Higher Endogenous Glucose Production during OGTT vs Isoglycemic Intravenous Glucose Infusion

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Lund, Asger; Bagger, Jonatan I; Christensen, Mikkel Bring

2016-01-01

CONTEXT: Oral glucose ingestion elicits a larger insulin response and delayed suppression of glucagon compared to isoglycemic intravenous (iv) glucose infusion (IIGI). OBJECTIVE: We studied whether these differences translate into effects on endogenous glucose production (EGP) and glucose disposal......); HbA1c 53.8 ± 11.0 mmol/mol; duration of diabetes 9.2 ± 5.0 years) and 10 matched non-diabetic control subjects (age 56.0±10.7 years; BMI 29.8 ± 2.9 kg/m(2); HbA1c 33.8 ± 5.5 mmol/mol) Interventions: Three experimental days: 75 g-oral glucose tolerance test (OGTT), IIGI and IIGI+glucagon (IIGI...

Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration

NARCIS (Netherlands)

van Baak, M.A.; Mooij, J.M.

1994-01-01

Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration. Van Baak MA, Mooij JM. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. To investigate the effect of glucose (Glc) infusion on endurance performance after

[Influence of an infusion of 5- or 20% glucose solution on blood glucose and inorganic phosphate concentrations in dairy cows].

Science.gov (United States)

Aldaek, T A A; Failing, K; Wehrend, A; Klymiuk, M C

2011-01-01

The study was performed to evaluate the influence of an intravenous infusion of 5% and 20% dextrose solution on the plasma concentration of glucose and inorganic phosphate in healthy, dairy cows. Ten healthy, lactating, nonpregnant 3 to 6 year-old Holstein-Friesian cows were included in this investigation. The daily milk yield was 20.3±2.7 liters. Blood plasma concentrations of inorganic phosphate and glucose were determined before, during, immediately and 60 minutes after infusion of 0.9% physiological saline, 5% or 20% dextrose solution. A statistically significant influence of dextrose infusion on blood glucose concentration was observed. After 20% dextrose infusion (200 g dextrose) the blood glucose concentration increased by approximately 13.26 mmol/l. The administration of 5% dextrose solution (50 g dextrose) yielded an increase of blood glucose concentration by 3.31 mmol/l. There was no significant correlation between plasma inorganic phosphate concentrations and infusion of 0.9% saline, 5% or 20% dextrose solution. Intravenous administration of 1000 ml of 5% or 20% dextrose solution does not induce a lasting plasma phosphate reduction and is suitable for elevating the blood glucose concentration.

Direct vs. indirect pathway of hepatic glycogen synthesis as a function of glucose infusion rate

International Nuclear Information System (INIS)

Bagby, G.J.; Lang, C.H.; Johnson, J.L.; Blakesly, H.L.; Spitzer, J.J.

1986-01-01

This study was initiated to determine the influence of the rate of exogenous glucose administration on liver glycogen synthesis by the direct (glucose uptake and incorporation into glycogen) vs the indirect pathway (glucose degradation to 3-carbon intermediates, e.g., lactate, prior to incorporation into glycogen). Catheterized rats were fasted 2 days prior to receiving a 3 hr infusion of glucose at rates of 0 to 230 μmol/min/kg containing tracer [6- 3 H]- and [U- 14 C]-glucose. Plasma glucose (r = 0.80), insulin (r = 0.90) and lactate (r = 0.84) were correlated with glucose infusion rate. The rate of liver glycogen deposition (0.46 +/- 0.03 μmol/min/g) did not differ between a glucose infusion rate of 20 and 230 μmol/min/kg. At the lowest and highest glucose infusion rates hepatic glycogenesis accounted for 87 +/- 6 and 9 +/- 1% of the total glucose load, respectively. The percent contribution of the direct pathways to glycogen deposition ([ 3 H] specific activity in hepatic glycogen/[ 3 H] specific activity in plasma glucose) increased from 16 +/- 3 to 83 +/- 5% from lowest to highest glucose infusion rates (prevailing plasma glucose concentrations: 9 +/- 1 and 21 +/- 2 mM, respectively). The results indicate that the relative contribution of the direct and indirect pathways of glucogen synthesis are dependent upon the glucose load or plasma glucose concentration

Response to glucose and lipid infusions in sepsis: a kinetic analysis

International Nuclear Information System (INIS)

Shaw, J.H.; Wolfe, R.R.

1985-01-01

The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U- 14 C-glucose and 1,2, 13 C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of the control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

Science.gov (United States)

Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1987-01-01

Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 microU/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3- 3 H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 +/- 1% of basal (at 120-180 min) in the cold GINF studies, and 44 +/- 3 to 187 +/- 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 +/- 0.7 mg X min-1 X kg-1 at 25 min and remained significantly negative until 110 min (P less than .05). For the hot GINF studies, Ra was never significantly less than zero (P greater than .05) and was greater than in the cold GINF studies at 20-90 min (P less than .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal

Blood Glucose, Insulin and Inorganic Phosphorus in Healthy and Ketotic Dairy Cows after Intravenous Infusion of Glucose Solution

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Radojica Djoković

2009-01-01

Full Text Available The aim of the present study was to determine the degree of blood glucose utilization by peripheral tissue on the basis of changes in blood concentrations of glucose, insulin and inorganic phosphorus in healthy (n = 10 and ketotic cows (n = 10 after intravenous infusion of glucose solution. Blood samples were taken in both groups of examined cows at the following time intervals: just before (time 0 and 30, 60, 120, 180 and 240 min after intravenous infusion of a total of 500 ml of 50% of glucose solution. Glucose and insulin blood serum values in both groups of cows increased significantly within 30 and 60 min of the experiment (p p p < 0.05 in the blood value of inorganic phosphorus in ketotic cows compared to the healthy ones. This is linked with the active entry of glucose into the glucolytic pathway of peripheral tissues. It can thus be concluded that there is a higher degree of blood glucose utilization by peripheral tissues in ketotic cows.

Effect of glucose-insulin-potassium infusion on thallium myocardial clearance

International Nuclear Information System (INIS)

Wilson, R.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1983-01-01

Factors influencing the rate of 201 Tl clearance from the myocardium have not been clearly defined. This study determined the effect of an intravenous infusion of glucose-insulin-potassium (GIK) on the net 201 Tl clearance rates from myocardium with and without initial 201 Tl loading. Anesthetized open-chest dogs underwent 5 min of left anterior descending coronary artery occlusion and intravenous 201 Tl was injected and the occlusion released 5 min later. Thirty minutes after 201 Tl injection, 30 ml of either GIK (nine dogs) or saline (five dogs) was infused intravenously. The clearance rates of 201 Tl from the anterior wall (without initial 201 Tl loading) and from the posterior wall (with initial 201 Tl loading) were monitored with miniaturized cadmium telluride detectors placed on the myocardium. Calculation of net myocardial clearance rates was performed by linear regression analysis from serial 1 min counts. Compared with saline infusion, GIK increased the net clearance of 201 Tl from both myocardial regions with and without initial loading. The most marked change induced by GIK infusion was in the myocardial region without initial 201 Tl loading; a net increase in 201 Tl activity (72 +/- 42 cpm/30 min) was converted into a net loss (-594 +/- 228 cpm/30 min). There was no significant change in 201 Tl clearance after the saline infusion. Heart rate, aortic and left atrial pressure, sonomicrometer-measured transmural myocardial wall thickness, microsphere-determined myocardial blood flow, and blood glucose and potassium concentrations did not change significantly during GIK or saline infusions. Thus, GIK infusion appears to increase net 201 Tl clearance from myocardial zones with and without initial 201 Tl loading

Effect of intravenous glucose infusion on renal function in normal man and in insulin-dependent diabetics

DEFF Research Database (Denmark)

Frandsen, M; Parving, H H; Christiansen, JS

1981-01-01

The effect of intravenous glucose infusion on glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) and on urinary excretion of albumin and beta-2-microglobulin were studied in ten normal subjects and seven metabolically well......-controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7 +/- 0.1 to 10.9 +/- 0.4 mmol/l (SEM) (p less than or equal to 0.01). Glomerular filtration rate increased from 116 +/- 2 to 123 +/- 3 ml/mi x 1.73 m2 (p less than or equal to 0.01), while...... no change in renal plasma flow was seen - 552 +/- 11 versus 553 +/- 18 ml/min x 1.73 m2. Volume expansion with intravenous saline infusion in six of the normal subjects induced no changes in blood glucose or kidney function. In seven strictly controlled insulin-dependent diabetics, blood glucose values were...

Refractory hyperglycaemia induced by glucose-insulin-potassium infusion in acute myocardial infarction

NARCIS (Netherlands)

Svilaas, Tone; van der Horst, I.C.C.; Nijsten, M.W.N.; Zijlstra, F.

2006-01-01

Background. Recent randomised clinical trials have not confirmed the beneficial effects of glucose-insulin-potassium (GIK) infusion observed in experimental models of myocardial ischaemia and infarction. Methods. We investigated glucose levels and insulin dose in 107 patients treated with

Glucose and urea kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion, parenteral feeding, and surgical resection

International Nuclear Information System (INIS)

Shaw, J.H.; Wolfe, R.R.

1987-01-01

We isotopically determined rates of glucose turnover, urea turnover, and glucose oxidation in normal volunteers (n = 16), patients with early gastrointestinal (EGI) cancer (n = 6), and patients with advanced gastrointestinal (AGI) cancer (n = 10). Studies were performed in the basal state, during glucose infusion (4 mg/kg/min), and during total parenteral feeding (patients with AGI cancer only). Patients with early stages of the disease were also studied 2 to 3 months after resection of the cancer. Basal rates of glucose turnover were similar in volunteers and in patients with EGI cancer (13.9 +/- 0.3 mumol/kg/min and 13.3 +/- 0.2 mumol/kg/min, respectively) but were significantly higher in patients with AGI cancer (17.6 +/- 1.4 mumol/kg/min). Glucose infusion resulted in significantly less suppression of endogenous production in both patient groups than that seen in the volunteers (76% +/- 6% for EGI group, 69% +/- 7% for AGI group, and 94% +/- 4% for volunteers). The rate of glucose oxidation increased progressively in proportion to the tumor bulk. In the volunteers the percent of VCO2 from glucose oxidation was 23.9% +/- 0.7%, and in EGI and AGI groups the values were 32.8% +/- 2.0% and 43.0% +/- 3.0%, respectively. After curative resection of the cancer, glucose utilization decreased significantly (p less than 0.05). The rate of urea turnover was significantly higher in the AGI group (8.4 +/- 1.0 mumol/kg/min) in comparison with the volunteer group value of 5.9 +/- 0.6 mumol/kg/min (p less than 0.03). Glucose infusion resulted in a significant suppression of urea turnover in the volunteers (p less than 0.02), but in the AGI group glucose infusion did not induce a statistically significant decrease

Comparison of palmitic acid kinetics during glucose or ketone body infusions

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Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-03-05

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

Comparison of palmitic acid kinetics during glucose or ketone body infusions

International Nuclear Information System (INIS)

Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-01-01

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of [1- 14 C] palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat

The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

Science.gov (United States)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2016-08-01

Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

Effect of glucose and insulin infusion on the myocardial extraction of a radioiodinated methyl-substituted fatty acid

International Nuclear Information System (INIS)

Bianco, J.A.; Elmaleh, D.R.; Leppo, J.A.; King, M.A.; Moring, A.; Livni, E.; Espinoza, E.; Alpert, J.S.; Strauss, H.W.; Massachusetts General Hospital, Boston

1986-01-01

We investigated the one-way. An extraction of 14-iodophenyl-tetradecanoic acid (BMTDA) in the canine heart under fasting conditions and during infusion of glucose plus insulin in eight an esthetized greyhound dogs. Myocardial extraction measurements were made with dual tracer approach, using Tc-99m albumin as reference tracer. Prior to, and during, infusion of 10% glucose and 25 units of regular insulin, heart rate, blood pressure, plasma glucose, insulin and free fatty acid levels were measured. Myocardial blood flow was determined using Sn-113 and Ru-103 radioactive microspheres. The mean extraction fraction of BMTDA was 0.38+-SEM 0.06 at baseline and increased to 0.44+-0.06 during hyperglycemia plus insulin (P<0.025). Plasma glucose and insulin were higher during the infusion (P<0.01) while plasma free fatty acids significantly declined (P<0.01). There were no changes in hemodynamics or myocardial blood flow during the infusion. We conclude that glucose and insulin infusion result in increased first-pass extraction fraction of radioiodinated BMTDA unaccompanied by changes in coronary flow or hemodynamics, implying an insulin-mediated augmented transport of BMTDA. (orig.)

