimated by fasting concentrations of plasma insulin and by HOMA index for insulin resistance. Participants were followed up for cardiovascular morbidity and mortality during an 8-year period, using information from the National Swedish Inpatient and Mortality registers. at follow-up, HOMAir predicted CVD morbidity in males (50 events) and females (28 events) combined (HRage/sex-adj 1.4, 95% CI 1.1-1.7); however, when stratified by gender HOMAir was predictive solely in men (HRage-adj 1.8, 95% CI 1.3-2.4), whereas no association was found in women (HRage-adj 1.1, 95% CI 0.8-1.5). When stratifying the data for high and low physical activity, the predictive value of insulin resistance became stronger in sedentary men (HRage-adj 2.3, 95% CI 1.5-3.4) but was abolished in men performing moderate to vigorous physical activity (HRage-adj 1.0, 95% CI 0.6-1.6). The results remained when step-wise adjusted also for BMI, ApoB/ApoA1 and hypertension, as well as for smoking, alcohol consumption and education. Outcome for fasting plasma insulin was similar to HOMAir. insulin resistance predicts CVD in the general population; however, men may be more vulnerable to increased insulin resistance than women, and physically inactive men seem to be at high risk. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. How does brain insulin resistance develop in Alzheimer's disease?

    Science.gov (United States)

    De Felice, Fernanda G; Lourenco, Mychael V; Ferreira, Sergio T

    2014-02-01

    Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  16. The effect of low-dose spironolactone on resistant hypertension

    DEFF Research Database (Denmark)

    Engbaek, Mette; Hjerrild, Mette; Hallas, Jesper

    2010-01-01

    with three classes of antihypertensive drugs. The effect on blood pressure was estimated by office measurements together with serum potassium and adverse effects. The data were analyzed retrospectively. A total of 544 patients were identified; 200 were excluded because of secondary hypertension, other......Our objective was to estimate the effect of addition of low-dose spironolactone to previous antihypertensive therapy in patients with resistant hypertension. Patients had 25 to 50 mg of spironolactone once daily added to the treatment of hypertension that was uncontrolled despite previous treatment...... indications for spironolactone than hypertension, previous antihypertensive therapy with less than three drugs unless demonstrated intolerance to a third drug, insufficient compliance, and lack of follow-up data. Thus, 344 cases were included in the analysis. The population was 62.1 ± 12.8 years old, 45...

  17. Insulin resistance, insulin response, and obesity as indicators of metabolic risk

    DEFF Research Database (Denmark)

    Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W

    2007-01-01

    CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308......-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P

  18. Studies of insulin resistance in congenital generalized lipodystrophy

    DEFF Research Database (Denmark)

    Søvik, O; Vestergaard, H; Trygstad, O

    1996-01-01

    suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action......, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did...... not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely...

  19. Investigation of pancreas indocrine function in order to reveal subclinical insulin resistence in women with acne

    OpenAIRE

    Filippova, T.; Rudykh, N.; Shevchuk, A.

    2008-01-01

    Changed glycemic curves and indices of insulin resistance, the increase of insulin basal level in comparison with healthy persons, presence of antibodies to insulin antigen, decrease of level sex hormone bilding globulin were revealed in patients with acne. It can be considered as sign of formation of subclinical insulin resistance.

  20. Dietary patterns and the insulin resistance phenotype among non-diabetic adults

    Science.gov (United States)

    Background: Information on the relation between dietary patterns derived by cluster analysis and insulin resistance is scarce. Objective: To compare insulin resistance phenotypes, including waist circumference, body mass index, fasting and 2-hour post-challenge insulin, insulin sensitivity index (I...

  1. The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics

    Directory of Open Access Journals (Sweden)

    Parapid Biljana

    2010-01-01

    Full Text Available Introduction. The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective. The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods. The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0, insulin (I0 and lipid panel measurements (TC, HDL, LDL, TG were taken after a 12-hour fasting. Results. The protocol encompassed 40 patients (19 men and 21 women treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis, Group B (18 patients, 45%, with a single-vessel disease and Group C (16 patients, 40%, with multi-vessel disease. Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09, while no significant difference was found for G0, LDL, HDL and TG. Conclusion. Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

  2. Relationship of serum resistin with insulin resistance and obesity

    International Nuclear Information System (INIS)

    Zaidi, S.I.Z.

    2015-01-01

    Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

  3. Role of PTEN in TNFα induced insulin resistance

    International Nuclear Information System (INIS)

    Bulger, David A.; Conley, Jermaine; Conner, Spencer H.; Majumdar, Gipsy; Solomon, Solomon S.

    2015-01-01

    Aims/hypothesis: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). Methods: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. Results: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. Discussion: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpic (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2

  4. Role of PTEN in TNFα induced insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Bulger, David A. [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge CB2 0QQ (United Kingdom); National Institute of Diabetes & Digestive & Kidney Disease, National Institutes of Health, Bethesda, MD 20892 (United States); Conley, Jermaine [Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Conner, Spencer H.; Majumdar, Gipsy [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Solomon, Solomon S., E-mail: ssolomon@uthsc.edu [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States)

    2015-06-05

    Aims/hypothesis: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). Methods: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. Results: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. Discussion: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpic (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2.

  5. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    Science.gov (United States)

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519

  6. Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance

    International Nuclear Information System (INIS)

    McElduff, A.; Hedo, J.A.; Taylor, S.I.; Roth, J.; Gorden, P.

    1984-01-01

    The insulin receptor degradation rate was examined in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. The insulin receptors were surface labeled using Na 125 I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup

  7. Insulin resistance and postreceptor changes of liver metabolism in fat-fed mice

    DEFF Research Database (Denmark)

    Hedeskov, Carl Jørgen; Capito, Kirsten; Hansen, Svend Erik

    1992-01-01

    Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet......Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet...

  8. Cancer-drug induced insulin resistance : Innocent bystander or unusual suspect

    NARCIS (Netherlands)

    Ariaans, G.; de Jong, S.; Gietema, J. A.; Lefrandt, J. D.; de Vries, E. G. E.; Jalving, M.

    Epidemiological and experimental evidence strongly suggests an association between type 2 diabetes mellitus and cancer. Insulin resistance, causing hyperinsulinaemia and eventually hyperglycaemia, appears to increase cancer incidence and disease progression. In addition, insulin resistance seems to

  9. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.; et al.,

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  10. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, Karin B.; Smit, Johannes W. A.; den Heijer, Martin; Middeldorp, Saskia; Rippe, Ralph C. A.; le Cessie, Saskia; de Koning, Eelco J. P.; Jukema, J. W.; Rabelink, Ton J.; de Roos, Albert; Rosendaal, Frits R.; de Mutsert, Renée; Rosendaal, F. R.; de Mutsert, R.; Rabelink, T. J.; Smit, J. W. A.; Romijn, J. A.; Rabe, K. F.; de Roos, A.; le Cessie, S.; Hiemstra, P. S.; Kloppenburg, M.; Huizinga, T. W. J.; Pijl, H.; Tamsma, J. T.; de Koning, E. J. P.; Assendelft, W. J. J.; Reitsma, P. H.; van Dijk, K. Willems; de Vries, A. P. J.; Lamb, H. J.; Jazet, I. M.; Dekkers, O. M.; Biermasz, N. R.; Cobbaert, C. M.; Heijer, M. den; Dekker, J. M.; Penninx, B. W.

    2013-01-01

    The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  11. Skeletal muscle lipid metabolism in exercise and insulin resistance

    DEFF Research Database (Denmark)

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

  12. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    DEFF Research Database (Denmark)

    Bjerre, M.; Kistorp, C.; Hansen, T.K.

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  13. Associations of erythrocyte fatty acid patterns with insulin resistance

    Science.gov (United States)

    Background: Synergistic and/or additive effects on cardiometabolic risk may be missed by examining individual fatty acids (FA). A pattern analysis may be a more useful approach. As well, it remains unclear whether erythrocyte fatty acid composition relates to insulin resistance among Hispanic/Latino...

  14. Insulin resistance, metabolic syndrome, and lipids in African women

    African Journals Online (AJOL)

    2016-01-27

    Jan 27, 2016 ... high‑density lipoprotein (TG/HDL), total cholesterol (TC)/HDL, and atherogenic index of ... Key words: Insulin resistance, metabolic syndrome, triglycerides, women ... been reported that a TG/HDL ratio of >3.0 is predictive of.

  15. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    Science.gov (United States)

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  16. Alloxan-induced and Insulin-resistant Diabetes Mellitus affect ...

    African Journals Online (AJOL)

    The purpose of this study was to determine the effects of diabetes mellitus and insulin resistance on semen parameters, histology of reproductive organs and serum concentrations of testosterone and luteinizing hormone (LH). Male Sprague-Dawley rats weighing 180 - 200g were made diabetic by intravenous injection of ...

  17. Acanthosis nigricans: A flag for insulin resistance | Venkatswami ...

    African Journals Online (AJOL)

    Objectives: Acanthosis nigricans refers to the velvety, black hyperpigmentation seen in the flexures. It is a cutaneous marker for insulin resistance (IR), some metabolic disorders and rarely malignancy. When secondary to IR, it is asymptomatic, except for the hyperpigmentation. The neck is the most accessible and easiest to ...

  18. Evidence to Support a Putative Role for Insulin Resistance in ...

    African Journals Online (AJOL)

    Introduction: The primary cause of morbidity and mortality in the renal patient is a cardiovascular event. Insulin resistance (IR) contributes to this event by increasing cardiovascular disease (CVD) and accelerating rates of decline in kidney function. Here we review the historical background of IR in patients with chronic ...

  19. Assessing Psychological Insulin Resistance in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Holmes-Truscott, Elizabeth; Pouwer, F; Speight, Jane

    2017-01-01

    PURPOSE OF REVIEW: This study aims to examine the operationalisation of 'psychological insulin resistance' (PIR) among people with type 2 diabetes and to identify and critique relevant measures. RECENT FINDINGS: PIR has been operationalised as (1) the assessment of attitudes or beliefs about...

  20. Neuroendocrinology of insulin resistance : metabolic and endocrine aspects of adiposity

    NARCIS (Netherlands)

    van Dijk, G; de Vries, K; Benthem, L; Nyakas, C; Buwalda, B; Scheurink, AJW

    2003-01-01

    Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly

  1. Dopamine D2 receptors in the pathophysiology of insulin resistance

    NARCIS (Netherlands)

    Leeuw van Weenen, Judith Elisabeth de

    2011-01-01

    Extensive literature links the dopamine receptor D2 to insulin resistance and diabetes mellitus type 2. However, many aspects of the functional relationship remain unclear. In this thesis we focused on unraveling the characteristics of the interplay between dopamine D2 receptors and glucose

  2. Adipocytokine Associations with Insulin Resistance in British South Asians

    Directory of Open Access Journals (Sweden)

    D. R. Webb

    2013-01-01

    Full Text Available Aims. Adipocytokines are implicated in the pathogenesis of type 2 diabetes and may represent identifiable precursors of metabolic disease within high-risk groups. We investigated adiponectin, leptin, and TNF-α and assessed the contribution of these molecules to insulin resistance in south Asians. Hypothesis. South Asians have adverse adipocytokine profiles which associate with an HOMA-derived insulin resistance phenotype. Methods. We measured adipocytokine concentrations in south Asians with newly diagnosed impaired glucose tolerance or Type 2 Diabetes Mellitus in a case-control study. 158 (48.5% males volunteers aged 25–75 years with risk factors for diabetes but no known vascular or metabolic disease provided serum samples for ELISA and bioplex assays. Results. Total adiponectin concentration progressively decreased across the glucose spectrum in both sexes. A reciprocal trend in leptin concentration was observed only in south Asian men. Adiponectin but not leptin independently associated with HOMA-derived insulin resistance after logistic multivariate regression. Conclusion. Diasporic south Asian populations have an adverse adipocytokine profile which deteriorates further with glucose dysregulation. Insulin resistance is inversely associated with adiponectin independent of BMI and waist circumference in south Asians, implying that adipocytokine interplay contributes to the pathogenesis of metabolic disease in this group.

  3. Is Insulin Resistance an Intrinsic Defect in Asian Polycystic Ovary Syndrome?

    OpenAIRE

    Lee, Hyejin; Oh, Jee-Young; Sung, Yeon-Ah; Chung, Hyewon

    2013-01-01

    Purpose Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and obesity is known to worsen insulin resistance. Many metabolic consequences of PCOS are similar to those of obesity; therefore, defining the cause of insulin resistance in women can be difficult. Our objective was to clarify the factors contributing to insulin resistance in PCOS. Materials and Methods We consecutively recruited 144 women with PCOS [age: 26?5 yr, body mass...