Experimental induction of abdominal tympany, abomasitis, and abomasal ulceration by intraruminal inoculation of Clostridium perfringens type A in neonatal calves.

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Roeder, B L; Chengappa, M M; Nagaraja, T G; Avery, T B; Kennedy, G A

1988-02-01

The etiologic role of Clostridum perfringens type A in the acute abdominal syndrome characterized by abomasal and rumen tympany, abomasitis, and abomasal ulceration was investigated in neonatal calves. Eight calves, 4 to 12 days old, were inoculated intraruminally with toxigenic C perfringens type A. Before and after C perfringens inoculation, blood samples were collected from all calves for blood gas and serum biochemical analysis and for determination of serum copper concentration; ruminal fluid was obtained for isolation of C perfringens. Calves were monitored daily for clinical signs of the syndrome and, depending on the severity of clinical signs, they were either euthanatized or redosed within 4 to 7 days. After necropsy, specimens obtained from the abomasum and rumen for macroscopic and microscopic examination and for anaerobic bacteriologic culture were processed in routine manner. Intraruminal inoculation of C perfringens type A into healthy calves induced anorexia, depression, bloat, diarrhea, and in some calves, death. Serum copper concentration was within normal range. Necropsy revealed variable degrees of abomasitis, petechial and ecchymotic hemorrhages, and ulcers (ranging from pinpoint to nearly perforate) in the abomasum. Seven of those calves also had multiple trichobezoars in the rumen. These necropsy findings were not seen in calves (controls) given distilled H2O only. In affected calves, acute abdominal syndrome was unrelated to copper deficiency, and C perfringens type A given intraruminally was able to induce clinical signs similar to those of the naturally acquired disease.

Changes in serum metabolic hormone levels after glucose infusion during lactation cycles in Holstein cows

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Aliasghar Chalmeh

2015-02-01

Full Text Available Negative energy balance can impair the metabolism of high producing dairy cows and supplying the glucose, as an energy source; can prevent the metabolic disorders in these animals. Hence, we hypothesized that bolus intravenous glucose administration may change the concentrations of metabolic hormones in order to prevent and control of metabolic dysfunctions of dairy cows. Twenty five multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactations, far-off and close-up dry periods. All cows were received dextrose 50% intravenously at 500 mg/kg, 10 mL/kg/h. Blood samples were collected from all animals prior to and 1, 2, 3 and 4 after dextrose 50% infusion and sera were separated to determine glucose, triiodothyronine (T3, thyroxine (T4, serum free T3 (fT3, free T4 (fT4, cortisol and insulin like growth factor-1 (IGF-1. The decreasing pattern of T3 concentration was detected in all studied animals following intravenous glucose infusion (P<0.05. The significant increasing pattern of T4 levels was seen in early and mid lactation cows after glucose administration (P<0.05. The significant decreasing pattern of IGF-1 was detected in mid and late lactations and far-off dry groups (P<0.05. There were no significant alterations in fT3, fT4 and cortisol concentrations following glucose infusion in all experimental groups. In conclusion, bolus intravenous glucose infusion could influence the metabolic hormones in high producing Holstein dairy cows. Alterations of metabolic hormones following bolus intravenous glucose administration indicated that glucose is an important direct controller of metabolic interactions and responses in dairy cows during different physiological states.

Effects of volatile fatty acid supply on their absorption and on water kinetics in the rumen of sheep sustained by intragastric infusions

NARCIS (Netherlands)

Lopez, S.; Hovell, F.D.D.; Dijkstra, J.; France, J.

2003-01-01

Three sheep fitted with a ruminal cannula and an abomasal catheter were used to study water kinetics and absorption of VFA infused continuously into the rumen. The effects of changing VFA concentrations in the rumen by shifting VFA infusion rates were investigated in an experiment with a 3 x 3 Latin

Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

DEFF Research Database (Denmark)

Nauck, Michael A; Walberg, Jörg; Vethacke, Arndt

2004-01-01

It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition.......It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition....

Effects of intravenous glucose infusion and nutritional balance on serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows.

Science.gov (United States)

Vieira, F V R; Lopes, C N; Cappellozza, B I; Scarpa, A B; Cooke, R F; Vasconcelos, J L M

2010-07-01

The objective of this study was to evaluate serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows according to nutritional balance and glucose infusion. Ten nonlactating, ovariectomized Gir x Holstein cows were stratified by body weight (BW) and body condition score (BCS) on d -28 of the study, and randomly assigned to 1) negative nutrient balance (NB) or 2) positive nutrient balance (PB). From d -28 to d 0, cows were allocated according to nutritional treatment (5 cows/treatment) into 2 low-quality pastures with reduced forage availability. However, PB cows individually received, on average, 3 kg/cow per day (as-fed) of a concentrate during the study. All cows had an intravaginal progesterone releasing device inserted on d -14, which remained in cows until the end of the study. Cow BW and BCS were assessed again on d 0. On d 0, cows within nutritional treatment were randomly assigned to receive, in a crossover design containing 2 periods of 24h each, 1) intravenous glucose infusion (GLU; 0.5 g of glucose/kg of BW, as a 5% glucose solution administered, on average, at 32 mL/min over a 3-h period), or 2) intravenous saline infusion (SAL; 0.9% solution infused on average at 32 mL/min over a 3-h period). Prior to the beginning of each period, all cows were fasted for 12h. Blood samples were collected, relative to the beginning of the infusion, at -12 and -11.5h (beginning of fasting), and at -0.5, 0, 0.5, 1, 2, 3, 4, 5, and 6h. Following the last blood collection of period 1, cows received (PB) or not (NB) concentrate and were returned to their respective pastures. Changes in BCS and BW were greater in NB cows compared with PB cows (-0.60 and -0.25+/-0.090 for BCS, respectively; -22.4 and 1.2+/-6.58 kg for BW, respectively). Cows receiving GLUC had greater glucose concentrations from 0.5 to 3h relative to infusion compared with SAL cows. Insulin concentrations were greater in PB cows assigned to GLUC compared

Effect of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin-conjugating enzyme gene expression in calves

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Scaife Jes R

2008-02-01

Full Text Available Abstract Background Intravenous infusions of glucose and amino acids increase both nitrogen balance and muscle accretion. We hypothesised that co-infusion of glucose (to stimulate insulin and essential amino acids (EAA would act additively to improve nitrogen balance by decreasing muscle protein degradation in association with alterations in muscle expression of components of the ubiquitin-proteasome proteolytic pathway. Methods We examined the effect of a 5 day intravenous infusions of saline, glucose, EAA and glucose + EAA, on urinary nitrogen excretion and muscle protein degradation. We carried out the study in 6 restrained calves since ruminants offer the advantage that muscle protein degradation can be assessed by excretion of 3 methyl-histidine and multiple muscle biopsies can be taken from the same animal. On the final day of infusion blood samples were taken for hormone and metabolite measurement and muscle biopsies for expression of ubiquitin, the 14-kDa E2 ubiquitin conjugating enzyme, and proteasome sub-units C2 and C8. Results On day 5 of glucose infusion, plasma glucose, insulin and IGF-1 concentrations were increased while urea nitrogen excretion and myofibrillar protein degradation was decreased. Co-infusion of glucose + EAA prevented the loss of urinary nitrogen observed with EAA infusions alone and enhanced the increase in plasma IGF-1 concentration but there was no synergistic effect of glucose + EAA on the decrease in myofibrillar protein degradation. Muscle mRNA expression of the ubiquitin conjugating enzyme, 14-kDa E2 and proteasome sub-unit C2 were significantly decreased, after glucose but not amino acid infusions, and there was no further response to the combined infusions of glucose + EAA. Conclusion Prolonged glucose infusion decreases myofibrillar protein degradation, prevents the excretion of infused EAA, and acts additively with EAA to increase plasma IGF-1 and improve net nitrogen balance. There was no evidence of

Operant licking for intragastric sugar infusions: differential reinforcing actions of glucose, sucrose and fructose in mice

Science.gov (United States)

Sclafani, Anthony; Ackroff, Karen

2015-01-01

Intragastric (IG) flavor conditioning studies in rodents indicate that isocaloric sugar infusions differ in their reinforcing actions, with glucose and sucrose more potent than fructose. Here we determined if the sugars also differ in their ability to maintain operant self-administration by licking an empty spout for IG infusions. Food-restricted C57BL/6J mice were trained 1 h/day to lick a food-baited spout, which triggered IG infusions of 16% sucrose. In testing, the mice licked an empty spout, which triggered IG infusions of different sugars. Mice shifted from sucrose to 16% glucose increased dry licking, whereas mice shifted to 16% fructose rapidly reduced licking to low levels. Other mice shifted from sucrose to IG water reduced licking more slowly but reached the same low levels. Thus IG fructose, like water, is not reinforcing to hungry mice. The more rapid decline in licking induced by fructose may be due to the sugar's satiating effects. Further tests revealed that the Glucose mice increased their dry licking when shifted from 16% to 8% glucose, and reduced their dry licking when shifted to 32% glucose. This may reflect caloric regulation and/or differences in satiation. The Glucose mice did not maintain caloric intake when tested with different sugars. They self-infused less sugar when shifted from 16% glucose to 16% sucrose, and even more so when shifted to 16% fructose. Reduced sucrose self-administration may occur because the fructose component of the disaccharide reduces its reinforcing potency. FVB mice also reduced operant licking when tested with 16% fructose, yet learned to prefer a flavor paired with IG fructose. These data indicate that sugars differ substantially in their ability to support IG self-administration and flavor preference learning. The same post-oral reinforcement process appears to mediate operant licking and flavor learning, although flavor learning provides a more sensitive measure of sugar reinforcement. PMID:26485294

Glucose tracer, kinetics and turnover in monkeys and chickens infused with ethanol, 1,3-butanediol, or fructose

International Nuclear Information System (INIS)

Armstrong, M.K.

1985-01-01

Mixtures of (2- 3 H) and (U- 14 C) glucose were injected as single doses into fasted cynomolgus monkeys to assess glucose tracer kinetics and obtain rates of turnover. Data were treated by stochastic and compartmental analyses and results from both analyses closely agreed. However, (2- 3 H) data analyzed by the compartmental analysis required three pools to fit the glucose disappearance curve while (6- 3 H) data fit a two or three pool model equally well. Turnover rates averaged 4.9-4.0, and 3.0 mg/min x kg -1 body weight with (2- 3 H), 6- 3 H) and (U- 14 C) glucose tracers, respectively. The data heuristically suggest that the slow turnover pool that was necessary to fit (2- 3 H) glucose data is related to isotope discrimination. The effects of four treatment solutions on (6- 3 H) glucose metabolism in monkeys were examined. The solutions and their rates of infusion (umoles/min x kg -1 ) were: (1) ethanol, 110; (2) 1,3-butanediol, 110; (3) fructose, 30; and (4) ethanol pus fructose, 110 and 30, respectively. The glucose clearance rate was lowest during the ethanol plus fructose infusions. Ethanol infusions (222 or 444 umoles/min x kg -1 body weight) in chickens (1500 g) fasted 64 hours did not cause hypoglycemia although the high dose slightly decreased the rate of glucose turnover 15% (14.0 versus 12.0 mg/min x kg -1 ). It was further found that neither the hepatic cytosolic nor the mitochondrial redox state significantly changed in chickens infused with the high dose of ethanol. The unchanged hepatic metabolite ratios in chickens are consistent with their unusual resistance to ethanol-induced hypoglycemia

Glucose and protein kinetics in patients undergoing colorectal surgery: perioperative amino acid versus hypocaloric dextrose infusion.