  4. Increased systemic vascular resistance in neonates with pulmonary hypertension.

    Science.gov (United States)

    Milstein, J M; Goetzman, B W; Riemenschneider, T A; Wennberg, R P

    1979-11-01

    The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

  5. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    International Nuclear Information System (INIS)

    Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

    2014-01-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS

  6. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance

  7. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Lippi, Cristina; Casale, Raffaele; Properzi, Giuliana; Blumberg, Jeffrey B; Ferri, Claudio

    2008-09-01

    Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC

  8. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

    Science.gov (United States)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

  9. Traumatic brain injury and obesity induce persistent central insulin resistance.

    Science.gov (United States)

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Association of Insulin Resistance and Hematologic Parameters: Study of a Middle-aged and Elderly Chinese Population in Taiwan

    Directory of Open Access Journals (Sweden)

    Liang-Kung Chen

    2006-06-01

    Conclusion: Elevated WBC count but not RBC count was significantly associated with insulin resistance and glycemic metabolism. The relationship between platelet count and insulin resistance deserves further investigations.

  11. Anaesthesia generates neuronal insulin resistance by inducing hypothermia

    Directory of Open Access Journals (Sweden)

    Sutherland Calum

    2008-10-01

    Full Text Available Abstract Background Anaesthesia is commonly employed prior to surgical investigations and to permit icv injections in rodents. Indeed it is standard practise in many studies examining the subsequent actions of hormones and growth factors on the brain. Recent evidence that the basal activity of specific intracellular signalling proteins can be affected by anaesthesia prompted us to examine the effect of anaesthesia not only on the basal activity but also the insulin sensitivity of the major insulin signalling pathways. Results We find that urethane- and ketamine-induced anaesthesia results in rapid activation of the phosphatidylinositol (PI 3-kinase-protein kinase B (PKB signalling pathway in the brain, increases tau phosphorylation while at the same time reducing basal activity of the Ras-ERK pathway. Subsequent injection of insulin does not alter the activity of either the PI 3-kinase or ERK signalling pathways, indicating a degree of neuronal molecular insulin resistance. However, if body temperature is maintained during anaesthesia then there is no alteration in the basal activity of these signalling molecules. Subsequent response of both pathways to insulin injection is restored. Conclusion The data is consistent with a hypothermia related alteration in neuronal signalling following anaesthesia, and emphasises the importance of maintaining the body temperature of rodents when monitoring insulin (or growth factor/neurotrophic agent action in the brain of anesthetised rodents.

  12. Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

    NARCIS (Netherlands)

    Li, Naishi; Fu, Jingyuan; Koonen, Debby P.; Kuivenhoven, Jan Albert; Snieder, Harold; Hofker, Marten H.

    Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated.

  13. A novel botanical formula prevents diabetes by improving insulin resistance.

    Science.gov (United States)

    Kan, Juntao; Velliquette, Rodney A; Grann, Kerry; Burns, Charlie R; Scholten, Jeff; Tian, Feng; Zhang, Qi; Gui, Min

    2017-07-05

    Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM. Cell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load. Fenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula. A novel botanical formula containing standardized

  14. Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Bruno Melo Carvalho

    2013-01-01

    Full Text Available Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gut microbiota in the pathophysiology of obesity and type 2 diabetes, which is promoted by a bacterial diversity shift mediated by overnutrition. Whole bacteria, their products, and metabolites undergo increased translocation through the gut epithelium to the circulation due to degraded tight junctions and the consequent increase in intestinal permeability that culminates in inflammation and insulin resistance. Several strategies focusing on modulation of the gut microbiota (antibiotics, probiotics, and prebiotics are being experimentally employed in metabolic derangement in order to reduce intestinal permeability, increase the production of short chain fatty acids and anorectic gut hormones, and promote insulin sensitivity to counteract the inflammatory status and insulin resistance found in obese individuals.

  15. Association of fasting glucagon and proinsulin concentrations with insulin resistance

    DEFF Research Database (Denmark)

    Ferrannini, E; Muscelli, E; Natali, A

    2007-01-01

    AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic......, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin...

  16. Insulin-resistance and lipids metabolism in women at menopause

    Directory of Open Access Journals (Sweden)

    Marina Dmitrуina Gresko

    2018-01-01

    Full Text Available The article describes lipid metabolism in women during premenopausal and considered their relationship with the level of insulin sensitivity and abdominal obesity. Examined 20 women aged 46-48 years, with fixed transition to pre-menopause on the bases of menstrual cycle dysfunction or amenorrhea during a year as well as a decrease of visualized follicular reserve according to the results of ultrasonic examination of the organs of the small pelvis, were involved into investigation. Body mass increase with abdominal obese formation and disorders of the lipid metabolism against a background of insulin resistance is observed in women during pre-menopause against a background of sexual hormones deficiency.

  17. Nutrient Excess in AMPK Downregulation and Insulin Resistance

    OpenAIRE

    Coughlan, Kimberly A.; Valentine, Rudy J.; Ruderman, Neil B.; Saha, Asish K.

    2013-01-01

    It is well established that chronic exposure to excess nutrients leads to insulin resistance (IR) in skeletal muscle. Since skeletal muscle is responsible for 70-80% of insulin-stimulated glucose uptake, skeletal muscle IR is a key pathological component of type 2 diabetes (T2D). Recent evidence suggests that inhibition of the nutrient-sensing enzyme AMP-activated protein kinase (AMPK) is an early event in the development of IR in response to high glucose, branched chain amino acids (BCAA), o...

  18. Renal denervation: a new therapeutic approach for resistant hypertension.

    Science.gov (United States)

    Cao, Longxing; Fu, Qiang; Wang, Binghui; Li, Zhiliang

    2014-01-01

    To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

  19. Antihypertensive drug use in resistant and nonresistant hypertension and in controlled and uncontrolled resistant hypertension.

    Science.gov (United States)

    de la Sierra, Alejandro; Armario, Pedro; Oliveras, Anna; Banegas, José R; Gorostidi, Manuel; Vinyoles, Ernest; de la Cruz, Juan J; Segura, Julián; Ruilope, Luis M

    2018-07-01

    Treatment-resistant hypertension (TRH) is associated with particular clinical features, nonadherence, and suboptimal treatment. We assessed possible associations of antihypertensive drug classes, specific agents inside each class, and types of combinations, with the presence of non-TRH vs. TRH, and with controlled vs. uncontrolled TRH. Comparisons were done in 14 264 patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974 treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591). Associations were adjusted for age, sex, and previous cardiovascular event. In both groups of patients treated with three or with at least four drugs, aldosterone antagonists among drug classes [adjusted odds ratio (OR): 1.82 and 1.41, respectively], and ramipril (OR: 1.28 and 1.30), olmesartan (OR: 1.31 and 1.37), and amlodipine (OR: 1.11 and 1.41) inside each class were significantly associated with blood pressure control (non-TRH or controlled TRH). In patients treated with three drugs, non-TRH was also associated with the use of chlorthalidone (OR: 1.50) and bisoprolol (OR: 1.19), whereas in patients treated with at least four drugs, controlled TRH was significantly associated with the triple combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic (OR: 1.17). The use of aldosterone antagonists is associated with blood pressure control in patients treated with three or more drugs. Similar results are observed with specific agents inside each class, being ramipril, olmesartan, chlorthalidone, amlodipine, and bisoprolol those exhibiting significant results. An increased use of these drugs might probably reduce the burden of TRH.

  20. Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

    OpenAIRE

    Talija Hristovska; Marko R. Cincović; Branislava Belić; Dragica Stojanović; Milanka Jezdimirović; Radojica Đoković; Bojan Toholj

    2017-01-01

    Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA), glucose and insulin concentrations, r...

  1. miRNA Signatures of Insulin Resistance in Obesity.

    Science.gov (United States)

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  2. Dietary approaches to stop hypertension influence on insulin receptor substrate-1gene expression: A randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Marzieh Kafeshani

    2015-01-01

    Full Text Available Background: Insulin receptor substrate (IRS Type 1 is a main substrate for the insulin receptor, controls insulin signaling in skeletal muscle, adipose tissue, and the vascular, so it is an important candidate gene for insulin resistance (IR. We aimed to compare the effects of the Dietary Approaches to Stop Hypertension (DASH and Usual Dietary Advices (UDA on IRS1 gene expression in women at risk for cardiovascular disease. Materials and Methods: A randomized controlled clinical trial was performed in 44 women at risk for cardiovascular disease. Participants were randomly assigned to a UDA diet or the DASH diet. The DASH diet was rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, and sweets, with a total of 2400 mg/day sodium. The UDA diet was a regular diet with healthy dietary advice. Gene expression was assessed by the real-time polymerase chain reaction at the first of study and after 12 weeks. Independent sample t-test and paired-samples t-test were used to compare means of all variables within and between two groups respectively. Results: IRS1 gene expression was increased in DASH group compared with UDA diet (P = 0.00. Weight and waist circumference decreased in DASH group significantly compared to the UDA group (P < 0.05 but the results between the two groups showed no significant difference. Conclusion: DASH diet increased IRS1 gene expression and probably has beneficial effects on IR risks.

  3. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

    Science.gov (United States)

    Peripheral insulin resistance shifts metabolic fuel use away from carbohydrates, and towards lipids, and is most commonly associated with Type 2 diabetes mellitus. However, regulated insulin resistance is an evolved mechanism to preserve glucose for the brain in conditions of high demand or carbohy...

  4. Pure Androgen-Secreting Adrenal Adenoma Associated with Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2013-01-01

    Full Text Available Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed.

  5. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  6. A comprehensive review of an unmet public health issue: resistant hypertension.

    Science.gov (United States)

    Cai, Anping; Feng, Yingqing; Zhou, Yingling

    2017-01-01

    Resistant hypertension is an intractable problem to patients and physicians. In recent decades, a substantial amount of basic and epidemiological studies provide us a vast number of valuable evidence and information about this once elusive disease. Better understanding about this entity could help physicians improve diagnostic and therapeutic accuracy. In present review, therefore, we first will detail the definition and diagnosis of resistant hypertension between cardiology societies, and followed by the information of prevalence of resistant hypertension around the world, and then briefly discuss currently used different nomenclature of resistant hypertension, and finally present diagnostic and therapeutic strategies of resistant hypertension.

  7. Management of patients with resistant hypertension: current treatment options

    Directory of Open Access Journals (Sweden)

    Kumar N

    2013-10-01

    Full Text Available Nilay Kumar,1 David A Calhoun,2 Tanja Dudenbostel21Department of Medicine, 2Division of Cardiovascular Disease, Hypertension and Vascular Biology Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Resistant hypertension (RHTN is an increasingly common clinical problem that is often heterogeneous in etiology, risk factors, and comorbidities. It is defined as uncontrolled blood pressure on optimal doses of three antihypertensive agents, ideally one being a diuretic. The definition also includes controlled hypertension with use of four or more antihypertensive agents. Recent observational studies have advanced the characterization of patients with RHTN. Patients with RHTN have higher rates of cardiovascular events and mortality compared with patients with more easily controlled hypertension. Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renovascular disease, are common in patients with RHTN and often coexist in the same patient. In addition, RHTN is often complicated by metabolic abnormalities. Patients with RHTN require a thorough evaluation to confirm the diagnosis and optimize treatment, which typically includes a combination of lifestyle adjustments, and pharmacologic and interventional treatment. Combination therapy including a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist where warranted is the classic regimen for patients with treatment-resistant hypertension. Mineralocorticoid receptor antagonists like spironolactone or eplerenone have been shown to be efficacious in patients with RHTN, heart failure, chronic kidney disease, and primary aldosteronism. Novel interventional therapies, including baroreflex activation and renal denervation, have shown that both of these methods may be used to lower blood pressure safely, thereby providing exciting and promising new

  8. Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

    Directory of Open Access Journals (Sweden)

    Talija Hristovska

    2017-01-01

    Full Text Available Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA, glucose and insulin concentrations, revised quantitative insulin sensitivity check index and glucose-to-insulin ratio. Niacin supplementation led to a decrease of NEFA concentration and an increase of glucose and insulin concentrations during the first three weeks after calving. Cows in the niacin group which were more resistant to insulin showed higher concentrations of non-esterified fatty acid in comparison with more sensitive cows from the same group, but still lower than the control. The regression analyses suggest the following characteristics of cows supplemented with niacin in comparison with the control group: the insulin response to glucose was more intense; the antilipolytic effect of insulin was lower; insulin efficiency expressed as glucose-to-insulin ratio increase with a decrease in NEFA. The metabolic changes due to niacin supplementation showed a dual influence on the insulin resistance in dairy cows during early lactation: decreased NEFA concentrations led to a decrease in the insulin resistance (due to an increase in insulin efficiency and insulin sensitivity index, but increased concentrations of insulin and glucose possibly caused an increase in the insulin resistance in dairy cows (due to lower insulin sensitivity index and possibly lower antilipolytic effects of insulin.

  9. Genetic markers of insulin resistance in gestational diabetes

    Directory of Open Access Journals (Sweden)

    Tatiana Vasil'evna Sebko

    2009-12-01

    Full Text Available Aim. To search for genetic markers of insulin resistance and impaired insulin secretion in pregnant women with gestational diabetes mellitus (GDM. Materials and methods. A total of 100 healthy pregnant women and 185 patients with GDM were available for examination. 80 patients developedGDM during current pregnancy, in 105 it was diagnosed 4-19 years ago. 25 of the 105 GDM patients had a history of type 2 DM. The following parameterswere measured: beta-cell secretory activity (proinsulin, ITI, C-peptide, total cholesterol (CH, HDL and LDL CH, triglycerides, HbA1c,fasting glycemia. Molecular-genetic DNA testing using PCR included studies of KCNJ 11, TCF7L2, PPARG2, ADIPOQ, ADIPOR1, ADIPOR2gene polymorphism. These genes were chosen based on the published data associating them with disturbed insulin secretion and sensitivity in DM2patient. Results. Pregnant women with GDM and obesity showed elevated IRI and leptin levels compared with controls. This rise was accompanied bymarked insulin resistance in 75% of these patients. In 50% of the healthy women proinsulin and insulin secretion decreased. Obesity in pregnantpatients was associated with significant elevation of proinsulin, IRI, and C-peptyide levels and GDM with Lys/Lys genotype of polymorphous markerGlu23k of KCNJ11 gene, pro and ala allele of polymorphous marker A219T of ADIPOR2 gene. These associations suggest specific genetic featuresof GDM related to impaired insulin secretion and sensitivity. Conclusion. Studies of common genetic nature of GDM and DM2 permit to identify risk groups at the preclinical stage, plan prevention and treatmentof these disorders.

  10. Status of serum adiponectin related to insulin resistance in prediabetics

    International Nuclear Information System (INIS)

    Ahsan, S.; Ahmed, S.D.H.; Nauman, K

    2014-01-01

    Obejctive: To find the status of serum adiponectin in individuals progressing towards Type 2 diabetes mellitus and compare it with normal glucose tolerant subjects to determine the stage where alteration of adiponectin occurred. Methods: The cross-sectional study was carried out at the Department of Biochemistry, Jinnah Postgraduate Medical Centre, Karachi, during January to August 2008. Subjects were invited through various diabetes screening camps. A total of 608 subjects >30 years of age without prior history of diabetes were screened through fasting plasma glucose and 2-hour oral glucose tolerance test. Forty randomly selected pre-diabetic subjects and 40 age and gender-matched subjects were included in the study. Anthropometric measurements were done. Serum insulin and adiponectin were estimated by enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance mathematically. Result: Mean fasting and two-hour plasma glucose, body mass index, waist, hip circumference and blood pressure were significantly raised in pre-diabetics compared to those with normal glucose tolerance. Adiponectin was significantly decreased, while insulin and HOMA-IR were raised significantly in the pre-diabetics. Adiponectin showed significant negative correlation with body mass index (r=-0.31, p=0.005), fasting plasma glucose (r=-0.24, p= 0.032), 2-hour plasma glucose (r=-0.42, p<0.0001)), insulin (r-0.43, p<0.0001) and HOMA-IR (r= -0.43, p<0.0001) and remained significant after adjustment of body mass index, gender and insulin level in pre-diabetics. Conclusion: Adiponectin estimation may help in earlier identification of impending diabetes. However, casual link between adiponectin and pre-diabetes remained unexplored due to the study design and small sample size that warrants longitudinal large-scale studies. (author)

  11. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy.

    Science.gov (United States)

    Oelkrug, Rebecca; Herrmann, Beate; Geissler, Cathleen; Harder, Lisbeth; Koch, Christiane; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Mittag, Jens

    2017-10-01

    Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments. We sought to test the consequences of maternal α1-adrenergic antagonism during pregnancy, which can occur e.g. during hypertension treatment, for the endocrine and metabolic phenotype of the offspring. We treated C57BL/6NCrl female mice with the α1-adrenergic antagonist prazosin during pregnancy and analyzed the male and female offspring for endocrine and metabolic abnormalities. Our data revealed that maternal α1-adrenergic blockade caused dwarfism, elevated body temperature, and insulin resistance in male offspring, accompanied by reduced IGF-1 serum concentrations as the result of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently identified increased CpG DNA methylation at the transcriptional start site of the alternative Ghr promotor caused by the maternal treatment, which showed a strong inverse correlation to hepatic Ghr expression. Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  12. Mild Caloric Restriction Decreases Insulin Requirements in Patients With Type 2 Diabetes and Severe Insulin Resistance.

    Science.gov (United States)

    Meehan, Cristina Adelia; Cochran, Elaine; Mattingly, Megan; Gorden, Phillip; Brown, Rebecca J

    2015-07-01

    Type 2 diabetes (T2D) affects ~10% of the US population, a subset of whom have severe insulin resistance (SIR) (>200 units/d). Treatment of these patients with high-dose insulin presents logistical and compliance challenges. We hypothesized that mild caloric restriction would reduce insulin requirements in patients with T2D and SIR.This was a retrospective study at the National Institutes of Health Clinical Center. Inclusion criteria were as follows: T2D, and insulin dose >200 units/d or >2 units/kg/d. The intervention consisted of mild caloric restriction during a 3 to 6-day hospitalization. The major outcomes were change in insulin dose and blood glucose from admission to discharge.Ten patients met inclusion criteria. Baseline glycated hemoglobin A1c was 10.0 ± 1.6% and body mass index 38.8 ± 9.0 kg/m. Food intake was restricted from 2210 ± 371 kcal/d preadmission to 1810 ± 202 during the hospital stay (16.5% reduction). Insulin dose decreased from 486 ± 291 units/d preadmission to 223 ± 127 at discharge (44% reduction, P = 0.0025). Blood sugars decreased nonsignificantly in the fasting state (from 184 ± 85 to 141 ± 42, P = 0.20), before lunch (239 ± 68 to 180 ± 76, P = 0.057), and at bedtime (212 ± 95 to 176 ± 48, P = 0.19), and significantly decreased before dinner (222 ± 92 to 162 ± 70, P = 0.016).Mild caloric restriction, an accessible and affordable intervention, substantially reduced insulin doses in patients with T2D and SIR. Further studies are needed to determine if the intervention and results are sustainable outside of a hospital setting.

  13. Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

    International Nuclear Information System (INIS)

    Bai Jing; Tian Yaping; Guo Duo

    2007-01-01

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG 2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3 H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3 H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3 H-D-glucose in IR cells was significantly lower than that in the control cells(P 3 H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3 H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

  14. Should insulin resistance be screened in lean hirsute women?

    Science.gov (United States)

    Arduc, Ayse; Sarıcam, Orkun; Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Tutuncu, Yasemin Ates; Isik, Serhat; Berker, Dilek; Sennaroglu, Engin; Guler, Serdar

    2015-04-01

    The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 ± 6.1 versus 26.26 ± 4.6years; BMI 21.79 ± 1.7 versus 22.02 ± 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p  2, FGIR lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients.

  15. Fatty acid metabolism, energy expenditure and insulin resistance in muscle.

    Science.gov (United States)

    Turner, Nigel; Cooney, Gregory J; Kraegen, Edward W; Bruce, Clinton R

    2014-02-01

    Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action.

  16. Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases.

    Science.gov (United States)

    Kim, Han Na; Fesseha, Betiel; Anzaldi, Laura; Tsao, Allison; Galiatsatos, Panagis; Sidhaye, Aniket

    2018-01-01

    Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates. We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen. Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Matsuda-DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno-Sobetsu study.

    Science.gov (United States)

    Furugen, M; Saitoh, S; Ohnishi, H; Akasaka, H; Mitsumata, K; Chiba, M; Furukawa, T; Miyazaki, Y; Shimamoto, K; Miura, T

    2012-05-01

    Here we examined whether the Matsuda-DeFronzo insulin sensitivity index (ISI-M) is more efficient than the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing risk of hypertension. Cross-sectional and longitudinal analyses were conducted using normotensive subjects who were selected among 1399 subjects in the Tanno-Sobetsu cohort. In the cross-sectional analysis (n=740), blood pressure (BP) level was correlated with HOMA-IR and with ISI-M, but correlation coefficients indicate a tighter correlation with ISI-M. Multiple linear regression analysis adjusted by age, sex, body mass index (BMI) and serum triglyceride level (TG) showed contribution of ISI-M and fasting plasma glucose, but not of HOMA-IR. In the longitudinal analysis (n=607), 241 subjects (39.7%) developed hypertension during a 10-year follow-up period, and multiple logistic regression indicated that age, TG, systolic BP and ISI-M, but not HOMA-IR, were associated with development of hypertension. In subjects HOMA-IR. Non-hepatic IR may be a determinant, which is independent of TG, BP level and BMI, of the development of hypertension.

  18. Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

    DEFF Research Database (Denmark)

    Høeg, Louise D; Sjøberg, Kim Anker; Jeppesen, Jacob

    2011-01-01

    than men. We therefore hypothesized that women would be less prone to lipid induced insulin resistance. Research and design methods: Insulin sensitivity of whole body and leg glucose disposal was studied in 16 young well matched healthy men and women infused with intralipid or saline for 7h. Muscle...... ratio was decreased by intralipid. Conclusion: Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation or direct inhibition of glucose......AbstractObjective: We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism...

  19. Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes

    DEFF Research Database (Denmark)

    Caruso, Michael; Ma, Danjun; Msallaty, Zaher

    2014-01-01

    Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal transduction. Perturbations involving IRS1 complexes may lead to the development of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known about the proteins that interact with IRS1 in humans under health...... in obesity and T2D in humans, provides new insights into the molecular mechanism of insulin resistance and identifies new targets for T2D drug development....... and disease conditions. We used a proteomic approach to assess IRS1 interaction partners in skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant nondiabetic control subjects (OCs), and participants with T2D before and after insulin infusion. We identified 113 novel endogenous IRS1...

  20. Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Pedersen, O

    2001-01-01

    Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment...

  1. Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

    Science.gov (United States)

    Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

    2016-01-01

    Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

  2. Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance

    DEFF Research Database (Denmark)

    Eriksen, Marie; Jensen, David H; Tribler, Siri

    2015-01-01

    . In addition, first-phase insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase insulin responses at 7 mmol/l. RESULTS: After dexamethasone treatment, all 19 participants had increased insulin resistance (HOMA-IR and insulin sensitivity index [M/I] values) and 2 h plasma glucose...

  3. Peroxynitrite mediates muscle insulin resistance in mice via nitration of IRβ/IRS-1 and Akt

    International Nuclear Information System (INIS)

    Zhou Jun; Huang Kaixun

    2009-01-01

    Accumulating evidence suggests that peroxynitrite (ONOO - ) is involved in the pathogenesis of insulin resistance. In the current study, we investigated whether insulin resistance in vivo could be mediated by nitration of proteins involved in the early steps of the insulin signal transduction pathway. Exogenous peroxynitrite donated by 3-morpholinosydnonimine hydrochloride (SIN-1) induced in vivo nitration of the insulin receptor β subunit (IRβ), insulin receptor substrate (IRS)-1, and protein kinase B/Akt (Akt) in skeletal muscle of mice and dramatically reduced whole-body insulin sensitivity and muscle insulin signaling. Moreover, in high-fat diet (HFD)-fed insulin-resistant mice, we observed enhanced nitration of IRβ and IRS-1 in skeletal muscle, in parallel with impaired whole-body insulin sensitivity and muscle insulin signaling. Reversal of nitration of these proteins by treatment with the peroxynitrite decomposition catalyst FeTPPS yielded an improvement in whole-body insulin sensitivity and muscle insulin signaling in HFD-fed mice. Taken together, these findings provide new mechanistic insights for the involvement of peroxynitrite in the development of insulin resistance and suggest that nitration of proteins involved in the early steps of insulin signal transduction is a novel molecular mechanism of HFD-induced muscle insulin resistance.