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Lugli, Andrea Kopp; Schricker, Thomas; Wykes, Linda; Lattermann, Ralph; Carli, Franco

2010-11-01

Surgical injury provokes a stress response that leads to a catabolic state and, when prolonged, interferes with the postoperative recovery process. This study tests the impact of 2 nutrition support regimens on protein and glucose metabolism as part of an integrated approach in the perioperative period incorporating epidural analgesia in 18 nondiabetic patients undergoing colorectal surgery. To test the hypothesis that parenteral amino acid infusion (amino acid group, n = 9) maintains glucose homeostasis while maintaining normoglycemia and reduces proteolysis compared with infusion of dextrose alone (DEX group, n = 9), glucose and protein kinetics were measured before and on the second day after surgery using a stable isotope tracer technique. Postoperatively, the rate of appearance of glucose was higher (P dextrose alone. Copyright © 2010 Elsevier Inc. All rights reserved.

Responses of Blood Glucose, Insulin, Glucagon, and Fatty Acids to Intraruminal Infusion of Propionate in Hanwoo

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Y. K. Oh

2015-02-01

Full Text Available This study was carried out to investigate the effects of intraruminal infusion of propionate on ruminal fermentation characteristics and blood hormones and metabolites in Hanwoo (Korean cattle steers. Four Hanwoo steers (average body wt. 270 kg, 13 month of age equipped with rumen cannula were infused into rumens with 0.0 M (Water, C, 0.5 M (37 g/L, T1, 1.0 M (74 g/L, T2 and 1.5 M (111 g/L, T3 of propionate for 1 hour per day and allotted by 4×4 Latin square design. On the 5th day of infusion, samples of rumen and blood were collected at 0, 60, 120, 180, and 300 min after intraruminal infusion of propionate. The concentrations of serum glucose and plasma glucagon were not affected (p>0.05 by intraruminal infusion of propionate. The serum insulin concentration at 60 min after infusion was significantly (p<0.05 higher in T3 than in C, while the concentration of non-esterified fatty acid (NEFA at 60 and 180 min after infusion was significantly (p<0.05 lower in the propionate treatments than in C. Hence, intraruminal infusion of propionate stimulates the secretion of insulin, and decreases serum NEFA concentration rather than the change of serum glucose concentration.

Dextrose infusion and glucose disorders in people without diabetes hospitalized in general wards.

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Feldman-Billard, Sylvie; Joubert, Michael; Reznik, Yves

2013-11-01

We measured fasting plasma glucose (FPG) on a single day in all persons without diabetes history admitted in general wards (N=1922). After age and length of stay adjustment, dextrose infusion was associated with a 3-fold increase (p<0.001) of hospital-related hyperglycemia (FPG ≥ 7 mmol/l), highlighting the need to interpret glucose disorders cautiously. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men.

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Schultes, Bernd; Panknin, Ann-Kristin; Hallschmid, Manfred; Jauch-Chara, Kamila; Wilms, Britta; de Courbière, Felix; Lehnert, Hendrik; Schmid, Sebastian M

2016-10-01

Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 ± 0.8 vs. 5.3 ± 0.3 mmol/l; t(14) = -5.159, p hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum concentrations of haptoglobin and serum amyloid A in water buffaloes (Bubalus bubalis with abomasal ulcer

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Javad Tajik

2012-09-01

Full Text Available To evaluate the serum concentrations of haptoglobin (Hp and serum amyloid A (SAA in water buffaloes with abomasal ulcers, the abomasums of 100 randomly selected water buffaloes were examined after slaughter. Type I abomasal ulcers were found in 56 out of 100 buffaloes. Serum concentrations of Hp and SAA were measured. There was no significant difference between affected and non-affected buffaloes in the serum concentrations of Hp and SAA. The serum concentrations of Hp and SAA had no significant correlation with age and the serum SAA revealed no significant correlation with the number of abomasal ulcers. A significant correlation was found between the serum Hp and the number of abomasal ulcers (r =0.29, p = 0.04. There was no significant difference in the serum concentrations of Hp and SAA between buffaloes with different ulcer locations in the abomasums. Although more work on a larger number of animals is required in this area, it seems that the measurement of the serum Hp can be used to predict the abundance of type I abomasal ulcers.

Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.

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Curtis, Richelle V; Kim, Julie J M; Doelman, John; Cant, John P

2018-05-01

The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of milk protein yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments. Compared with saline, glucose infusion did not affect dry matter intake but increased milk yield by 2.2 kg/d and milk protein and lactose yields by 63 and 151 g/d, respectively. Mammary plasma flow increased 36% during glucose infusion compared with saline infusion, possibly because of a 31% decrease in total acetate plus β-hydroxybutyrate concentrations. Circulating concentrations of total essential AA and BCAA decreased 19 and 31%, respectively, during infusion of glucose, yet net mammary uptakes of AA remained unchanged compared with saline infusion. The addition of 75 and 150 g/d of BCAA to glucose infusions increased arterial concentrations of BCAA to 106 and 149%, respectively, of the concentrations in saline-infused cows, but caused a decrease in concentrations of non-branched-chain essential AA in plasma, as well as their mammary uptakes and milk protein yields. Plasma urea concentration was not affected by BCAA infusion, indicating no change in catabolism of AA. The lack of mammary and catabolic effects leads us to suggest that BCAA exerted their effects on plasma concentrations of the other essential AA by stimulating utilization in skeletal muscle for protein accretion. Results indicate that the glucose effect on milk protein yield was not limited by low BCAA concentrations, and that a stimulation of extra-mammary use

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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Stengärde Lena

2008-08-01

Full Text Available Abstract Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations. Cows were examined and blood sampled every three weeks from four weeks ante partum (ap to nine weeks postpartum (pp. Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA, insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

2008-01-01

Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females

DEFF Research Database (Denmark)

Becker, U; Gluud, C; Bennett, Patrick

1988-01-01

after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments...... and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione...

Diagnosing impaired glucose tolerance using direct infusion mass spectrometry of blood plasma.

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Petr G Lokhov

Full Text Available The goal of this study was to evaluate the capacity for mass spectrometry of blood plasma to diagnose impaired glucose tolerance (IGT. For this study, blood plasma samples from control subjects (n = 30 and patients with IGT (n = 20 were treated with methanol and low molecular weight fraction were then analyzed by direct infusion mass spectrometry. A total of 51 metabolite ions strongly associated with IGT were detected. The area under a receiver operating characteristic (ROC curve (AUC for diagnosing IGT that was based on an analysis of all these metabolites was 0.93 (accuracy 90%, specificity 90%, and sensitivity 90%. The associated reproducibility was 85%. The metabolites identified were also consistent with risk factors previously associated with the development of diabetes. Thus, direct infusion mass spectrometry of blood plasma metabolites represents a rapid, single-step, and reproducible method for the analysis of metabolites. Moreover, this method has the potential to serve as a prototype for clinical analyses that could replace the currently used glucose tolerance test with a more patient-friendly assay.

Body Temperatures During Exercise in Deconditioned Dogs: Effect of NACL and Glucose Infusion

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Greenleaf, J. E.; Kruk, B.; Nazar, K.; Kaciuba-Usciko, H.

2000-01-01

Infusion of glucose (Glu) into normal exercising dogs attenuates the rise in rectal temperature (Delta-Tre) when compared with delta-Tre during FFA infusion or no infusion. Rates of rise and delta-=Tre levels are higher during exercise after confinement. Therefore, the purpose of this study was to determine if Glu infusion would attenuate the exercise-induced excess hyperthermia after deconditioning. Rectal and quadricep femoris muscle temperatures (Tmu) were measured in 7 male, mongrel dogs dogs (19.6 +/- SD 3.0 kg) during 90 minutes of treadmill exercise (3.1 +/-SD 0.2 W/kg) with infusion (30ml/min/kg) of 40% Glu or 0.9% NaCL before BC) and after confinement (AC) in cages (40 x 110 x 80 cm) for 8 wk. Mean (+/-SE body wt. were 19.6 +/- 1.1 kg BC and 19.5 +/- 1.1kg AC, exercise VO2 were not different (40.0 - 42.0 mi/min/kg-1). With NaCl AC, NaCl BC, GluAC, and GluBC: Delta-Tre were, 1.8, 1.4, 1.3 and 0.9C respectively; and Delta-Tmu were 2.3, 1.9, 1.6, and 1.4C. respectively (Pbody temperature with Glu infusion must affect avenues of heat dissipation.

Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

DEFF Research Database (Denmark)

Falkén, Y; Hellström, P M; Sanger, G J

2010-01-01

Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis...... during a 6-h infusion in humans....

Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

DEFF Research Database (Denmark)

Kølendorf, K; Christiansen, J S; Bojsen, J

1981-01-01

UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...

Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

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Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

2003-01-01

not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.......We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...

Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.

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Poppitt, Sally D; Shin, Hyun Sang; McGill, Anne-Thea; Budgett, Stephanie C; Lo, Kim; Pahl, Malcolm; Duxfield, Janice; Lane, Mark; Ingram, John R

2017-09-01

Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies. Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides. Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner. Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853. © 2017 American Society for Nutrition.

Effect of Insulin Infusion on Liver Protein Synthesis during Hemodialysis

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Reinhard, Mark; Frystyk, Jan; Jespersen, Bente

2011-01-01

Background Hemodialysis (HD) is a catabolic procedure that may contribute to the high frequency of protein-energy wasting among patients receiving maintenance HD. The present study investigated the additional effect of glucose and glucose-insulin infusion on liver protein synthesis during HD...... compared with a meal alone. Methods In a randomized cross-over study with three arms, 11 non-diabetic HD patients were assigned to receive a conventional HD session with either: • no treatment (NT) • IV infusion of glucose (G) • IV infusion of glucose-insulin (GI) During infusions blood glucose levels were...... maintained at 8.0-10.0 mmol/L by additional glucose infusion. Glucose and glucose-insulin infusions were commenced 2 h prior to HD and continued throughout the HD session. Fasting blood samples were collected at baseline before infusion and followed by the only meal allowed during the study. Results Blood...

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

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Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

1999-01-01

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefo....... CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.......OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...

Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

International Nuclear Information System (INIS)

Levy, J.C.; Brown, G.; Matthews, D.R.; Turner, R.C.

1989-01-01

Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively)

Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels

OpenAIRE

Krebs-Kraft, Desiree L.; Rauw, Gail; Baker, Glen B.; Parent, Marise B.

2009-01-01

Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated. For instance, hippocampal glucose infusions reverse the memory-impairing effects of co-infusions of the GABA agonist muscimol, whereas septal glucose infusions exacerbate memory deficits produced by muscimol. One potential explanation for these deleterious effects of glucose in the septum is that there are highe...

Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Knop, F K; Vilsbøll, T; Madsbad, S

2007-01-01

AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes. MATERIALS AND METHODS: Ten patients (eight men) with type 2 diabetes (age: 64...... during the 2 days was obtained in both groups. In the control subjects no difference in glucagon suppression during the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (-36 +/- 12 vs -64 +/- 23 mmol/l x 45 min; p = NS) was observed, whereas in the group of patients with type 2 diabetes...... significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion...

Underestimation of glucose turnover corrected with high-performance liquid chromatography purification of [6-3H]glucose

International Nuclear Information System (INIS)

Schwenk, W.F.; Butler, P.C.; Haymond, M.W.; Rizza, R.A.