  4. Insulin-resistance HCV infection-related affects vascular stiffness in normotensives.

    Science.gov (United States)

    Perticone, Maria; Maio, Raffaele; Tassone, Eliezer Joseph; Tripepi, Giovanni; Di Cello, Serena; Miceli, Sofia; Caroleo, Benedetto; Sciacqua, Angela; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

    2015-01-01

    BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. RESULTS. HCV(+) patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P direct correlation between HOMA and pulse wave velocity in HCV(+) patients, similar to that observed in hypertensives. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Fucosterol activates the insulin signaling pathway in insulin resistant HepG2 cells via inhibiting PTP1B.

    Science.gov (United States)

    Jung, Hyun Ah; Bhakta, Himanshu Kumar; Min, Byung-Sun; Choi, Jae Sue

    2016-10-01

    Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. This study investigated the modulatory effects of fucosterol on the insulin signaling pathway in insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B (PTP1B). In addition, molecular docking simulation studies were performed to predict binding energies, the specific binding site of fucosterol to PTP1B, and to identify interacting residues using Autodock 4.2 software. Glucose uptake was determined using a fluorescent D-glucose analogue and the glucose tracer 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling pathway was detected by Western blot analysis. We found that fucosterol enhanced insulin-provoked glucose uptake and conjointly decreased PTP1B expression level in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 µM in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest that fucosterol stimulates glucose uptake and improves insulin resistance by downregulating expression of PTP1B and activating the insulin signaling pathway. Thus, fucosterol has potential for development as an anti-diabetic agent.

  6. [Factors associated with insulin resistence in rural populations].

    Science.gov (United States)

    Mendes, Larissa Loures; Gazzinelli, Andréa; Velásquez-Meléndez, Gustavo

    2009-04-01

    This study explores the relations of anthropometric, body composition assessments, biochemical and hemodynamic parameters with insulin resistance in two rural communities. Sample was composed by adults aged 18 or older, both sexes. Participants were excluded if pregnant and diabetic. Data collection included demographic lifestyle, hemodynamic, anthropometric and biochemical variables. From the 567 subjects, 50.4% were men and 49.6%, women. Most of the sample was non-white (75.7%), lived with partner (69.3%) and had low educational level. Overweight and obesity prevalences were 17.4% and 5.5%, respectively. Multivariate analysis found risk factors associated to insulin resistance for non-diabetic adults with low income and educational level: overweight, obesity, elevated waist-to-hip ratio, C-reactive protein and skin color.

  7. Resistance training, insulin sensitivity and muscle function in the elderly

    DEFF Research Database (Denmark)

    Dela, Flemming; Kjaer, Michael

    2006-01-01

    Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes......, and likewise to improve muscle strength in both elderly healthy individuals and in elderly individuals with chronic disease. The increased strength is coupled to improved function and a decreased risk for fall injuries and fractures. Elderly individuals have preserved the capacity to improve muscle strength...... are associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes...

  8. Microbial Regulation of Glucose Metabolism and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Silke Crommen

    2017-12-01

    Full Text Available Type 2 diabetes is a combined disease, resulting from a hyperglycemia and peripheral and hepatic insulin resistance. Recent data suggest that the gut microbiota is involved in diabetes development, altering metabolic processes including glucose and fatty acid metabolism. Thus, type 2 diabetes patients show a microbial dysbiosis, with reduced butyrate-producing bacteria and elevated potential pathogens compared to metabolically healthy individuals. Furthermore, probiotics are a known tool to modulate the microbiota, having a therapeutic potential. Current literature will be discussed to elucidate the complex interaction of gut microbiota, intestinal permeability and inflammation leading to peripheral and hepatic insulin resistance. Therefore, this review aims to generate a deeper understanding of the underlying mechanism of potential microbial strains, which can be used as probiotics.

  9. Transcapillary escape rate of albumin in hypertensive patients with type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Feldt-Rasmussen, B

    1993-01-01

    . The systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1--eleven healthy control subjects. Group 2--ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin......Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure...... excretion rate: 30-300 mg/24 h) and normal blood pressure. Group 3--eleven non-diabetic patients with essential hypertension. Group 4--nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (diabetic patients with nephropathy (urinary...

  10. Relationship between insulin resistance and plasma vitamin D in adults

    Directory of Open Access Journals (Sweden)

    Badawi A

    2014-07-01

    Full Text Available Alaa Badawi,1 Suzan Sayegh,2 Eman Sadoun,3 Mohamed Al-Thani,2 Paul Arora,4 Pierre S Haddad51Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada; 2Department of Public Health, 3Clinical Research Division, Supreme Council of Health, Doha, Qatar; 4Dalla Lana School of Public Health, University of Toronto, ON, Canada; 5Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, QC, CanadaAbstract: A recent relationship between vitamin D deficiency and the risk of type 2 diabetes mellitus (T2DM and insulin resistance has been established through several studies. Research suggests a correlation between serum vitamin D and glycemic status measures. The aim of this study was to investigate the relationship between the plasma vitamin D levels (25[OH]D and the factors linked to insulin resistance in a representative sample of Canadians ranging in age from 16–79 years. Data were used from the Canadian Health Measures Survey where direct measures of health and wellness were reported from 1,928 subjects. These data were gathered from March 2007–February 2009 at 15 sites selected through a multistage sampling strategy. An inverse relationship between insulin resistance and plasma vitamin D level in both men and women was observed. This study provides additional evidence for the role of vitamin D in T2DM. If causally associated, the supplementation of vitamin D may help in preventing insulin resistance and subsequent T2DM.Keywords: HOMA-IR, plasma 25(OHD, diabetes

  11. The sites and mechanisms of postoperative insulin resistance

    OpenAIRE

    Nygren, Jonas

    1997-01-01

    The Sites and Mechanisms of Postoperative InsulinResistance by Jonas Nygren, M.D. Departments of Surgery and Endocrinology and Diabetes, Karolinska Hospital and Institute, SE-171 76, Stockholm, Sweden In Sweden with nine million inhabitants, 450,000 operations(outpatients excluded) are performed every year resulting in2,250,000 treatment days in hospital. Surgical operations are part ofthe treatment for 44% of all patients admitted to hospital careoccupying 24% of all ...

  12. Feasibility of catheter ablation renal denervation in "mild" resistant hypertension.

    Science.gov (United States)

    Chen, Shaojie; Kiuchi, Marcio Galindo; Acou, Willem-Jan; Derndorfer, Michael; Wang, Jiazhi; Li, Ruotian; Kollias, Georgios; Martinek, Martin; Kiuchi, Tetsuaki; Pürerfellner, Helmut; Liu, Shaowen

    2017-04-01

    Renal denervation (RDN) has been proposed as a novel interventional antihypertensive technique. However, existing evidence was mainly from patients with severe resistant hypertension. The authors aimed to evaluate the efficacy of RDN in patients with resistant hypertension with mildly elevated blood pressure (BP). Studies of RDN in patients with mild resistant hypertension (systolic office BP 140-160 mm Hg despite treatment with three antihypertensive drugs including one diuretic, or mean systolic BP by 24-hour ambulatory BP measurement [ABPM] 135-150 mm Hg) were included. Two observational and one randomized cohort were identified (109 patients in the RDN group and 36 patients in the control group). Overall, the mean age of patients was 62±10 years, and 69.7% were male. Before-after comparison showed that RDN significantly reduced ABPM as compared with the baseline systolic ABPM, from 146.3±13 mm Hg at baseline to 134.6±14.7 mm Hg at 6-month follow-up and diastolic ABPM from 80.8±9.4 mm Hg at baseline to 75.5±9.8 mm Hg at 6-month follow up (both Phypertension. ©2017 Wiley Periodicals, Inc.

  13. Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages

    Directory of Open Access Journals (Sweden)

    Bryan J. Neth

    2017-10-01

    Full Text Available Metabolic dysfunction is a well-established feature of Alzheimer’s disease (AD, evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D, hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. This association may in part be due to the systemic mitochondrial dysfunction that is common to these pathologies. Accumulating evidence suggests that mitochondrial dysfunction is a significant feature of AD and may play a fundamental role in its pathogenesis. In fact, aging itself presents a unique challenge due to inherent mitochondrial dysfunction and prevalence of chronic metabolic disease. Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.

  14. Obesity, insulin resistance, and type 1 diabetes mellitus.

    Science.gov (United States)

    Polsky, Sarit; Ellis, Samuel L

    2015-08-01

    To summarize recent studies about obesity, insulin resistance, and type 1 diabetes mellitus (T1DM). Overweight and obesity continue to be prevalent among individuals with T1DM. Obesity rates appear to have reached a plateau among children with T1DM in some parts of the world. The risk for development of T1DM is increased by obesity and may occur at an earlier age among obese individuals with a predisposition. Obesity increases the risk for comorbidities among individuals with T1DM, especially metabolic syndrome, and microvascular and macrovascular diseases. Metformin, glucagon-like peptide-1 agonist therapy, sodium glucose cotransporter-2 inhibitor therapy, and bariatric surgery may be beneficial therapies for glucose control, comorbidity management, and obesity among adults with T1DM. Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide). We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

  15. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

  16. Obesity, ectopic lipids, and insulin resistance : Tissue-specific defects in nutrient handling

    NARCIS (Netherlands)

    ter Horst, K.W.

    2017-01-01

    This thesis described studies on the clinical, nutritional, and molecular aspects of insulin resistance in human obesity. We investigated methods for the identification of insulin resistance in high-risk patients and studied the nutritional and molecular mechanisms that may contribute to insulin

  17. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

    Directory of Open Access Journals (Sweden)

    Isao Saito

    2015-09-01

    Full Text Available Background: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods: Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR and Gutt’s insulin sensitivity index (ISI. Pulse was recorded for 5 min, and time-domain heart rate variability (HRV indices were calculated: the standard deviation of normal-to-normal intervals (SDNN and the root mean square of successive difference (RMSSD. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF power, low frequency (LF power, and the LF:HF ratio. Results: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10. Conclusions: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

  18. [Renal denervation a treatment for resistant hypertension: a French experience].

    Science.gov (United States)

    Benamer, H; Mylotte, D; Garcia-Alonso, C; Unterseeh, T; Garot, P; Louvard, Y; Lefevre, T; Morice, M-C

    2013-12-01

    Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFRdenervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (Prenal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. A controlled trial of renal denervation for resistant hypertension.

    Science.gov (United States)

    Bhatt, Deepak L; Kandzari, David E; O'Neill, William W; D'Agostino, Ralph; Flack, John M; Katzen, Barry T; Leon, Martin B; Liu, Minglei; Mauri, Laura; Negoita, Manuela; Cohen, Sidney A; Oparil, Suzanne; Rocha-Singh, Krishna; Townsend, Raymond R; Bakris, George L

    2014-04-10

    Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension. We designed a prospective, single-blind, randomized, sham-controlled trial. Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure. The primary safety end point was a composite of death, end-stage renal disease, embolic events resulting in end-organ damage, renovascular complications, or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70% at 6 months. A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group (Pdenervation group and -4.79±17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups. This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.).

  20. Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

    International Nuclear Information System (INIS)

    Khan, A.; Qayyum, A.; Khan, B.T.

    2017-01-01

    Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice. Study Design: Randomized control trail. Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014. Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartan for four weeks after induction of diabetes. Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation (r-value, 0.92) with significant p-value (0.015) in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive. Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone. (author)

  1. Nutrient sensing and insulin signaling in neuropeptide-expressing immortalized, hypothalamic neurons: A cellular model of insulin resistance.

    Science.gov (United States)

    Fick, Laura J; Belsham, Denise D

    2010-08-15

    Obesity and type 2 diabetes mellitus represent a significant global health crisis. These two interrelated diseases are typified by perturbed insulin signaling in the hypothalamus. Using novel hypothalamic cell lines, we have begun to elucidate the molecular and intracellular mechanisms involved in the hypothalamic control of energy homeostasis and insulin resistance. In this review, we present evidence of insulin and glucose signaling pathways that lead to changes in neuropeptide gene expression. We have identified some of the molecular mechanisms involved in the control of de novo hypothalamic insulin mRNA expression. And finally, we have defined key mechanisms involved in the etiology of cellular insulin resistance in hypothalamic neurons that may play a fundamental role in cases of high levels of insulin or saturated fatty acids, often linked to the exacerbation of obesity and diabetes.

  2. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    Science.gov (United States)

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

    Directory of Open Access Journals (Sweden)

    Iskra Bitoska

    2016-02-01

    CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

  4. Insulin resistance in drug naive patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kostić Smiljana

    2017-01-01

    Full Text Available Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS, the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR and reduced insulin sensitivity (IS in untreated patients with MS could play a role in disease progression and degree of functional disability. Methods. The study included 31 patients with relapsing-remitting (RR MS and 14 healthy controls from the same geographic area matched by age, ethnicity and number of smokers. The glucose tolerance, IS, and IR were examined using an oral glucose tolerance test (OGTT and using basal plasma glucose and insulin levels. The functional disability and disease progression were evaluated by the Expanded Disability Status Scale (EDSS and Multiple Sclerosis Severity Score (MSSS. Results. The MS patients tolerated glucose equally well as the healthy controls. Basal concentrations of insulin were significantly higher in the MS group (p < 0.05, as well as insulin plasma level 30 min after oral glucose load (p < 0.01. The patients with MS had significantly higher values of homeostasis model assessment indexes of IR (HOMA-IR (p = 0.027; p = 0.028. The percentage of IS (HOMA2 %S and whole body IS index (ISI Matsuda showed significantly lower values in the MS patients than in the controls (p = 0.005; p = 0.001. The insulinogenic index in the first 30 min of OGTT was significantly higher in MS patients (p = 0.005. The measures of functional disability and MS progression did not correlate significantly with the investigated parameters of IR and IS indexes. Conclusion. This study demonstrates for the first time the existence of hyperinsulinemia, reduced insulin sensitivity and normal glucose tolerance that indicate the initial

  5. Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

    Directory of Open Access Journals (Sweden)

    Mimi Z Chen

    Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

  6. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

    Science.gov (United States)

    2015-01-01

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

  7. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    2008-03-01

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  8. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

  9. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  10. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism

    OpenAIRE

    Yoon, Mee-Sup

    2016-01-01

    Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or...

  11. Novel and Reversible Mechanisms of Smoking-Induced Insulin Resistance in Humans

    OpenAIRE

    Bergman, Bryan C.; Perreault, Leigh; Hunerdosse, Devon; Kerege, Anna; Playdon, Mary; Samek, Ali M.; Eckel, Robert H.

    2012-01-01

    Smoking is the most common cause of preventable morbidity and mortality in the United States, in part because it is an independent risk factor for the development of insulin resistance and type 2 diabetes. However, mechanisms responsible for smoking-induced insulin resistance are unclear. In this study, we found smokers were less insulin sensitive compared with controls, which increased after either 1 or 2 weeks of smoking cessation. Improvements in insulin sensitivity after smoking cessation...

  12. Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats.

    Science.gov (United States)

    Mikus, Catherine R; Roseguini, Bruno T; Uptergrove, Grace M; Morris, E Matthew; Rector, Randy Scott; Libla, Jessica L; Oberlin, Douglas J; Borengasser, Sarah J; Taylor, Angelina M; Ibdah, Jamal A; Laughlin, Maurice Harold; Thyfault, John P

    2012-11-01

    Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. Insulin signaling and vasoreactivity to insulin (1-1000 μIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p RUN20 (p RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal. © 2012 John Wiley & Sons Ltd.

  13. The establishment of insulin resistance model in FL83B and L6 cell

    Science.gov (United States)

    Liu, Lanlan; Han, Jizhong; Li, Haoran; Liu, Mengmeng; Zeng, Bin

    2017-10-01

    The insulin resistance models of mouse liver epithelial and rat myoblasts cells were induced by three kinds of inducers: dexamethasone, high insulin and high glucose. The purpose is to select the optimal insulin resistance model, to provide a simple and reliable TR cell model for the study of the pathogenesis of TR and the improvement of TR drugs and functional foods. The MTT method is used for toxicity screening of three compounds, selecting security and suitable concentration. We performed a Glucose oxidase peroxidase (GOD-POD) method involving FL83B and L6 cell with dexamethasone, high insulin and high glucose-induced insulin resistance. Results suggested that FL83B cells with dexamethasone-induced (0.25uM) were established insulin resistance and L6 cells with high-glucose (30mM) and dexamethasone-induced (0.25uM) were established insulin resistance.

  14. Renal sympathetic denervation for treatment of resistant hypertension: Egyptian experience.

    Science.gov (United States)

    Hamza, Mohamed; Khamis, Hazem

    2014-08-01

    Among the Egyptian population with essential hypertension, a minority are under control (systolic pressure renal artery radiofrequency (RF) ablation. To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension in Egyptian patients. Patients with essential hypertension unresponsive to at least 3 types of antihypertensive medical therapy (baseline office systolic blood pressure ≥160 mmHg) (n = 55) were enrolled between February 2012 and June 2013 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment to detect any change in office-based measurement of blood pressure. Urine and blood samples were taken to evaluate the effects on renal function. A reduction of mean office blood pressure was seen from 174/103 ± 9/5 mmHg at baseline to 150/91 ± 8/5 mmHg at 6 months follow-up (P = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 vs. 3.37 ± 0.47 ng/mL per hour; P = 0.003), and there were no periprocedural complications, no adverse events, and no change in renal function during the follow-up period. Also, no change was noted in the number of medications after 6 months (3.95 ± 1.64 vs. 3.67 ± 0.72; P = 0.27). In this observational study, catheter-based renal denervation causes sustained blood pressure reduction in patients with resistant hypertension, without serious adverse events. © 2014, Wiley Periodicals, Inc.

  15. Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

    Science.gov (United States)

    Yao, Longbiao; Herlea-Pana, Oana; Heuser-Baker, Janet; Chen, Yitong; Barlic-Dicen, Jana

    2014-01-01

    The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies. PMID:24741577

  16. Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Longbiao Yao

    2014-01-01

    Full Text Available The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies.

  17. Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

    Science.gov (United States)

    Vazquez-Anaya, Guillermo; Martinez, Bridget; Soñanez-Organis, José G; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2017-03-01

    Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T 4 ) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T 4 (8.0 µg/100 g BM/day × 5 weeks). T 4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T 4 -treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T 4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T 4 treatment increased the influx of T 4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T 3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis. © 2017 Society for Endocrinology.

  18. Vitamin D and insulin resistance in postmenopausal Indian women

    Directory of Open Access Journals (Sweden)

    Niti Agarwal

    2014-01-01

    Full Text Available Purpose: The purpose of this study is to investigate the association of the serum 25-hydroxyvitamin D (25-OHD level with markers of insulin resistance (IR in postmenopausal Indian women. Materials and Methods: This was a cross-sectional study, conducted at a Tertiary Care Hospital in New Delhi, India. Seventy one postmenopausal women (mean age 56.3 ± 7.6 years were enrolled. Exclusion criteria were known or newly detected diabetics, subjects with chronic renal failure, chronic liver disease or any other chronic inflammatory condition, chronic smokers and chronic alcoholics. Serum calcium (and albumin for calculating corrected calcium, phosphorus, alkaline phosphatase and 25-OHD were measured as parameters of calcium homeostasis. Fasting blood glucose (FBG, systolic and diastolic blood pressures, body mass index (BMI, fasting serum insulin, calculated glucose insulin ratio (GIR, and homeostatic model assessment of insulin resistance (HOMA-IR were studied as parameters of IR. Data was then analyzed for statistical significance. Results: The mean serum 25-OHD level was 12.73 ± 7.63 ng/ml. The mean BMI was 27.78 ± 5.37 kg/m 2 . The mean calculated GIR was 13.14 ± 9.39 and HOMA-IR was 2.31 ± 1.70. Serum 25-OHD was inversely correlated with BMI (correlation coefficient −0.234, P value 0.050 and with HOMA-IR (correlation coefficient −0.237, P value 0.047. However, when 25-OHD was adjusted for BMI the correlation between 25-OHD and HOMA-IR lost its significance. No correlation was found between serum 25-OHD and any other parameters of IR studied. Conclusions: There is a significant negative linear correlation between 25-OHD and BMI. The significant negative linear correlation between 25-OHD and HOMA-IR was confounded by BMI. There is no correlation between 25-OHD and parameters of IR.

  19. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  20. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Hayato Yanagihara

    2016-07-01

    Full Text Available Although telmisartan, an angiotensin II receptor blocker (ARB, has an agonistic action for proliferator-activated receptor (PPAR-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats. To address the issue, telmisartan (2 mg/kg and olmesartan (2 mg/kg, another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR fed a high fat diet (HFD. HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions.

  1. Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

    Science.gov (United States)

    Vinik, A I; Seino, S; Funakoshi, A; Schwartz, J; Matsumoto, M; Schteingart, D E; Fu, Z Z; Tsai, S T

    1986-04-01

    A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

  2. Differential insulin and steroidogenic signaling in insulin resistant and non-insulin resistant human luteinized granulosa cells-A study in PCOS patients.

    Science.gov (United States)

    Belani, Muskaan; Deo, Abhilash; Shah, Preeti; Banker, Manish; Singal, Pawan; Gupta, Sarita

    2018-04-01

    Insulin resistance (IR) is one of the significant aberrations in polycystic ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and 20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin resistance (NIR). This could possibly be due to defects in the downstream signaling pathways. The study thus aims to unravel insulin and steroidogenic signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs matched controls. Luteinized granulosa cells from 30 controls and 39 PCOS were classified for IR based on a novel method of down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. We evaluated expression of molecules involved in insulin, steroidogenic signaling and lipid metabolism in luteinized granulosa cells followed by analysis of estradiol, progesterone and testosterone in follicular fluid. Protein expression of INSR- β, pIRS (ser 307), PI(3)K, PKC-ζ, pAkt, ERK1/2, pP38MAPK and gene expression of IGF showed differential expression in the two groups. Increased protein expression of PPAR-γ was accompanied by up regulation in SREBP1c, FAS, CPT-1 and ACC-1 genes in PCOS-IR group. Expression of StAR, CYP19A1, 17 β- HSD and 3 β- HSD demonstrated significant decrease along with increase in CYP11A1, FSH-R and LH-R in both the groups. Follicular fluid testosterone increased and progesterone decreased in PCOS-IR group. This study shows how candidate molecules that were differentially expressed, aid in designing targeted therapy against the two phenotypes of PCOS. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Renal denervation in the management of resistant hypertension: current evidence and perspectives.

    Science.gov (United States)

    Jin, Yu; Persu, Alexandre; Staessen, Jan A

    2013-09-01

    Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

  4. Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

    Science.gov (United States)

    Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

    2016-02-01

    Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  5. Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine.

    Science.gov (United States)

    de Giorgis, T; Marcovecchio, M L; Giannini, C; Chiavaroli, V; Chiarelli, F; Mohn, A

    2016-02-01

    Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 μmol/l, p childhood to adolescence (p obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

  6. A short leucocyte telomere length is associated with development of insulin resistance

    DEFF Research Database (Denmark)

    Verhulst, Simon; Dalgård, Christine; Labat, Carlos

    2016-01-01

    AIMS/HYPOTHESIS: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance...... and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs. RESULTS: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age......-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p 

  7. Spironolactone and doxazosin treatment in patients with resistant hypertension.

    Science.gov (United States)

    Rodilla, Enrique; Costa, José A; Pérez-Lahiguera, Francisco; Baldó, Emilio; González, Carmen; Pascual, José M

    2009-02-01

    The aim of this study was to evaluate the use of spironolactone and doxazosin as treatment for patients with resistant hypertension. This retrospective study involved 181 outpatients with resistant hypertension (defined as a failure of blood pressure [BP] control despite treatment with three drugs, one of which was a diuretic) who received additional spironolactone (n=88) or doxazosin (n=93). Mean systolic BP in the spironolactone group fell by 28 mmHg (95% confidence interval [CI], 24-32 mmHg; P< .001) and mean diastolic BP fell by 12 mmHg (95% CI, 9-14 mmHg; P< .001). The corresponding falls in the doxazosin group were 16 mmHg (95% CI, 13-20 mmHg; P< .001) and 7 mmHg (95% CI, 5-9 mmHg; P< .001), respectively. The decrease was significantly greater with spironolactone for both systolic (P< .001) and diastolic (P=.003) pressures. At the end of follow-up, 30% of all patients had achieved BP control, with control being more frequent with spironolactone (39%) than doxazosin (23%; P=.02). Multivariate logistic regression analysis showed that the only factors that significantly influenced the achievement of BP control were diabetes (odds ratio=0.17; 95% CI, 0.08-0.39; P< .001) and baseline systolic BP <165 mmHg (odds ratio=2.56; 95% CI, 1.11-5.90; P=.03). In patients with resistant hypertension, the addition of either spironolactone or doxazosin resulted in a significant decrease in BP, though the decrease appeared to be greater with spironolactone. The presence of diabetes complicated BP control.