1990-01-01

We have recently reported that during infusion of commercially available [6-3H]glucose, a radioactive nonglucose contaminant may accumulate in plasma causing errors in the measurement of glucose turnover. To determine whether purification of this tracer by HPLC (high-performance liquid chromatography) before infusion would eliminate the contaminant in plasma and remove the underestimation of glucose turnover reported during hyperinsulinemia, four normal subjects each underwent two 5-h euglycemic clamps during infusion of insulin (1 mU.kg-1.min-1). Glucose turnover was measured with either commercially available [6-3H]glucose or with HPLC-purified [6-3H]glucose. HPLC analysis of samples from the clamps done with commercially available [6-3H]glucose showed that 9.7% of the infused tracer and 26% of the plasma glucose 3H radioactivity were contaminants. In contrast, no contaminant was observed in the plasma during infusion of HPLC-purified [6-3H]glucose. During the last hour of the clamp, mean glucose turnover using commercially available [6-3H]glucose was less (P less than 0.01) than the mean glucose infusion rate (7.6 +/- 0.3 vs. 10.5 +/- 0.3 mg.kg-1.min-1) yielding apparent negative (P less than 0.001) hepatic glucose release. In contrast, when HPLC-purified [6-3H]glucose was employed, glucose turnover equaled the glucose infusion rate (10.4 +/- 0.9 vs. 10.2 +/- 0.9 mg.kg-1.min-1) and hepatic glucose release was no longer negative. We conclude that removal of a tritiated nonglucose contaminant in [6-3H]glucose by HPLC yields correct estimations of glucose turnover at steady state

Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.

Science.gov (United States)

Maury, Eric; Vitry, Paola; Galbois, Arnauld; Ait-Oufella, Hafid; Baudel, Jean-Luc; Guidet, Bertrand; Offenstadt, Georges

2012-06-14

We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

Pathomorphological characteristics of abomasal ulcers in high-yielding dairy cows

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Kureljušić Branislav

2013-01-01

Full Text Available The aim of this paper was to investigate the morphology, localization and typization of abomasal ulcers in high-yielding dairy cows, as a contribution to the existing knowledge on the subject. A total of ten high-yielding dairy cows which died during the period of early puerperium and two Holstein heifers which died in late pregnancy after transport to a new location were investigated in this study. Samples of altered abomasal tissue were taken at necropsy for further histopathology and mycology investigations. The disclosed ulcerations of the abomasums in twelve investigated animals differed among them not only as far as localization and morphology are concerned, but also in the degree of intramural penetration. Such differences distinguished them into four types. Ulcerations of type one and type two, recorded in two heifers and six cows, as well as in one cow with lymphoma of the abomasum. Perforating ulcer of type three, with circumscripted peritonitis was diagnosed in one cow in the corpus of the abomasum close to the curvatura major. An interesting finding was the simultaneous occurrence of type four perforating ulcer and ulcer-type one, which were located next to each other. Histopathological examination of the structure of the ulcerated abomasum dyed with the hematoxylin-eosin method showed that coagulation necrosis in the area of the ulceration revealed a moderate inflammatory infiltrate in the lamina propria. In the cow affected with lymphoma, a copious tumorous lymphoid infiltrate was concurrent. Mycotic ulcerative abomasitis was described in a cow seven days after calving. In these lesions Aspergillus fumigatus and Mucor spp. were isolated. Histopathological analysis of tissue samples dyed with the Grocott method, described septed and nonsepted hyphae in the blood vessels and surrounding tissue of the tunica mucosa and submucosa.

Changes in Blood Values of Glucose, Insulin and Inorganic Phosphorus in Healthy and Ketotic Dairy Cows after Intravenous Infusion of Propionate Solution

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R. Djoković

2007-01-01

Full Text Available The aim of the present study was to determine the degree of blood glucose utilization by peripheral tissue on the basis of changes in blood concentrations of glucose, insulin and inorganic phosphorus in healthy (n = 10 and ketotic cows (n = 10 after intravenous infusion of propionate solution. Blood samples were taken in both groups of examined cows at the following time intervals: just before (time 0 and 8, 30, 60, 120, 180, 240 and 480 min after the intravenous infusion of 1.84 mol l-1 solution of propionate in the amount of 1 ml kg-1 of body weight. Glucose and insulin blood serum values in both groups of cows increased significantly within 120 min of the experiment (p p p p < 0.05 in blood value of inorganic phosphorus in ketotic cows in comparison with healthy ones. This is linked with the active entry of glucose into glucolytic pathway of peripheral tissues. It can thus be concluded that there is a higher degree of blood glucose utilization by peripheral tissues in ketotic cows.

Autophagy in muscle of glucose-infusion hyperglycemia rats and streptozotocin-induced hyperglycemia rats via selective activation of m-TOR or FoxO3.

Directory of Open Access Journals (Sweden)

Pengfei Lv

Full Text Available Autophagy is a conserved process in eukaryotes required for metabolism and is involved in diverse diseases. To investigate autophagy in skeletal muscle under hyperglycemia status, we established two hyperglycemia-rat models that differ in their circulating insulin levels, by glucose infusion and singe high-dose streptozotocin injection. We then detected expression of autophagy related genes with real-time PCR and western blot. We found that under hyperglycemia status induced by glucose-infusion, autophagy was inhibited in rat skeletal muscle, whereas under streptozotocin-induced hyperglycemia status autophagy was enhanced. Meanwhile, hyperglycemic gastrocnemius muscle was more prone to autophagy than soleus muscle. Furthermore, inhibition of autophagy in skeletal muscle in glucose-infusion hyperglycemia rats was mediated by the m-TOR pathway while m-TOR and FoxO3 both contributed to enhancement of autophagy in gastrocnemius muscle in streptozotocin-induced hyperglycemia rats. These data shows that insulin plays a relatively more important role than hyperglycemia in regulating autophagy in hyperglycemia rat muscle through selectively activating the m-TOR or FoxO3 pathway in a fiber-selective manner.

Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion

International Nuclear Information System (INIS)

Wolfe, R.R.; Shaw, J.H.; Durkot, M.J.

1985-01-01

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2- 3 H]glycerol and [1- 14 C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1- 13 C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. The authors conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis

Glucose and insulin dynamics associated with continuous rate infusion of dextrose solution or dextrose solution and insulin in healthy and endotoxin-exposed horses.

Science.gov (United States)

Han, Janet H; McKenzie, Harold C; McCutcheon, L Jill; Geor, Raymond J

2011-04-01

To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses. 9 adult mares. During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (group 2; n = 4) or horses administered 35 ng of lipopolysaccharide/kg, IV, 24 hours before starting the dextrose solution and insulin CRIs (group 3; 4). A balanced crossover study design was used in both phases. Blood samples were collected for measurement of plasma glucose and insulin concentrations. Infusion of dextrose solution alone resulted in hyperglycemia for most of the 360-minute CRI. Insulin concentration increased significantly in group 1, compared with that in the control group. Mean insulin concentration of group 2 was significantly higher throughout most of the infusion period, compared with concentrations of the control group and group 1. Mean glucose concentration did not differ significantly between groups 2 and 3. Insulin infusion at a rate of 0.07 U/kg/h was found to be effective for the prevention of hyperglycemia when administered concurrently with dextrose solution. This rate was considered to be safe because horses did not become hypoglycemic during infusions of dextrose solution.

Acute effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate responses to intraduodenal glucose infusion in type 2 diabetes.

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Thazhath, Sony S; Marathe, Chinmay S; Wu, Tongzhi; Chang, Jessica; Khoo, Joan; Kuo, Paul; Checklin, Helen L; Bound, Michelle J; Rigda, Rachael S; Horowitz, Michael; Jones, Karen L; Rayner, Christopher K

2017-01-01

To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes. Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min -1 ) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and amplitude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales. During intraduodenal glucose infusion (0-60 min), diastolic (p (0-60)  = 0.03) and mean arterial (p (0-60)  = 0.03) blood pressures and heart rate (p (0-60)  = 0.06; p (0-120)  = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control (p = 0.007 and 0.04, respectively). In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension. © The Author(s) 2016.

Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

DEFF Research Database (Denmark)

Kloster, Brian O; Lund, Lars; Lindholt, Jes S

2016-01-01

to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. METHODS: The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten...... of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. RESULTS: All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned...... and histology. CONCLUSION: In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human...

Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans

DEFF Research Database (Denmark)

Steensberg, Adam; Fischer, Christian P; Sacchetti, Massimo

2003-01-01

adrenaline (epinephrine). IL-6 infusion, irrespective of dose, did not result in any changes to endogenous glucose production, whole-body glucose disposal or leg- glucose uptake. These data demonstrate that acute IL-6 administration does not impair whole-body glucose disposal, net leg-glucose uptake......The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of three...... the cessation of infusion (recovery) to determine endogenous glucose production and whole-body glucose disposal. Infusion with HiIL-6 and LoIL-6 resulted in a marked (P

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

International Nuclear Information System (INIS)

Paolisso, G.; Scheen, A.J.; Luyckx, A.S.; Lefebvre, P.J.

1987-01-01

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin, basal insulin secretion was replaced by a continuous insulin infusion, and glucagon was infused intravenously in two conditions at random: either continuously or intermittently. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3- 3 H]glucose infusion allowed the authors to study glucose turnover. While basal plasma glucagon levels were similar in both conditions, they plateaued at 189 +/- 38 pg ml -1 during continuous infusion and varied between 95 and 501 pg x ml -1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion 1) initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, 2) did not prevent the so-called evanescent effect of glucagon on blood glucose, and 3) after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucanemia in normal man fails to increase hepatic glucose production

Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

International Nuclear Information System (INIS)

Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S.

1990-01-01

We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP

Effect of grape seed extract, Cistus ladanifer L., and vegetable oil supplementation on fatty acid composition of abomasal digesta and intramuscular fat of lambs.

Science.gov (United States)

Jerónimo, Eliana; Alves, Susana P; Dentinho, Maria T P; Martins, Susana V; Prates, José A M; Vasta, Valentina; Santos-Silva, José; Bessa, Rui J B

2010-10-13

Thirty-six lambs were used in a 6 week experiment to evaluate the effect of vegetable oil blend supplementation (0 vs 60 g/kg of dry matter (DM)) and two dietary condensed tannin sources, grape seed extract (0 vs 25 g/kg of DM) and Cistus ladanifer L. (0 vs 250 g/kg of DM), on fatty acid (FA) composition of abomasal digesta and intramuscular polar and neutral lipids. Grape seed extract did not affect the FA profile of abomasal digesta or muscle lipid fractions. C. ladanifer had a minor effect in lambs fed diets with no oil but greatly changed the abomasal and muscle FA profiles in oil-supplemented lambs. It decreased 18:0 and increased 18:1 trans-11 in abomasal digesta and increased 18:1 trans-11 and 18:2 cis-9,trans-11 (P = 0.062) in muscle neutral lipids, resulting in an important enrichment of meat 18:2 cis-9,trans-11 when compared to other oil-supplemented diets (19.2 vs 41.7 mg/100 g of muscle).

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

International Nuclear Information System (INIS)

Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

1986-01-01

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6- 3 H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 μU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production

Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient

Science.gov (United States)

Gerber, Bryan; Kenyon, Katharine; Muthukanagaraj, Purushothaman

2017-01-01

Vitamin C supplementation is generally regarded as benign. There has been a resurgence of interest in the general medical community regarding the use of vitamin C most notably in the care of sepsis. Nonetheless, caution must be taken if supraphysiologic vitamin C supplementation is being administered as it should be considered a medication just like any other. We present a case of hemolysis in a glucose-6-phosphate dehydrogenase- (G6PD-) deficient patient receiving high-dose vitamin C infusions for his rheumatoid arthritis. PMID:29317868

Serum amyloid A and haptoglobin concentrations and liver fat percentage in lactating dairy cows with abomasal displacement.