  8. A common variation of the PTEN gene is associated with peripheral insulin resistance

    DEFF Research Database (Denmark)

    Grinder-Hansen, L; Ribel-Madsen, R; Wojtaszewski, Jørgen

    2016-01-01

    . RESULTS: The minor G allele of PTEN rs11202614 was associated with elevated fasting plasma insulin levels and a decreased peripheral glucose disposal rate, but not with the hepatic insulin resistance index or insulin secretion measured as the first-phase insulin response and disposition index. The single...... nucleotide polymorphism was not associated with either PI3K or Akt activities. CONCLUSION: A common PTEN variation is associated with peripheral insulin resistance and subsequent risk of developing T2D. However, the association with insulin resistance is not explained by decreased proximal insulin signalling......AIM: Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity by inhibiting the phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (Akt) pathway. This study investigated how a common single nucleotide polymorphism near PTEN, previously associated...

  9. Cardiac Insulin Resistance and MicroRNA Modulators

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2012-01-01

    Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

  10. The prevalence of resistant arterial hypertension and secondary causes in a cohort of hypertensive patients: a single center experience

    Directory of Open Access Journals (Sweden)

    Luigi Petramala

    2017-11-01

    Full Text Available The prevalence of resistant hypertension (RHT still remains unknown. Aim of the study was to investigate in a large cohort of hypertensive patients the prevalence of RHT, and to identify in these patients the secondary forms of arterial hypertension (SH. We enrolled a series of 3685 consecutive hypertensive patients. All patients underwent complete physical examination, laboratory tests, screening for SH. Ambulatory blood pressure monitoring (ABPM was performed to exclude white-coat hypertension. Further, we investigated for any obstructive sleep apnea syndrome (OSA. Only 232 (5.8% hypertensive patients fulfilled criteria for RHT. 91 (39% had a SH; 56 (61% hypertensive patients had a primary aldosteronism, 22 (24% had OSA, 7 (7.7% had a hypercortisolism, and 5 (5.5% had a renovascular hypertension (RVH. Only one patient had adrenal pheochromocytoma. An accurate definition and investigation into RHT is needed. We recommend ABPM to all patients at diagnosis. Finally, all patients must be screened for SH, such as adrenal hypertension, OSA and RVH, especially those who are apparently resistant to polypharmacological treatment.

  11. Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

    Science.gov (United States)

    Hallschmid, M; Schultes, B

    2009-11-01

    Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

  12. Intrauterine insulin resistance in fetuses of overweight mothers.

    Science.gov (United States)

    Liu, Bin; Xu, Yun; Liang, Jian-Ming; Voss, Courtney; Xiao, Huan-Yu; Sheng, Wei-Yang; Sun, Yan-Hong; Wang, Zi-Lian

    2013-01-01

    To investigate the relationship between maternal overweight and fetal insulin resistance. Nineteen overweight and 30 lean pregnant women were recruited in the present study. Maternal and fetal insulin resistance were determined by measuring sex hormone binding globulin (SHBG) concentrations in maternal venous or umbilical cord serum, respectively. Maternal age, gestational age, height, pre-gravidity weight, pre-partum weight, as well as fetal gender, birth weight, birth height, and head circumference were collected as clinical data. Fetuses of overweight mothers had larger birth weight (3.58±0.55kg vs 3.32±0.42, adjusted P=0.006) and lower SHBG concentrations (26.64±3.65 vs 34.36±7.84, adjusted P=0.007) than those of lean mothers after values were adjusted for potential cofactors. Fetal SHBG level was negatively correlated with pre-gravidity body mass index (R=-0.392, adjusted P=0.025) and weight gain during pregnancy (R=-0.332, adjusted P=0.026) even with adjustment for potential cofactors. Among the 29 pregnant women with gestational diabetes mellitus, the overweight mothers had higher H1AC levels than their lean counterparts (6.47±0.44 vs 5.74±0.52, adjusted P=0.004). Intrauterine insulin resistance is more prominent in fetuses of overweight mothers, an effect that is decreased by weight gain control during pregnancy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  13. Triglycerides and glucose index: a useful indicator of insulin resistance.

    Science.gov (United States)

    Unger, Gisela; Benozzi, Silvia Fabiana; Perruzza, Fernando; Pennacchiotti, Graciela Laura

    2014-12-01

    Insulin resistance assessment requires sophisticated methodology of difficult application. Therefore, different estimators for this condition have been suggested. The aim of this study was to evaluate the triglycerides and glucose (TyG) index as a marker of insulin resistance and to compare it to the triglycerides/HDL cholesterol ratio (TG/HDL-C), in subjects with and without metabolic syndrome (MS). An observational, cross-sectional study was conducted on 525 adults of a population from Bahia Blanca, Argentina, who were divided into two groups: with MS (n=89) and without MS (n=436). The discriminating capacities for MS of the TyG index, calculated as Ln (TG [mg/dL] x glucose [mg/dL]/2), and the TG/HDL-C ratio were evaluated. Pre-test probability for MS was 30%. The mean value of the TyG index was higher in the group with MS as compared to the group without MS and its correlation with the TG/HDL-C ratio was good. The cut-off values for MS in the overall population were 8.8 for the TyG index (sensitivity=79%, specificity=86%), and 2.4 for the TG/HDL-C ratio (sensitivity=88%, specificity=72%). The positive likelihood ratios and post-test probabilities for these parameters were 5.8 vs 3.1 and 72% vs 58% respectively. The cut-off point for the TyG index was 8.8 in men and 8.7 in women; the respective values for TG/C-HDL were 3.1 in men and 2.2 in women. The TyG index was a good discriminant of MS. Its simple calculation warrants its further study as an alternative marker of insulin resistance. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  14. The Insulin-Sensitive Side of SHIP2

    Directory of Open Access Journals (Sweden)

    Stephane Schurmans

    2001-01-01

    Full Text Available A substantial and increasing proportion of death and disability in the EU (and elsewhere is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity. Beside type II diabetes, other diseases like obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian syndrome, and acromegaly are indeed associated with insulin resistance [1].

  15. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  16. Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

    OpenAIRE

    de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

    2009-01-01

    Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

  17. Total antioxidant and oxidant status in obese children without insulin resistance

    OpenAIRE

    Ayşegül Doğan Demir; Ufuk Erenberk; İlker Tolga Özgen; Emin Özkaya; Aysel Vahapoğlu Türkmen; M. Ruşen Dündaröz; Özcan Erel

    2014-01-01

    Objective: Oxidative stress in obese children may lead in adulthood serious conditions such as coronary heart diseases or type 2 diabetes mellitus. In childhood oxidative stress is associated with insulin resistance or extreme obesity. In this study, we aimed to evaluate oxidative stress status in moderately obese children without insulin resistance. Methods: A total of 38 obese children (21 male, 17 female) without insulin resistance, mean aged 9.4±3.8 years) and 51 normal weight children...

  18. Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects

    OpenAIRE

    Yamada, Chizumi; Kondo, Masumi; Kishimoto, Noriaki; Shibata, Takeo; Nagai, Yoko; Imanishi, Tadashi; Oroguchi, Takashige; Ishii, Naoaki; Nishizaki, Yasuhiro

    2015-01-01

    Aims/Introduction Elevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma ami...

  19. Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle D; Hedlin, Haley; Stefanick, Marcia L

    2015-01-01

    BACKGROUND: Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. METHODS AND RESULTS: We identified 15,288 women from the Women's Health Initiative Biomarkers....../HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which...

  20. Serum AMH levels and insulin resistance in women with PCOS.

    Science.gov (United States)

    Sahmay, Sezai; Aydogan Mathyk, Begum; Sofiyeva, Nigar; Atakul, Nil; Azemi, Aslı; Erel, Tamer

    2018-05-01

    To compare the serum AMH levels between women with and without insulin resistance (IR) in polycystic ovary syndrome (PCOS). 293 women with PCOS according to the Rotterdam criteria were enrolled into our study. Insulin resistance was diagnosed according to the Homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Women were grouped according to the presence of insulin resistance (IR) (HOMA-IR ≥ 2.5). Serum AMH and other hormones were compared between the IR (+) and IR (-) groups. Additionally, AMH percentiles were (75) constructed; HOMA-IR and BMI values in women with/without IR were compared in different percentiles. Further, HOMA-IR, BMI and AMH values were measured across different PCOS phenotypes. The prevalence of IR was 45%. The prevalence of IR was 57% in women with BMI ≥ 25. Serum AMH levels were not significantly different among women with and without IR. Also, HOMA-IR values were not significant among different AMH percentiles. However, in each AMH percentile BMI were found to be higher in women with IR than in women without IR. The median HOMA-IR values were the highest in women with BMI ≥ 25 in both IR (+) and IR (-) groups. No significant difference was found among PCOS phenotypes in terms of HOMA-IR and BMI. Positive correlations were found between BMI, free testosterone and HOMA-IR. However, no correlation was found between AMH and HOMA-IR. The serum AMH levels between women with IR and without IR in PCOS were not significantly different. Also, we did not reveal a correlation between serum AMH levels and IR in women with PCOS. IR was not correlated with different PCOS phenotypes either. We found a positive correlation between BMI and IR. IR should be investigated in women with PCOS having a BMI ≥ 25, independent of their phenotype or AMH levels. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Protective effects of metformin on neointima formation in insulin resistance

    Directory of Open Access Journals (Sweden)

    Yu V Pankratova

    2013-06-01

    Full Text Available Реферат по материалам статьи Lu J, Ji J, Meng H, Wang D, Jiang B, Liu L, Randell E, Adeli K, Meng QH. The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats. Cardiovasc Diabetol. 2013 Apr 5;12:58. doi: 10.1186/1475-2840-12-58.

  2. Tertiary work-up of apparent treatment-resistant hypertension.

    Science.gov (United States)

    Heimark, Sondre; Eskås, Per Anders; Mariampillai, Julian Eek; Larstorp, Anne Cecilie K; Høieggen, Aud; Fadl Elmula, Fadl Elmula M

    2016-10-01

    Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

  3. [Renal denervation in resistant hypertension: proposal for a common multidisciplinary attitude].

    Science.gov (United States)

    Muller, Olivier; Qanadli, Salah D; Waeber, Bernard; Wuerzner, Grégoire

    2012-05-30

    The prevalence of resistant hypertension ranges between 5-30%. Patients with resistant hypertension are at increased risk of cardiovascular events. Radiofrequency renal denervation is a recent and promising technique that can be used in the setting of resistant hypertension. However, long-term safety and efficacy data are lacking and evidence to use this procedure outside the strict setting of resistant hypertension is missing. The aim of the article is to propose a common work-up for nephrologists, hypertensiologists, cardiologists and interventional radiologists in order to avoid inappropriate selection of patients and a possible misuse of this procedure.

  4. Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

    Science.gov (United States)

    Sawathiparnich, Pairunyar; Weerakulwattana, Linda; Santiprabhob, Jeerunda; Likitmaskul, Supawadee

    2005-11-01

    The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

  5. Insulin resistance and associated factors: a cross-sectional study of bank employees.

    Science.gov (United States)

    Salaroli, Luciane Bresciani; Cattafesta, Monica; Molina, Maria Del Carmen Bisi; Zandonade, Eliana; Bissoli, Nazaré Souza

    2017-04-01

    Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >2.71 for insulin resistance, as established for the adult Brazilian population. It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals.

  6. Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

    Science.gov (United States)

    Ahmed, Naeema; Rashid, Amir; Naveed, Abdul Khaliq; Bashir, Qudsia

    2016-02-01

    To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

  7. Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension

    NARCIS (Netherlands)

    Gerritsen, TA; Bak, AAA; Stolk, RP; Jonker, JJC; Grobbee, DE

    Objective To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension, Design A double-blind randomized,

  8. Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Skøtt, P

    1992-01-01

    The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

  9. Erythrocyte membrane ion transport in offspring of hypertensive parents: effect of acute hyperinsulinemia and relation to insulin action

    Czech Academy of Sciences Publication Activity Database

    Suchánková, G.; Vlasáková, Z.; Zicha, Josef; Vokurková, Martina; Dobešová, Zdenka; Pelikánová, T.

    2002-01-01

    Roč. 967, - (2002), s. 352-362 ISSN 0077-8923 R&D Projects: GA MZd NB6682; GA ČR GA305/00/1638 Institutional research plan: CEZ:AV0Z5011922 Keywords : hypertension * insulin sensitivity * passive membrane permeability Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.682, year: 2002

  10. New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

    Directory of Open Access Journals (Sweden)

    Kavita Venkataraman

    Full Text Available CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian, 21 to 40 years, body mass index 18-30 kg/m(2. Predicted ISI (ISI-cal was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ. In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD, using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR provided the best estimate of clamp-derived ISI (adjusted R(2 0.58 versus 0.32 HOMA-IR. In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05 for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001 for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and

  11. Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

    Science.gov (United States)

    Paniagua, Juan Antonio

    2016-01-01

    Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS. PMID

  12. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

  13. Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Juan; Antonio; Paniagua[1,2

    2016-01-01

    Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat.Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia,hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose.Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.

  14. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

  15. Limitations of insulin resistance assessment in polycystic ovary syndrome

    Science.gov (United States)

    Lewandowski, Krzysztof C; Płusajska, Justyna; Horzelski, Wojciech; Bieniek, Ewa; Lewiński, Andrzej

    2018-01-01

    Background Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. Subjects and methods In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). Results There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. Conclusions Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution. PMID:29436386

  16. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

    Science.gov (United States)

    Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

    2006-11-01

    The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

  17. Insulin resistance and serum parameters of iron status in type 2 diabetics

    International Nuclear Information System (INIS)

    Zafar, U.

    2011-01-01

    Background: Type 2 diabetes mellitus (T2DM) is a predominant public health concern worldwide, accounting for 90% of the cases of diabetes globally. Pathogenesis of T2DM involves insulin resistance, defective insulin secretion and increased glucose production by the liver. Subclinical haemochromatosis has been considered as one of the probable causes of insulin resistance and diabetes mellitus. The aim of this study was to determine and correlate insulin resistance and serum parameters of iron status (serum ferritin and transferrin saturation) in type 2 diabetics. Methods: It was a correlational study. This study was conducted on sixty male patients with type 2 diabetes mellitus. Fasting blood sample was taken from each subject and analysed for glucose, haemoglobin, insulin, iron, Total Iron Binding Capacity (TIBC) and ferritin. Insulin resistance was determined by HOMA-IR index. Transferrin saturation was calculated from serum iron and TIBC. Data was analysed using SPSS-17. Results: There was significant positive correlation between insulin resistance and transferrin saturation, but there was no significant correlation of insulin resistance with blood haemoglobin, serum iron and serum ferritin in type 2 diabetics. Conclusion: Correlation between insulin resistance and transferrin saturation reveals that iron has negative impact on insulin sensitivity in type 2 diabetics. (author)

  18. Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

    2013-01-01

    Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

  19. Fanconi anemia links reactive oxygen species to insulin resistance and obesity.

    Science.gov (United States)

    Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A; Rose, Susan R; Davies, Stella M; Pang, Qishen

    2012-10-15

    Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR.

  20. Mechanism by which arylamine N-acetyltransferase 1 ablation causes insulin resistance in mice

    DEFF Research Database (Denmark)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper

    2017-01-01

    A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we...... examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle...... adipose tissue, and hepatocytes. Taken together, these studies demonstrate that Nat1 deletion promotes reduced mitochondrial activity and is associated with ectopic lipid-induced insulin resistance. These results provide a potential genetic link among mitochondrial dysfunction with increased ectopic lipid...

  1. Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Padmanabhan, Vasantha

    2017-01-01

    Insulin resistance, a common feature of metabolic disorders such as obesity, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome, is a risk factor for development of diabetes. Because sex hormones orchestrate the establishment of sex-specific behavioral, reproductive, and metabolic differences, a role for them in the developmental origin of insulin resistance is also to be expected. Female sheep exposed to male levels of testosterone during fetal life serve as an excellent translational model for delineating programming of insulin resistance. This chapter summarizes the ontogeny of insulin resistance, the tissue-specific changes in insulin sensitivity, and the various factors that are involved in the programming and maintenance of the insulin resistance in adult female sheep that were developmentally exposed to fetal male levels of testosterone during the sexual-differentiation window.

  2. High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Li Zhi

    Full Text Available Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS production. Western blot analysis was used to examine the levels of insulin receptor (IR, phosphorylated insulin receptor substrate 1 (IRS1, Ser307 and phospho-Akt (Ser473. We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307 and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307 response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307 and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.

  3. Renal denervation for the management of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Patel HC

    2015-12-01

    Full Text Available Hitesh C Patel,1 Carl Hayward,1 Vassilis Vassiliou,1 Ketna Patel,2 James P Howard,3 Carlo Di Mario11NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK; 2Department of Cardiology, Royal Free Hospital, London, UK; 3National Heart and Lung Institute, Imperial College, London, UKAbstract: Renal sympathetic denervation (RSD as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP. However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their antihypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.Keywords: resistant hypertension, renal denervation, sympathetic nervous system

  4. Relationship among resistance to the insulin and obesity in Zacatecas population; Relacion entre resistencia a la insulina y obesidad en poblacion de Zacatecas

    Energy Technology Data Exchange (ETDEWEB)

    Zapata R, P G; Badillo A, V., E-mail: vbadillocren@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Ciencias Nucleares, Laboratorio de Radioinmunoanalisis y Quimioluminiscencia, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

    2012-10-15

    The Zacatecas State (Mexico) occupies the second national place in obesity, although the adults have a bigger incidence every time exist more minors that present this problem which can facilitate other illnesses like diabetes and hypertension. The first resistance references to the insulin were made by Himsworth in 1936, when he referred to insulin-resistant and insulin-sensitive diabetics. The resistance to the insulin, as event pathogen primary in the diabetes mellitus type 2 is derived of the obesity, what implies a subnormal biological response to the actions of the hormone in the carbohydrates, proteins and lipids metabolism. In this work was carried out a study of insulin levels for the Radioimmunoassay method in 40 patients with evident obesity and 8 patients with normal weight in order to evaluate these levels according to their age and abdominal circumference. Three correlations were made for both groups (obese and normal), the first correlation indicates the size of the waist with the insulin quantity, according to the arrangements that shows the correlation is bigger in all; what means that there is a great dependence among the size of the waist and the insulin quantity that contain. The second correlation is the age with the insulin that although is small, indicates that the age does not important for the insulin quantity that is secreted. The third and last realized correlation was of the age with the waist, and according to the results correlation also exists, but this is not significant as the first correlation. Therefore is considered existent the relationship between obesity and resistance to the insulin. (Author)

  5. Insulin resistance and cognitive performance in type 2 diabetes : The Maastricht study

    NARCIS (Netherlands)

    Geijselaers, Stefan L C; Sep, Simone J S; Schram, Miranda T; van Boxtel, Martin P J; Henry, Ronald M A; Verhey, Frans R J; Kroon, Abraham A; Schaper, Nicolaas C; Dagnelie, Pieter C; van der Kallen, Carla J H; Stehouwer, Coen D A; Biessels, Geert Jan

    AIMS: Type 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive

  6. Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?

    Directory of Open Access Journals (Sweden)

    Sofia Mikkelsen Berg

    2017-03-01

    Full Text Available Carnitine acetyltransferase (CRAT deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16 and octadecanoylcarnitine (C18 were slightly reduced in myotubes derived from T2DM patients (p<0.05 compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

  7. Periodontitis and Insulin Resistance: Casual or Causal Relationship?

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2012-12-01

    Full Text Available Insulin resistance (IR is now considered as a chronic and low level inflammatory condition. It is closely related to altered glucose tolerance, hypertriglyceridemia, abdominal obesity, and coronary heart disease. IR is accompanied by the increase in the levels of inflammatory cytokines like interleukin-1 and 6, tumor necrosis factor-α. These inflammatory cytokines also play a crucial part in pathogenesis and progression of insulin resistance. Periodontitis is the commonest of oral diseases, affecting tooth investing tissues. Pro-inflammatory cytokines are released in the disease process of periodontitis. Periodontitis can be attributed with exacerbation of IR. Data in the literature supports a "two way relationship" between diabetes and periodontitis. Periodontitis is asymptomatic in the initial stages of disease process and it often escapes diagnosis. This review presents the blurred nexus between periodontitis and IR, underlining the pathophysiology of the insidious link. The knowledge of the association between periodontitis and IR can be valuable in planning effectual treatment modalities for subjects with altered glucose homeostasis and diabetics. Presently, the studies supporting this association are miniscule. Further studies are mandatory to substantiate the role of periodontitis in the deterioration of IR.

  8. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.

    Science.gov (United States)

    Choi, Sun Ju; Kim, Francis; Schwartz, Michael W; Wisse, Brent E

    2010-06-01

    Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P fatty acid (100, 250, or 500 microM for neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

  9. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  10. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied....... In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia....... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  11. Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study.

    Directory of Open Access Journals (Sweden)

    Peyvand Amini

    Full Text Available Ghrelin is a 28-amino acid orexigenic peptide synthesized mainly in the stomach. Acute administration of ghrelin has been found to decrease insulin secretion. However, little data is available regarding whether ghrelin contributes to the long-term regulation of insulin resistance at the population level. The aim of this study is to investigate the association between circulating ghrelin and insulin resistance in a large population based study.A total of 2082 CODING study (Complex Diseases in the Newfoundland population: Environment and Genetics subjects were assessed. Subjects were of at least third generation Newfoundland descent, between the ages of 20 and 79 years, and had no serious metabolic, cardiovascular, or endocrine diseases. Ghrelin was measured with an Enzyme Immunoassay method. Insulin and fasting glucose were measured by Immulite 2500 autoanalyzer and Lx20 clinical chemistry analyzer, respectively. Homeostatic Model Assessment of β cell function (HOMA-β and Insulin Resistance (HOMA-IR and Quantitative Insulin-sensitivity Check Index (QUICKI were used for measurement of insulin resistance.Partial correlation analyses showed a significant negative correlation between circulating ghrelin and insulin level and insulin resistance in the entire cohort and also in men and women separately. The aforementioned correlation was independent of age, percentage of trunk fat and HDL-cholesterol. According to menopausal status, only pre-menopausal women revealed negative correlations.Our results suggest that except for postmenopausal women, high circulating ghrelin level is associated with lower insulin resistance in the general population.

  12. Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion.

    Science.gov (United States)

    Geffner, M E; Kaplan, S A; Bersch, N; Golde, D W; Landaw, E M; Chang, R J

    1986-03-01

    Six nonobese women with polycystic ovarian disease (PCOD) showed significant hyperinsulinemia, compared with controls after oral glucose (P less than 0.05). As an indicator of insulin sensitivity, in vitro proliferation of erythrocyte progenitor cells of PCOD subjects exposed to physiologic concentrations of insulin was significantly blunted (P less than 0.001). Monocyte insulin receptor binding was not impaired in the PCOD subjects. Three of the PCOD patients were treated with a long-acting gonadotropin-releasing hormone agonist for 6 months, which resulted in marked suppression of ovarian androgen secretion but no demonstrable changes in in vivo or in vitro indicators of insulin resistance. Thus insulin resistance in PCOD subjects appears to be unrelated to ovarian hyperandrogenism (or acanthosis or obesity). Although certain tissues are insulin-resistant in PCOD patients, the ovary may remain sensitive and overproduce androgens in response to high circulating insulin levels.