Science.gov (United States)

Guzelbektes, H; Sen, I; Ok, M; Constable, P D; Boydak, M; Coskun, A

2010-01-01

There has been increased interest in measuring the serum concentration of acute phase reactants such as serum amyloid A [SAA] and haptoglobin [haptoglobin] in periparturient cattle in order to provide a method for detecting the presence of inflammation or bacterial infection. To determine whether [SAA] and [haptoglobin] are increased in cows with displaced abomasum as compared with healthy dairy cows. Fifty-four adult dairy cows in early lactation that had left displaced abomasum (LDA, n = 34), right displaced abomasum or abomasal volvulus (RDA/AV, n = 11), or were healthy on physical examination (control, n = 9). Inflammatory diseases or bacterial infections such as mastitis, metritis, or pneumonia were not clinically apparent in any animal. Jugular venous blood was obtained from all cows and analyzed. Liver samples were obtained by biopsy in cattle with abomasal displacement. [SAA] and [haptoglobin] concentrations were increased in cows with LDA or RDA/AV as compared with healthy controls. Cows with displaced abomasum had mild to moderate hepatic lipidosis, based on liver fat percentages of 9.3 +/- 5.3% (mean +/- SD, LDA) and 10.8 +/- 7.7% (RDA/AV). [SAA] and [haptoglobin] were most strongly associated with liver fat percentage, r(s) = +0.55 (P hepatic lipidosis in cattle with abomasal displacement.

Characterization of the abomasal transcriptome for mechanisms of resistance to gastrointestinal nematodes in cattle

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Li Robert W

2011-11-01

Full Text Available Abstract The response of the abomasal transcriptome to gastrointestinal parasites was evaluated in parasite-susceptible and parasite-resistant Angus cattle using RNA-seq at a depth of 23.7 million sequences per sample. These cattle displayed distinctly separate resistance phenotypes as assessed by fecal egg counts. Approximately 65.3% of the 23 632 bovine genes were expressed in the fundic abomasum. Of these, 13 758 genes were expressed in all samples tested and likely represent core components of the bovine abomasal transcriptome. The gene (BT14427 with the most abundant transcript, accounting for 10.4% of sequences in the transcriptome, is located on chromosome 29 and has unknown functions. Additionally, PIGR (1.6%, Complement C3 (0.7%, and Immunoglobulin J chain (0.5% were among the most abundant transcripts in the transcriptome. Among the 203 genes impacted, 64 were significantly over-expressed in resistant animals at a stringent cutoff (FDR

Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans

International Nuclear Information System (INIS)

McMahon, M.M.; Schwenk, W.F.; Haymond, M.W.; Rizza, R.A.

1989-01-01

Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently negative glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01)

Small volume resuscitation with hypertonic sodium chloride solution in cattle undergoing surgical correction of abomasal volvulus

DEFF Research Database (Denmark)

Sickinger, M.; Doll, K.; Roloff, N. C.

2014-01-01

.5±2.1 vs. 10.3±3.3cm H2O, respectively). Within the first 60min, the base excess decreased from 5.5±6.9 to 4.7±6.2mmol/L in the hypertonic group whereas it increased from 5.6±5.7 to 6.8±5.4mmol/L in the isotonic group. These results suggest that for cows with abomasal volvulus, IV therapy with hypertonic...... had a significantly greater reduction in volume deficit within the first 10min of therapy than cows treated with isotonic saline (from 5.9±4.8 to 2.1±4.4L/100kg vs. 7.0±4.5 to 4.9±3.8L/100kg, respectively). The central venous pressure (CVP) of the cows given the hypertonic saline rose within the first...... 10 min of therapy from 7.3±3.5 to 10.8±3.4cm H2O, while the CVP of the cattle treated with isotonic saline did not increase significantly during this time.Sixty minutes after the start of the infusion, the CVP of the isotonic group was still significantly lower than that of the hypertonic group (9...

Characterization of the abomasal transcriptome for mechanisms of resistance to gastrointestinal nematodes in cattle

Science.gov (United States)

2011-01-01

The response of the abomasal transcriptome to gastrointestinal parasites was evaluated in parasite-susceptible and parasite-resistant Angus cattle using RNA-seq at a depth of 23.7 million sequences per sample. These cattle displayed distinctly separate resistance phenotypes as assessed by fecal egg counts. Approximately 65.3% of the 23 632 bovine genes were expressed in the fundic abomasum. Of these, 13 758 genes were expressed in all samples tested and likely represent core components of the bovine abomasal transcriptome. The gene (BT14427) with the most abundant transcript, accounting for 10.4% of sequences in the transcriptome, is located on chromosome 29 and has unknown functions. Additionally, PIGR (1.6%), Complement C3 (0.7%), and Immunoglobulin J chain (0.5%) were among the most abundant transcripts in the transcriptome. Among the 203 genes impacted, 64 were significantly over-expressed in resistant animals at a stringent cutoff (FDR parasite resistance in cattle. Our results provide insights into the development of host immunity to gastrointestinal nematode infection and will facilitate understanding of mechanism underlying host resistance. PMID:22129081

Simultaneous determination of glucose turnover, alanine turnover, and gluconeogenesis in human using a double stable-isotope-labeled tracer infusion and gas chromatography-mass spectrometry analysis

International Nuclear Information System (INIS)

Martineau, A.; Lecavalier, L.; Falardeau, P.; Chiasson, J.L.

1985-01-01

We have developed and validated a new method to measure simultaneously glucose turnover, alanine turnover, and gluconeogenesis in human, in steady and non-steady states, using a double stable-isotope-labeled tracer infusion and GC-MS analysis. The method is based on the concomitant infusion and dilution of D-[2,3,4,6,6-2H5]glucose and L-[1,2,3-13C3]alanine. The choice of the tracers was done on the basis of a minimal overlap between the ions of interest and those arising from natural isotopic abundances. Alanine was chosen as the gluconeogenic substrate because it is the major gluconeogenic amino acid extracted by the liver and, with lactate, constitutes the bulk of the gluconeogenic precursors. The method was validated by comparing the results obtained during simultaneous infusion of trace amounts of both stable isotope labeled compounds with the radioactive tracers (D-[3-3H]glucose and L-[1,2,3-14C3]alanine) in a normal and a diabetic subject; the radiolabeled tracers were used as the accepted reference procedure. A slight overestimation of glucose turnover (7.3 versus 6.8 in normal and 10.8 versus 9.2 mumol/kg min in diabetic subject) was noticed when the stable isotope-labeled tracers were used. For the basal turnover rate of alanine, similar values were obtained with both methods (6.2 mumol/kg min). For gluconeogenesis, higher values were observed in the basal state with the stable isotopes (0.42 versus 0.21 mumol/kg min); however, these differences disappeared in the postprandial period after the ingestion of a mixed meal. Despite those minor differences, the overall correlation with the reference method was excellent for glucose turnover (r = 0.87) and gluconeogenesis (r = 0.86)

Exercise Protects Against Defective Insulin Signaling and Insulin Resistance of Glucose Transport in Skeletal Muscle of Angiotensin II-Infused Rat

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Juthamard Surapongchai

2018-04-01

Full Text Available Objectives: The present study investigated the impact of voluntary exercise on insulin-stimulated glucose transport and the protein expression and phosphorylation status of the signaling molecules known to be involved in the glucose transport process in the soleus muscle as well as other cardiometabolic risks in a rat model with insulin resistance syndrome induced by chronic angiotensin II (ANGII infusion.Materials and Methods: Male Sprague-Dawley rats were assigned to sedentary or voluntary wheel running (VWR groups. Following a 6-week period, rats in each group were subdivided and subcutaneously administered either normal saline or ANGII at 100 ng/kg/min for 14 days. Blood pressure, glucose tolerance, insulin-stimulated glucose transport and signaling proteins, including insulin receptor (IR, insulin receptor substrate 1 (IRS-1, Akt, Akt substrate of 160 kDa (AS160, AMPKα, c-Jun NH2-terminal kinase (JNK, p38 MAPK, angiotensin converting enzyme (ACE, ANGII type 1 receptor (AT1R, ACE2, Mas receptor (MasR and oxidative stress marker in the soleus muscle, were evaluated.Results: Exercise protected against the insulin resistance of glucose transport and defective insulin signaling molecules in the soleus muscle; this effect was associated with a significant increase in AMPK Thr172 (43% and decreases in oxidative stress marker (31% and insulin-induced p38 MAPK Thr180/Tyr182 (45% and SAPK/JNK Thr183/Tyr185 (25%, without significant changes in expression of AT1R, AT2R, ACE, ACE2, and MasR when compared to the sedentary rats given ANGII infusion. At the systemic level, VWR significantly decreased body weight, fat weight, and systolic blood pressure as well as improved serum lipid profiles.Conclusion: Voluntary exercise can alleviate insulin resistance of glucose transport and impaired insulin signaling molecules in the soleus muscle and improve whole-body insulin sensitivity in rats chronically administered with ANGII.

The relationship between gluconeogenic substrate supply and glucose production in humans

International Nuclear Information System (INIS)

Jahoor, F.; Peters, E.J.; Wolfe, R.R.

1990-01-01

The relationship between gluconeogenic precursor supply and glucose production has been investigated in 14-h and 86-h fasted humans. In protocols 1 and 2 [6,6-2H]glucose and [15N2]urea were infused to measure glucose and urea production rates (Ra) in response to infusions of glycerol and alanine. In protocol 3 first [15N]alanine, [3-13C]lactate, and [6,6-2H]glucose were infused before and during administration of dichloroacetate (DCA) to determine the response of glucose Ra to decreased fluxes of pyruvate, alanine, and lactate, then alanine was infused with DCA and glucose Ra measured. After a 14-h fast, neither alanine nor glycerol increased glucose Ra. Basal glucose Ra decreased by one-third after 86 h of fasting, yet glycerol and alanine infusions had no effect on glucose Ra. Glycerol always reduced urea Ra (P less than 0.05), suggesting that glycerol competitively inhibited gluconeogenesis from amino acids. DCA decreased the fluxes of pyruvate, alanine (P less than 0.01), and glucose Ra (P less than 0.01), which was prevented by alanine infusion. These findings suggest that (1) the reduction in glucose Ra after an 86-h fast is not because of a shortage of gluconeogenic substrate; (2) nonetheless, the importance of precursor supply to maintain basal glucose Ra is confirmed by the response to DCA; (3) an excess of one gluconeogenic substrate inhibits gluconeogenesis from others

Associations between bolus infusion of hydrocortisone, glycemic variability and insulin infusion rate variability in critically Ill patients under moderate glycemic control

NARCIS (Netherlands)

van Hooijdonk, Roosmarijn T. M.; Binnekade, Jan M.; Bos, Lieuwe D. J.; Horn, Janneke; Juffermans, Nicole P.; Abu-Hanna, Ameen; Schultz, Marcus J.

2015-01-01

We retrospectively studied associations between bolus infusion of hydrocortisone and variability of the blood glucose level and changes in insulin rates in intensive care unit (ICU) patients. 'Glycemic variability' and 'insulin infusion rate variability' were calculated from and expressed as the

A web-based study of the relationship of duration of insulin pump infusion set use and fasting blood glucose level in adults with type 1 diabetes.

Science.gov (United States)

Sampson Perrin, Alysa J; Guzzetta, Russell C; Miller, Kellee M; Foster, Nicole C; Lee, Anna; Lee, Joyce M; Block, Jennifer M; Beck, Roy W

2015-05-01

To evaluate the impact of infusion set use duration on glycemic control, we conducted an Internet-based study using the T1D Exchange's online patient community, Glu ( myGlu.org ). For 14 days, 243 electronically consented adults with type 1 diabetes (T1D) entered online that day's fasting blood glucose (FBG) level, the prior day's total daily insulin (TDI) dose, and whether the infusion set was changed. Mean duration of infusion set use was 3.0 days. Mean FBG level was higher with each successive day of infusion set use, increasing from 126 mg/dL on Day 1 to 133 mg/dL on Day 3 to 147 mg/dL on Day 5 (P<0.001). TDI dose did not vary with increased duration of infusion set use. Internet-based data collection was used to rapidly conduct the study at low cost. The results indicate that FBG levels increase with each additional day of insulin pump infusion set use.

Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1988-01-01

We previously demonstrated that conventional tracer methods applied to euglycemic-hyperinsulinemic glucose clamps result in substantially negative estimates for the rate of endogenous glucose production, particularly during the first half of 180-min clamps. We also showed that addition of tracer to the exogenous glucose infusate resulted in nonnegative endogenous glucose production (Ra) estimates. In this study, we investigated the underlying cause of negative estimates of Ra from conventional clamp/tracer methods and the reason for the difference in estimates when tracer is added to the exogenous glucose infusate. We performed euglycemic-hyperinsulinemic (300-microU/ml) clamps in normal dogs without (cold GINF protocol, n = 6) or with (hot GINF protocol, n = 6) tracer (D-[3-3H]glucose) added to the exogenous glucose infusate. In the hot GINF protocol, sufficient tracer was added to the exogenous glucose infusate such that arterial plasma specific activity (SAa) did not change from basal through the clamp period (P greater than .05). In the cold GINF studies, plasma SAa fell 81 +/- 2% from the basal level by the 3rd h of clamping. We observed a significant, transient, positive venous-arterial difference in specific activity (SAv-SAa difference) during the cold GINF studies. The SAv-SAa difference reached a peak of 27 +/- 6% at 30 min and diminished to a plateau of 7 +/- 1% between 70 and 180 min. We also observed a positive but constant SAv-SAa difference (4.6 +/- 0.2% between 10 and 180 min) during the hot GINF studies

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing

DEFF Research Database (Denmark)

Jensen, Vivi Flou Hjorth; Molck, Anne-Marie; Martensson, Martin

2017-01-01

compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model...... which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous...... infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model....

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

DEFF Research Database (Denmark)

Nielsen, Michael F; Caumo, Andrea; Chandramouli, Visvanathan

2004-01-01

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion...... resistance. Postabsorptive glucose production (P = 0.64) and the fractional....... Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

DEFF Research Database (Denmark)

Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

1999-01-01

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...... under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas...

In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting

Directory of Open Access Journals (Sweden)

Olmos Pablo R

2010-07-01

Full Text Available Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.

Glucose and fructose 6-phosphate cycle in humans

International Nuclear Information System (INIS)

Karlander, S.; Roovete, A.; Vranic, M.; Efendic, S.

1986-01-01

We have determined the rate of glucose cycling by comparing turnovers of [2- 3 H]- and [6- 3 H]glucose under basal conditions and during a glucose infusion. Moreover, the activity of the fructose 6-phosphate cycle was assessed by comparing [3- 3 H]- and [6- 3 H]glucose. The study included eight lean subjects with normal glucose tolerance. They participated in two randomly performed investigations. In one experiment [2- 3 H]- and [6- 3 H]glucose were given simultaneously, while in the other only [3- 3 H]glucose was given. The basal rate of glucose cycling was 0.32 +/- 0.08 mg X kg-1 X min-1 or 17% of basal glucose production (P less than 0.005). During glucose infusion the activity of endogenous glucose cycling did not change but since glucose production was suppressed it amounted to 130% of glucose production. The basal fructose 6-phosphate cycle could be detected only in three subjects and was suppressed during glucose infusion. In conclusion, the glucose cycle is active in healthy humans both in basal conditions and during moderate hyperglycemia. In some subjects, the fructose 6-phosphate cycle also appears to be active. Thus it is preferable to use [6- 3 H]glucose rather than [3- 3 H]glucose when measuring glucose production and particularly when assessing glucose cycle

Effect of i.v. dextrose administration on glucose metabolism during surgery.

Science.gov (United States)

Schricker, Thomas; Lattermann, Ralph; Wykes, Linda; Carli, Franco

2004-01-01

The inhibitory influence of exogenous dextrose on glucose production has been shown to be less pronounced during injury and sepsis. This protocol was designed to investigate the effect of i.v. hypocaloric dextrose on glucose metabolism during elective abdominal surgery. Fourteen patients with rectal cancer were studied under fasting conditions and toward the end of a 3-hour infusion of dextrose (2 mg.kg-1 per minute) either in absence (control group, n = 7) or presence of colonic surgery (surgery group, n = 7). Endogenous glucose production was determined by using primed continuous infusions of [6,6-2H2]glucose before and during dextrose administration. We also measured the plasma concentrations of glucose, lactate, cortisol, glucagon, and insulin. The administration of dextrose decreased the endogenous glucose production in all patients (p dextrose infusion in both groups (p Dextrose infusion increased the plasma insulin concentrations to the same extent in both groups (p dextrose on endogenous glucose production.

Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

International Nuclear Information System (INIS)

Bell, P.M.; Firth, R.G.; Rizza, R.A.

1986-01-01

To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man

Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

Science.gov (United States)

Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard

2016-11-01

To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-13C2]glucose.

Science.gov (United States)

Lai, Marta; Lanz, Bernard; Poitry-Yamate, Carole; Romero, Jackeline F; Berset, Corina M; Cudalbu, Cristina; Gruetter, Rolf

2017-01-01

In vivo 13 C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing 13 C-labeled glucose. Metabolic flux analysis of 13 C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, 13 C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6- 13 C 2 ]glucose for up to 5 h. 13 C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V g  = 0.16 ± 0.03 µmol/g/min) and neurons (V TCA n  = 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V PC  = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V NT  = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR glc ) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from 13 C direct detection with an unprecedented spatial resolution under [1,6- 13 C 2 ]glucose infusion.

Conjoint regulation of glucagon concentrations via plasma insulin and glucose in dairy cows.

Science.gov (United States)

Zarrin, M; Wellnitz, O; Bruckmaier, R M

2015-04-01

Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a suppressor of glucagon secretion. We have investigated if and how insulin and glucose contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG, n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin at simultaneously normal glucose concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin, and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area under the curve (AUC)/h in HypoG (41.9 ± 8.1 mU/L) and EuG (57.8 ± 7.8 mU/L) compared with NaCl (13.9 ± 1.1 mU/L; P insulin infusion induces elevated glucagon concentrations during hypoglycemia, although the same insulin infusion reduces glucagon concentrations at simultaneously normal glucose concentrations. Thus, insulin does not generally have an inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is high, glucagon is upregulated to increase glucose availability. Therefore, insulin and glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the plasma glucose status is the key factor to decide if its concentrations are increased or decreased. This regulatory effect can be important for the maintenance of glucose homeostasis if insulin secretion is upregulated by other factors than high

Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

International Nuclear Information System (INIS)

Radziuk, J.

1989-01-01

The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3- 3 H]glucose and a marker for gluconeogenesis, [U- 14 C]lactate or sodium [ 14 C]bicarbonate [ 14 C]bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6- 3 H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [ 14 C]glucose production or for dilution of 14 C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U- 14 C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [ 14 C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U- 14 C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [ 14 C]bicarbonate as tracer (P less than 0.05, vs. [ 14 C]-lactate as tracer). When [2- 14 C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14 CO 2 is a potentially useful marker for the gluconeogenetic process in vivo

Blood glucose response to rescue dextrose in hypoglycemic, critically ill patients receiving an insulin infusion.

Science.gov (United States)

Murthy, Manasa S; Duby, Jeremiah J; Parker, Patricia L; Durbin-Johnson, Blythe P; Roach, Denise M; Louie, Erin L

2015-08-01

There is inadequate guidance for clinicians on selection of the optimal dextrose 50% (D50W) dose for hypoglycemia correction in critically ill patients. The purpose of this study was to determine the blood glucose (BG) response to D50W in critically ill patients. A retrospective analysis was conducted of critically ill patients who received D50W for hypoglycemia (BG 150 mg/dL), resulting in a 6.8% rate of overcorrection; 49% of hypoglycemic episodes (230/470) corrected to a BG >100 mg/dL. A multivariable GEE analysis showed a significantly higher BG response in participants with diabetes (0.002) but a lower response in those with recurrent hypoglycemia (P = 0.049). The response to D50W increased with increasinginsulin infusion rate (P = 0.022). Burn patients experienced a significantly larger BG response compared with cardiac, medical, neurosurgical, or surgical patients. The observed median effect of D50W on BG was approximately 4 mg/dL per gram of D50W administered. Application of these data may aid in rescue protocol development that may reduce glucose variability associated with hypoglycemic episodes and the correction. © The Author(s) 2015.

Computer Simulation Model to Train Medical Personnel on Glucose Clamp Procedures.

Science.gov (United States)

Maghoul, Pooya; Boulet, Benoit; Tardif, Annie; Haidar, Ahmad

2017-10-01

A glucose clamp procedure is the most reliable way to quantify insulin pharmacokinetics and pharmacodynamics, but skilled and trained research personnel are required to frequently adjust the glucose infusion rate. A computer environment that simulates glucose clamp experiments can be used for efficient personnel training and development and testing of algorithms for automated glucose clamps. We built 17 virtual healthy subjects (mean age, 25±6 years; mean body mass index, 22.2±3 kg/m 2 ), each comprising a mathematical model of glucose regulation and a unique set of parameters. Each virtual subject simulates plasma glucose and insulin concentrations in response to intravenous insulin and glucose infusions. Each virtual subject provides a unique response, and its parameters were estimated from combined intravenous glucose tolerance test-hyperinsulinemic-euglycemic clamp data using the Bayesian approach. The virtual subjects were validated by comparing their simulated predictions against data from 12 healthy individuals who underwent a hyperglycemic glucose clamp procedure. Plasma glucose and insulin concentrations were predicted by the virtual subjects in response to glucose infusions determined by a trained research staff performing a simulated hyperglycemic clamp experiment. The total amount of glucose infusion was indifferent between the simulated and the real subjects (85±18 g vs. 83±23 g; p=NS) as well as plasma insulin levels (63±20 mU/L vs. 58±16 mU/L; p=NS). The virtual subjects can reliably predict glucose needs and plasma insulin profiles during hyperglycemic glucose clamp conditions. These virtual subjects can be used to train personnel to make glucose infusion adjustments during clamp experiments. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Estimation of liver glucose metabolism after refeeding

International Nuclear Information System (INIS)

Rognstad, R.

1987-01-01

Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

Effects of early rumen development and solid feed composition on growth performance and abomasal health in veal calves.

NARCIS (Netherlands)

Berends, H.; Reenen, van C.G.; Stockhofe, N.; Gerrits, W.J.J.

2012-01-01

The experiment was designed to study the importance of early rumen development and of the composition of solid feed intake on growth performance and abomasal health in milk-fed veal calves. One hundred and six Holstein-Friesian male calves were included in the experiment, and studied during 2

Glucose transport and milk secretion during manipulated plasma insulin and glucose concentrations and during LPS-induced mastitis in dairy cows.

Science.gov (United States)

Gross, J J; van Dorland, H A; Wellnitz, O; Bruckmaier, R M

2015-08-01

In dairy cows, glucose is essential as energy source and substrate for milk constituents. The objective of this study was to investigate effects of long-term manipulated glucose and insulin concentrations in combination with a LPS-induced mastitis on mRNA abundance of glucose transporters and factors involved in milk composition. Focusing on direct effects of insulin and glucose without influence of periparturient endocrine adaptations, 18 dairy cows (28 ± 6 weeks of lactation) were randomly assigned to one of three infusion treatments for 56 h (six animals each). Treatments included a hyperinsulinemic hypoglycaemic clamp (HypoG), a hyperinsulinemic euglycaemic clamp (EuG) and a control group (NaCl). After 48 h of infusions, an intramammary challenge with LPS from E. coli was performed and infusions continued for additional 8 h. Mammary gland biopsies were taken before, at 48 (before LPS challenge) and at 56 h (after LPS challenge) of infusion, and mRNA abundance of genes involved in mammary gland metabolism was measured by RT-qPCR. During the 48 h of infusions, mRNA abundance of glucose transporters GLUT1, 3, 4, 8, 12, SGLT1, 2) was not affected in HypoG, while they were downregulated in EuG. The mRNA abundance of alpha-lactalbumin, insulin-induced gene 1, κ-casein and acetyl-CoA carboxylase was downregulated in HypoG, but not affected in EuG. Contrary during the intramammary LPS challenge, most of the glucose transporters were downregulated in NaCl and HypoG, but not in EuG. The mRNA abundance of glucose transporters in the mammary gland seems not to be affected by a shortage of glucose, while enzymes and milk constituents directly depending on glucose as a substrate are immediately downregulated. During LPS-induced mastitis in combination with hypoglycaemia, mammary gland metabolism was more aligned to save glucose for the immune system compared to a situation without limited glucose availability during EuG. Journal of Animal Physiology and Animal

Lactate overrides central nervous but not beta-cell glucose sensing in humans.