  13. Acute insulin resistance stimulates and insulin sensitization attenuates vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Cersosimo, Eugenio; Xu, Xiaojing; Upala, Sikarin; Triplitt, Curtis; Musi, Nicolas

    2014-08-01

    theory that differential regulation of insulin signaling pathways in VSMCs in insulin-resistant states plays an important role in inflammation, arterial wall thickening, and plaque formation during development of atherosclerosis. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Impact of Roux-en-Y Gastric Bypass on Metabolic Syndrome and Insulin Resistance Parameters

    Science.gov (United States)

    Gestic, Martinho Antonio; Utrini, Murillo Pimentel; Machado, Ricardo Rossetto; Geloneze, Bruno; Pareja, José Carlos; Chaim, Elinton Adami

    2014-01-01

    Abstract Background: Metabolic syndrome (MetS) is a complex association of clustering metabolic factors that increase risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Surgical treatment has become an important tool to achieve its control. The aim of this study was to evaluate the impact of Roux-en-Y gastric bypass (RYGB) on MetS and its individual components, clinical characteristics, and biochemical features. Subjects and Methods: The study is a retrospective cohort of 96 subjects with MetS who underwent RYGB and were evaluated at baseline and after surgery. Clinical and biochemical features were analyzed. Results: After surgery, significant rates of resolution for MetS (88.5%), T2DM (90.6%), hypertension (85.6%), and dyslipidemias (54.2%) were found. Significant decreases in levels of fasting glucose, fasting insulin, hemoglobin A1c, low-density lipoprotein, and triglycerides and an increase in high-density lipoprotein level were also shown. The decrease in insulin resistance evaluated by homeostasis model assessment (HOMA-IR) was consistent. MetS resolution was associated with postoperative glycemic control, decreases in levels of fasting glucose, hemoglobin A1c, HOMA-IR, and triglycerides and in antihypertensive usage, and percentage weight loss. Conclusions: This study found high rates of resolution for MetS, T2DM, hypertension, and dyslipidemias after RYGB in obese patients. This finding was consistent with current literature. Hence RYGB should be largely indicated for this group of subjects as it is a safe and powerful tool to achieve MetS control. PMID:24299427

  15. Catheter-Based Renal Denervation for Resistant Hypertension: Will It Ever Be Ready for "Prime Time"?

    Science.gov (United States)

    Laffin, Luke J; Bakris, George L

    2017-09-01

    The year 2014 was a turning point for the field of renal denervation (RDN) and its potential use to treat resistant hypertension. Tremendous enthusiasm shifted to sober reflection on the efficacy of a technology once touted as the cure to resistant hypertension. The following review highlights 2 major questions: First, does catheter-based RDN lower blood pressure and, second, will RDN using catheter-directed therapy for the treatment of resistant hypertension ever become more than an investigational technology. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Study on the inter-relationship among the changes of serum levels of leptin, insulin and glucagon in patients with DM2 complicated with hypertension

    International Nuclear Information System (INIS)

    Zeng Zhiwei; Yan Songqin; Tan Wei

    2006-01-01

    Objective: To investigate the inter-relationship among the changes of serum leptin, insulin and glucagon levels in patients with type 2 diabetes mellitus (DM2) complicated with hypertension. Methods: Serum leptin, insulin and glucagon levels were, measured with RIA in 30 DM2 patients complicated with hypertension, 30 DM2 patients without hypertension and 30 controls. Results: Serum levels of leptin, insulin and glucagon in all the DM2 patients were significantly higher than those in controls (P<0.01). In addition, the serum levels in DM2 patients with hypertension were significantly higher than those in DM2 patients without hypertension (P<0.05). These levels were positively correlated with the severity of hypertension. Conclusion: The role played by leptin and glucagon in the pathogenesis of type 2 diabetes mellitns should be furthur studied. (authors)

  17. Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

    International Nuclear Information System (INIS)

    Yousaf, I.; Hameed, W.; Rajput, T.A.

    2015-01-01

    Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

  18. Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus

    Science.gov (United States)

    Zhang, Yuehui; Sun, Xue; Sun, Xiaoyan; Meng, Fanci; Hu, Min; Li, Xin; Li, Wei; Wu, Xiao-Ke; Brännström, Mats; Shao, Ruijin; Billig, Håkan

    2016-01-01

    Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients. PMID:27461373

  19. Evaluation of insulin resistance in idiopathic hirsutism compared with polycystic ovary syndrome patients and healthy individuals.

    Science.gov (United States)

    Bonakdaran, Shokoufeh; Kiafar, Bita; Barazandeh Ahmadabadi, Fatemeh

    2016-02-01

    Hirsutism is defined as the excessive male-pattern growth of hair in women. Hirsutism is often idiopathic or the consequence of polycystic ovary syndrome (PCOS). Insulin resistance is common in PCOS (especially in obese patients) but the association between insulin resistance and idiopathic hirsutism (IH) is not clear. The aim of this study was to investigate the rate of insulin resistance in IH, compared with healthy individuals and patients with PCOS. The study included three groups, patients with idiopathic hirsutism, PCOS and healthy women. Each group included 30 non-obese women. Fasting blood sugar (FBS), insulin level and insulin resistance (estimated by the homeostasis model assessment [HOMA-IRIR]) were compared in the three groups. There was a significant difference between the age of the women with IH compared with two other groups. There were no significant difference in levels of serum insulin (P = 0.49, HOMA-IR (P = 0.47) and prevalence of insulin resistance (P = 0.07) in the three groups. The age-adjusted prevalence of insulin resistance was similar in the three groups. Insulin resistance was no more frequent in IH patients than in healthy control groups. © 2014 The Australasian College of Dermatologists.

  20. Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

    Science.gov (United States)

    Çakir, Evrim; Topaloğlu, Oya; Çolak Bozkurt, Nujen; Karbek Bayraktar, Başak; Güngüneş, Aşkın; Sayki Arslan, Müyesser; Öztürk Ünsal, İlknur; Tutal, Esra; Uçan, Bekir; Delıbaşi, Tuncay

    2014-01-01

    Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

  1. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  2. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    International Nuclear Information System (INIS)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-01-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

  3. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

    Science.gov (United States)

    Olmstead, Keedrian I.; La Frano, Michael R.; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A.; Newman, John W.; Fiehn, Oliver; Crocker, Daniel E.; Filipp, Fabian V.; Ortiz, Rudy M.

    2017-01-01

    Introduction Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. Objective To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. Methods We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. Results In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Conclusion Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. PMID:28757815

  4. Peroxisome Proliferator-Activated Receptors and Hepatitis C Virus-Induced Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Francesco Negro

    2009-01-01

    Full Text Available Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a, insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor γ. Whether and how this interaction may be manipulated pharmacologically, in order to improve the responsiveness to antivirals of insulin resistant chronic hepatitis C, patients remain to be fully explored.

  5. Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L

    2016-01-01

    computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose was measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR) with higher values indicating greater insulin resistance....... RESULTS: There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness and cortical thickness at the radius and tibia. These relationships remained even after adjusting for body weight and other potential...

  6. Definition, identification and treatment of resistant hypertension in chronic kidney disease patients.

    Science.gov (United States)

    Drexler, Yelena R; Bomback, Andrew S

    2014-07-01

    Resistant hypertension, the inability to achieve goal blood pressure despite the use of three or more appropriately dosed antihypertensive drugs (including a diuretic), remains a common clinical problem, especially in patients with chronic kidney disease (CKD). While the exact prevalence and prognosis of resistant hypertension in CKD patients remain unknown, resistant hypertension likely contributes significantly to increased cardiovascular risk and progression of kidney disease in this population. We review the identification and evaluation of patients with resistant hypertension, including the importance of 24-h ambulatory blood pressure monitoring in the identification of 'white-coat', 'masked' and 'non-dipper' hypertension, the latter of which has particular clinical and therapeutic importance in patients with resistant hypertension and CKD. We then discuss treatment strategies for resistant hypertension that target the pathophysiologic mechanisms underlying resistance to treatment, including persistent volume excess, incomplete renin-angiotensin-aldosterone system blockade and inadequate nocturnal blood pressure control. Finally, we propose a treatment algorithm for evaluation and treatment of resistant hypertension in patients with CKD. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  7. Renal denervation for the management of resistant hypertension

    Science.gov (United States)

    Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

    2015-01-01

    Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID:26672761

  8. Go-6976 Reverses Hyperglycemia-Induced Insulin Resistance Independently of cPKC Inhibition in Adipocytes

    Science.gov (United States)

    Robinson, Katherine A.; Hegyi, Krisztina; Hannun, Yusuf A.; Buse, Maria G.; Sethi, Jaswinder K.

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used “specific” inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not –β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

  9. Insulin resistance in type 1 diabetes: what is ?double diabetes? and what are the risks?

    OpenAIRE

    Cleland, S. J.; Fisher, B. M.; Colhoun, H. M.; Sattar, N.; Petrie, J. R.

    2013-01-01

    In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens ma...

  10. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    LENUS (Irish Health Repository)

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  11. Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study.

    Science.gov (United States)

    Lee, I-Te; Chiu, Yen-Feng; Hwu, Chii-Min; He, Chih-Tsueng; Chiang, Fu-Tien; Lin, Yu-Chun; Assimes, Themistocles; Curb, J David; Sheu, Wayne H-H

    2012-04-26

    Metabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families. Non-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components. Among the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16). In Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. ( NCT00260910, ClinicalTrials.gov).

  12. Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

    Science.gov (United States)

    Abbasi, Fahim; Okeke, QueenDenise; Reaven, Gerald M

    2014-04-01

    Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

  13. Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS

    DEFF Research Database (Denmark)

    Eriksen, Mette; Pørneki, Ann Dorte; Skov, Vibe

    2010-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating...

  14. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

    Science.gov (United States)

    Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

  15. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  16. Insulin resistance and risk of venous thromboembolism : results of a population-based cohort study

    NARCIS (Netherlands)

    Van Schouwenburg, I. M.; Mahmoodi, B. K.; Veeger, N. J. G. M.; Bakker, S. J. L.; Kluin-Nelemans, H. C.; Meijer, K.; Gansevoort, R. T.

    Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk

  17. Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia

    NARCIS (Netherlands)

    Visser, M. E.; Lammers, N. M.; Nederveen, A. J.; van der Graaf, M.; Heerschap, A.; Ackermans, M. T.; Sauerwein, H. P.; Stroes, E. S.; Serlie, M. J.

    2011-01-01

    Hepatic steatosis is strongly associated with hepatic and whole-body insulin resistance. It has proved difficult to determine whether hepatic steatosis itself is a direct cause of insulin resistance. In patients with familial hypobetalipoproteinaemia (FHBL), hepatic steatosis is a direct consequence

  18. Renal sympathetic denervation in the treatment of resistant hypertension.

    Science.gov (United States)

    Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

    2014-12-01

    Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17 mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.

  19. Exposures to arsenite and methylarsonite produce insulin resistance and impair insulin-dependent glycogen metabolism in hepatocytes.

    Science.gov (United States)

    Zhang, Chongben; Fennel, Emily M J; Douillet, Christelle; Stýblo, Miroslav

    2017-12-01

    Environmental exposure to inorganic arsenic (iAs) has been shown to disturb glucose homeostasis, leading to diabetes. Previous laboratory studies have suggested several mechanisms that may underlie the diabetogenic effects of iAs exposure, including (i) inhibition of insulin signaling (leading to insulin resistance) in glucose metabolizing peripheral tissues, (ii) inhibition of insulin secretion by pancreatic β cells, and (iii) dysregulation of the methylation or expression of genes involved in maintenance of glucose or insulin metabolism and function. Published studies have also shown that acute or chronic iAs exposures may result in depletion of hepatic glycogen stores. However, effects of iAs on pathways and mechanisms that regulate glycogen metabolism in the liver have never been studied. The present study examined glycogen metabolism in primary murine hepatocytes exposed in vitro to arsenite (iAs 3+ ) or its methylated metabolite, methylarsonite (MAs 3+ ). The results show that 4-h exposures to iAs 3+ and MAs 3+ at concentrations as low as 0.5 and 0.2 µM, respectively, decreased glycogen content in insulin-stimulated hepatocytes by inhibiting insulin-dependent activation of glycogen synthase (GS) and by inducing activity of glycogen phosphorylase (GP). Further investigation revealed that both iAs 3+ and MAs 3+ inhibit insulin-dependent phosphorylation of protein kinase B/Akt, one of the mechanisms involved in the regulation of GS and GP by insulin. Thus, inhibition of insulin signaling (i.e., insulin resistance) is likely responsible for the dysregulation of glycogen metabolism in hepatocytes exposed to iAs 3+ and MAs 3+ . This study provides novel information about the mechanisms by which iAs exposure impairs glucose homeostasis, pointing to hepatic metabolism of glycogen as one of the targets.

  20. Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Biagio Arcidiacono

    2012-01-01

    Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.