Science.gov (United States)

Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

2008-12-01

Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

Effects of early rumen development and solid feed composition on growth performance and abomasal health in veal calves.

Science.gov (United States)

Berends, H; van Reenen, C G; Stockhofe-Zurwieden, N; Gerrits, W J J

2012-06-01

The experiment was designed to study the importance of early rumen development and of the composition of solid feed intake on growth performance and abomasal health in milk-fed veal calves. One hundred and six Holstein-Friesian male calves were included in the experiment, and studied during 2 successive 12-wk periods (period 1 and period 2). In a 2 × 2 factorial arrangement, effects of partially replacing milk replacer by solid feed during period 1 and partially replacing dry matter (DM) intake from maize silage and barley straw by concentrate during period 2 were tested. Solid feed during period 1 consisted of maize silage, barley straw, and concentrate (25:25:50 on a DM basis). Solid feed during period 2 consisted of maize silage and barley straw (50:50 ratio on DM basis) for the nonconcentrate groups, and maize silage, barley straw and concentrates (25:25:50 on a DM basis) for the concentrate groups. At the end of period 1 (n=16) and at the end of period 2 (n=90), parameters of animal performance, rumen development, rumen fermentation, ruminal drinking, and abomasal damage were examined. Partially replacing milk replacer by solid feed during period 1 resulted in early rumen development (ERD) at the end of period 1, characterized by increased rumen weight, and an increased epithelial and absorptive surface area. Both ERD and partially replacing roughage by concentrates in period 2 increased the rumen development score at the end of period 2. Although ERD calves consumed more solid feed and less milk replacer during period 1 and 2 than non-ERD calves, carcass weight gains at 25 wk were identical, and utilization of the solid feed provided appeared similar to that of milk replacer. Partially replacing roughage by concentrates in period 2 increased dressing percentage and warm carcass weight. Plaque formation at the rumen mucosa was unaffected by ERD or partially replacing roughage by concentrates and generally low in all calves. The prevalence of large scars in

Glucose production during exercise in humans

DEFF Research Database (Denmark)

Bergeron, R; Kjaer, M; Simonsen, L

1999-01-01

at 50.4 +/- 1.5(SE)% maximal O(2) consumption, followed by 30 min at 69.0 +/- 2.2% maximal O(2) consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood...... glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-(3)H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique......The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23-30 yr) performed semisupine cycling for 40 min...

Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

Science.gov (United States)

Piantoni, P; Allen, M S

2015-08-01

To evaluate propylene glycol (PG) and glycerol (G) as potential treatments for ketosis, we conducted 2 experiments lasting 4 d each in which cows received one bolus infusion per day. Blood was collected before infusion, over 240min postinfusion, as well as 24 h postinfusion. Experiment 1 used 6 ruminally cannulated cows (26±7 d in milk) randomly assigned to 300-mL infusions of PG or G (both ≥99.5% pure) in a crossover design experiment with 2 periods. Within each period, cows were assigned randomly to infusion site sequence: abomasum (A)-cranial reticulorumen (R) or the reverse, R-A. Glucose precursors were infused into the R to simulate drenching and the A to prevent metabolism by ruminal microbes. Glycerol infused in the A increased plasma glucose concentration the most (15.8mg/dL), followed by PG infused in the R (12.6mg/dL), PG infused in the A (9.11mg/dL), and G infused in the R (7.3mg/dL). Infusion of PG into the R increased plasma insulin and insulin area under the curve (AUC) the most compared with all other treatments (7.88 vs. 2.13μIU/mL and 321 vs. 31.9min×μIU/mL, respectively). Overall, PG decreased plasma BHBA concentration after infusion (-6.46 vs. -4.55mg/dL) and increased BHBA AUC (-1,055 vs. -558min ×mg/dL) compared with G. Plasma NEFA responses were not different among treatments. Experiment 2 used 8 ruminally cannulated cows (22±5 d in milk) randomly assigned to treatment sequence in a Latin square design experiment balanced for carryover effects. Treatments were 300mL of PG, 300mL of G, 600mL of G (2G), and 300mL of PG + 300mL of G (GPG), all infused into the R. Treatment contrasts compared PG with each treatment containing glycerol (G, 2G, and GPG). Propylene glycol increased plasma glucose (14.0 vs. 5.35mg/dL) and insulin (7.59 vs. 1.11μIU/mL) concentrations compared with G, but only tended to increase glucose and insulin concentrations compared with 2G. Propylene glycol increased AUC for glucose (1,444 vs. 94.3mg/dL) and insulin (326

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

NARCIS (Netherlands)

Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

2007-01-01

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

Human adipose tissue blood flow during prolonged exercise, III. Effect of beta-adrenergic blockade, nicotinic acid and glucose infusion

DEFF Research Database (Denmark)

Bülow, J

1981-01-01

acid, during acute i.v. beta-adrenergic blockade by propranolol, and during continuous i.v. infusion of glucose. The most pronounced lipid mobilization and utilization during work was seen in the control experiments where ATBF rose 3-fold on average from the initial rest period to the third hour...... of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did......Subcutaneous adipose tissue blood flow (ATBF) was measured in six male subjects by the 133Xe-washout technique during 3-4 h of exercise at a work load corresponding to an oxygen uptake of about 1.71/min. The measurements were done during control conditions, during blockade of lipolysis by nicotinic...

Glucose homeostasis in children with falciparum malaria: precursor supply limits gluconeogenesis and glucose production

NARCIS (Netherlands)

Dekker, E.; Hellerstein, M. K.; Romijn, J. A.; Neese, R. A.; Peshu, N.; Endert, E.; Marsh, K.; Sauerwein, H. P.

1997-01-01

To evaluate glucose kinetics in children with falciparum malaria, basal glucose production and gluconeogenesis and an estimate of the flux of the gluconeogenic precursors were measured in Kenyan children with uncomplicated falciparum malaria before (n = 11) and during infusion of alanine (1.5

Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate

Science.gov (United States)

Deelchand, Dinesh K.; Nelson, Christopher; Shestov, Alexander A.; Uğurbil, Kâmil; Henry, Pierre-Gilles

2009-02-01

In this work the feasibility of measuring neuronal-glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate was investigated. Time courses of 13C spectra were measured in vivo while infusing both 13C-labeled substrates simultaneously. Individual 13C isotopomers (singlets and multiplets observed in 13C spectra) were quantified automatically using LCModel. The distinct 13C spectral pattern observed in glutamate and glutamine directly reflected the fact that glucose was metabolized primarily in the neuronal compartment and acetate in the glial compartment. Time courses of concentration of singly and multiply-labeled isotopomers of glutamate and glutamine were obtained with a temporal resolution of 11 min. Although dynamic metabolic modeling of these 13C isotopomer data will require further work and is not reported here, we expect that these new data will allow more precise determination of metabolic rates as is currently possible when using either glucose or acetate as the sole 13C-labeled substrate.

Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

Science.gov (United States)

Kloster, Brian O; Lund, Lars; Lindholt, Jes S

2016-05-01

The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

Clinical value of Flash glucose monitoring in patients with type 1 diabetes treated with continuous subcutaneous insulin infusion.

Science.gov (United States)

Moreno-Fernandez, Jesus; Pazos-Couselo, Marcos; González-Rodriguez, Maria; Rozas, Pedro; Delgado, Manuel; Aguirre, Miguel; Garcia-Lopez, Jose Manuel

2018-06-12

To analyze the clinical impact of the Flash glucose monitoring system in patients with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). A 24-week retrospective cohort study in CSII-treated T1DM patients exposed (1:1) to the Flash glucose monitoring system vs. self-monitoring of capillary blood glucose (SMBG). The primary outcome was the difference in hemoglobin A1c (HbA1c) levels between both groups at the end of the study. Thirty-six patients with a mean age of 38.2 years (range 22-55) and a mean T1DM duration of 20.9±7.8 years, treated with CSII for 7.1±5.4 years, were enrolled into the study. At the end of the study, mean HbA1c levels improved in patients in the Flash group (7.1±0.7 vs. 7.8±1.0, p=0.04). Only the Flash group showed a significant decrease in HbA1c levels of -0.4% (95% CI, -0.6, -0.2; p=0.004) during follow-up. Flash patients captured 93.9% of data through 17.8±9.9 scans daily. In fact, the Flash cohort showed a three-fold increase in daily self-monitoring of glucose, while daily frequency of SMBG decreased during the study (-1.8 tests/24h (95% CI -3, -0.7; p=0.01). No safety issues related to Flash use were recorded. The Flash glucose monitoring system is a novel approach to improve blood glucose control in CSII-treated T1DM patients. Randomized controlled trials are needed to assess the effectiveness of this system in CSII-treated T1DM patients. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

Science.gov (United States)

Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

2015-09-01

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (pglucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (pmemory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. Copyright © 2015 Elsevier Inc. All rights

Exogenous glucagon-like peptide-1 attenuates glucose absorption and reduces blood glucose concentration after small intestinal glucose delivery in critical illness.

Science.gov (United States)

Miller, Asaf; Deane, Adam M; Plummer, Mark P; Cousins, Caroline E; Chapple, Lee-Anne S; Horowitz, Michael; Chapman, Marianne J

2017-03-01

To evaluate the effect of exogenous glucagonlike peptide-1 (GLP-1) on small intestinal glucose absorption and blood glucose concentrations during critical illness. A prospective, blinded, placebo-controlled, cross-over, randomised trial in a mixed medical-surgical adult intensive care unit, with 12 mechanically ventilated critically ill patients, who were suitable for receiving small intestinal nutrient. On consecutive days, in a randomised order, participants received intravenous GLP-1 (1.2 pmol/ kg/min) or placebo (0.9% saline) as a continuous infusion over 270 minutes. After 6 hours of fasting, intravenous infusions of GLP-1 or placebo began at T = -30 min (in which T = time), with the infusion maintained at a constant rate until study completion at T = 240 min. At T = 0 min, a 100 mL bolus of mixed liquid nutrient meal (1 kcal/mL) containing 3 g of 3-O-methyl-D-gluco-pyranose (3-OMG), a marker of glucose absorption, was administered directly into the small intestine, via a post-pyloric catheter, over 6 minutes. Blood samples were taken at regular intervals for the measurement of plasma glucose and 3-OMG concentrations. Intravenous GLP-1 attenuated initial small intestinal glucose absorption (mean area under the curve [AUC] 0-30 for 3-OMG: GLP-1 group, 4.4 mmol/L/min [SEM, 0.9 mmol/L/min] v placebo group, 6.5 mmol/L/min [SEM, 1.0 mmol/L/min]; P = 0.01), overall small intestinal glucose absorption (mean AUC 0-240 for 3-OMG: GLP-1, 68.2 mmol/L/ min [SEM, 4.7 mmol/L/min] v placebo, 77.7 mmol/L/min [SEM, 4.4 mmol/lLmin]; P = 0.02), small intestinal glucose absorption and overall blood glucose concentration (mean AUC 0-240 for blood glucose: GLP-1, 2062 mmol/L/min [SEM, 111 mmol/L/min] v placebo 2328 mmol/L/min [SEM, 145 mmol/L/min]; P = 0.005). Short-term administration of exogenous GLP-1 reduces small intestinal glucose absorption for up to 4 hours during critical illness. This is likely to be an additional mechanism for the glucose-lowering effect of this agent.

Adrenergic blockade does not abolish elevated glucose turnover during bacterial infection

International Nuclear Information System (INIS)

Hargrove, D.M.; Bagby, G.J.; Lang, C.H.; Spitzer, J.J.

1988-01-01

Infusions of adrenergic antagonists were used to investigate the role of catecholamines in infection-induced elevations of glucose kinetics. Infection was produced in conscious catheterized rats by repeated subcutaneous injections of live Escherichia coli over 24 h. Glucose kinetics were measured by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose. Compared with noninfected rats, infected animals were hyperthermic and showed increased rates of glucose appearance, clearance, and recycling as well as mild hyperlacticacidemia. Plasma catecholamine concentrations were increased by 50-70% in the infected rats, but there were no differences in plasma glucagon, corticosterone, and insulin levels. Adrenergic blockade was produced by primed constant infusion of both propranolol (β-blocker) and phentolamine (α-blocker). A 2-h administration of adrenergic antagonists did not attenuate the elevated glucose kinetics or plasma lactate concentration in the infected rats, although it abolished the hyperthermia. In a second experiment, animals were infused with propranolol and phentolamine beginning 1 h before the first injection of E. coli and throughout the course of infection. Continuous adrenergic blockade failed to attenuate infection-induced elevations in glucose kinetics and plasma lactate. These results indicate that the adrenergic system does not mediate the elevated glucose metabolism observed in this mild model of infection

Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

International Nuclear Information System (INIS)

Stevenson, R.W.; Steiner, K.E.; Hendrick, G.K.; Cherrington, A.D.

1987-01-01

The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3- 3 H]glucose, glucose production (R a ) and utilization (R d ) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 μg·kg -1 ·min -1 ) was infused with intraportal replacement amounts of glucagon and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant for 250 min. Plasma glucagon was similar before and during somatostatin infusion, while plasma insulin was lower. Plasma glucose levels remained similar while R a and R d and the ratio of glucose clearance to plasma insulin were significantly increased. Net hepatic lactate uptake and [ 14 C]alanine plus [ 14 C]lactate conversion to [ 14 C]glucose increased. In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism

Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations

DEFF Research Database (Denmark)

Nauck, M A; Bartels, E; Orskov, C

1993-01-01

. The combination of GIP and GLP-1 led to B-cell responses that were significantly higher than those with either hormone alone (additive mode of cooperation). Plasma GIP concentrations were similar after endogenous secretion (oral glucose) and i.v. infusion, while exogenously administered GLP-1 led to plasma levels...

Enhanced glucose cycling and suppressed de novo synthesis of glucose-6-phosphate result in a net unchanged hepatic glucose output in ob/ob mice

NARCIS (Netherlands)

Bandsma, RHJ; Grefhorst, A; van Dijk, TH; van der Sluijs, FH; Hammer, A; Reijngoud, DJ; Kuipers, F

2004-01-01

Aims/hypothesis. Leptin-deficient ob/ob mice are hyperinsulinaemic and hyperglycaemic; however, the cause of hyperglycaemia remains largely unknown. Methods. Glucose metabolism in vivo in 9-h fasted ob/ob mice and lean littermates was studied by infusing [U-C-13]-glucose, [2-C-13]-glycerol,

The effect of caffeine on glucose kinetics in humans - influence of adrenaline

DEFF Research Database (Denmark)

Battram, Danielle S.; Graham, Terry E.; Richter, Erik

2005-01-01

While caffeine impedes insulin-mediated glucose disposal in humans, its effect on endo-genous glucose production (EGP) remains unknown. In addition, the mechanism involved in these effects is unclear, but may be due to the accompanying increase in adrenaline concentration. We studied the effect...... of caffeine on EGP and glucose infusion rates (GIR), and whether or not adrenaline can account for all of caffeine's effects. Subjects completed three isoglycaemic-hyperinsulinaemic clamps (with 3-[3H]glucose infusion) 30 min after ingesting: (1) placebo capsules (n= 12); (2) caffeine capsules (5 mg kg-1) (n......= 12); and either (3) placebo plus a high-dose adrenaline infusion (HAdr; adrenaline concentration, 1.2 nM; n= 8) or (4) placebo plus a low-dose adrenaline infusion (LAdr; adrenaline concentration, 0.75 nM; n= 6). With caffeine, adrenaline increased to 0.6 nM but no effect on EGP was observed. While...

Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

International Nuclear Information System (INIS)

Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

1987-01-01

In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R d ) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R d . In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using [3- 3 H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R d

[A Case of HPN, In Which QOL Improvement Was Achieved by Combining Continuous Infusion with Once-Weekly Intermittent Infusion - Contribution of Pharmacists to Health Promotion among Home Patients Receiving Infusion Therapy].

Science.gov (United States)

Takeda, Namihiro; Hamana, Tomoko; Oka, Toyoka; Hirohara, Masayoshi; Kushida, Kazuki

2016-12-01

Patients receiving parenteral nutrition at home have the following two options: 24-h continuous or intermittent infusion. To date, for patients with impaired glucose tolerance and/or other metabolic disorders or for those with decreased cardiac/ pulmonary/renal function, it is desirable to opt for continuous infusion to minimize the variance in the body's metabolic rate as much as possible. Furthermore, it should be noted that continuous infusion evokes a stronger feeling among patients of being constrained because it restricts their everyday activities. This case witnesses collaborations among the patient's doctor, dispensary's pharmacy, and patient's family. Because ofthe use ofintermittent infusion more or less once per week in addition to continuous infusion, significant improvement in quality of life was achieved, and the patient was able to enjoy taking a short trip. To assist a home patient receiving infusion therapy, it is essential that the pharmacist be equipped with skills to manage risks associated with infusion therapy and have knowledge about insurance to cover incidents concerning infusion fluids or medical materials. It will certainly depend on the degree ofindependence ofpatients and the level ofcare their families can provide; however, should we manage to use a similar medical procedure in at least a few cases in the future, we may be able to contribute to "joie de vivre" in home patients receiving infusion therapy.

Mesenteric blood flow, glucose absorption and blood pressure responses to small intestinal glucose in critically ill patients older than 65 years.

Science.gov (United States)

Sim, Jennifer A; Horowitz, M; Summers, M J; Trahair, L G; Goud, R S; Zaknic, A V; Hausken, T; Fraser, J D; Chapman, M J; Jones, K L; Deane, A M

2013-02-01

To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in individuals older than 65 years with, and without, critical illness. Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min; P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min; P AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min; P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29; P 65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.

The effects of TNF-α on GLP-1-stimulated plasma glucose kinetics

DEFF Research Database (Denmark)

Lehrskov-Schmidt, Louise; Lehrskov-Schmidt, Lars; Nielsen, Signe T

2015-01-01

levels impairs GLP-1's effects on glucose metabolism. Design: Randomized, controlled, cross-over trial. Setting: Hospital clinical research laboratory. Participants: Twelve healthy males (age 24±3 y; BMI 22.9±1.3 kg/m(2)). Interventions: Following an overnight fast, either saline (0.9%) or recombinant......Context: GLP-1 analogues have recently been promoted as anti-hyperglycemic agents in critically ill patients with systemic inflammation, but the effects of TNF-α on glucose metabolism during GLP-1 administration are unknown. Objective: To determine whether infusion of TNF-α at high physiological...... human TNF-α (1000 ng/m(2)/h) was infused from t = 0-6 hours. At t = 2 hours, GLP-1 infusion (0.5 pmol/kg/min) began. From t = 4-6 hours, the GLP-1 infusion rate was increased to 1.2 pmol/kg/min. Plasma glucose was clamped at 5 mmol/L throughout via a variable-rate 20% dextrose infusion. Trials were 7...

Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

Science.gov (United States)

Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

2013-11-01

Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose

NARCIS (Netherlands)

Grasman, Johan; Callender, Hannah L.; Mensink, Marco; Pietropaolo, Massimo

2017-01-01

A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level

Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man

DEFF Research Database (Denmark)

Hvidberg, A; Nielsen, M T; Hilsted, J

1994-01-01

at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol....../L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma...... insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during...

Distribution and kinetics of glucose in rats analyzed by noncompartmental and compartmental analysis

International Nuclear Information System (INIS)

Raman, M.; Radziuk, J.; Hetenyi, G. Jr.

1990-01-01

The steady-state kinetics and distribution of glucose were assessed using noncompartmental and various two-compartment models in rats that were infused with insulin (+/- euglycemic clamping), methylprednisolone (MP), or phlorizin (PHL) as well as rats injected with protamine-zinc-insulin (PZI) or rendered diabetic. Decreases in clearance of glucose (PCR) were greatest with insulin infusion, followed by PHL, MP, and PZI treatments. PCR decreased in diabetes to 25% of normal. With hyperinsulinemia and euglycemia, turnover rates were 1.18 times the rate of glucose infusion. In normal rats the ratio of the contents of the two compartments was 0.6-0.8 (depending on the model). Significant increases, of between 2.8 and 5.2, were observed with insulin infusion and between 0.8 and 1.8 with PHL, again depending on the model. Because PHL-induced changes in PCR are renal, these data suggest that variations in glucose distribution depend on changes in PCR as well as insulin. The intercompartmental rate constant decreased, and the noncompartmental volume of distribution increased to reflect the above changes. In non-steady-state studies, glucose release increased in response to insulin but not to PHL in contrast to other species

Intravenous glucose intake independently related to intensive care unit and hospital mortality : an argument for glucose toxicity in critically ill patients

NARCIS (Netherlands)

van der Voort, PHJ; Feenstra, RA; Bakker, AJ; de Heide, L; Boerma, EC; van der Horst, ICC

Objective It is assumed that the toxic effects of glucose play a role in the outcome of critically ill patients. We studied the impact of the amount of infused glucose as a determinant of mortality. Design A retrospective cohort study design was used as blood glucose levels in critically ill

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

Science.gov (United States)

Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

Estimation of glucose carbon recycling in children with glycogen storage disease: A 13C NMR study using [U-13C]glucose

International Nuclear Information System (INIS)

Kalderon, B.; Korman, S.H.; Gutman, A.; Lapidot, A.

1989-01-01

A stable isotope procedure to estimate hepatic glucose carbon recycling and thereby elucidate the mechanism by which glucose is produced in patients lacking glucose 6-phosphatase is described. A total of 10 studies was performed in children with glycogen storage disease type I (GSD-I) and type III (GSD-III) and control subjects. A primed dose-constant nasogastric infusion of D-[U- 13 C]glucose or an infusion diluted with nonlabeled glucose solution was administered following different periods of fasting. Hepatic glucose carbon recycling was estimated from 13 C NMR spectra. The values obtained for GSD-I patients coincided with the standard [U- 13 C]glucose dilution curve. These results indicate that the plasma glucose of GSD-I subjects comprises only a mixture of 99% 13 C-enriched D-[U- 13 C]glucose and unlabeled glucose but lacks any recycled glucose. Significantly different glucose carbon recycling values were obtained for two GSD-III patients in comparison to GSD-I patients. The results eliminate a mechanism for glucose production in GSD-I children involving gluconeogenesis. However, glucose release by amylo-1,6-glucosidase activity would result in endogenous glucose production of non- 13 C-labeled and nonrecycled glucose carbon, as was found in this study. In GSD-III patients gluconeogenesis is suggested as the major route for endogenous glucose synthesis. The contribution of the triose-phosphate pathway in these patients has been determined

Amino acid infusion during anesthesia attenuates the surgery induced decline in IGF-1 and diminishes the "diabetes of injury"

Directory of Open Access Journals (Sweden)

Eksborg Staffan

2007-01-01

Full Text Available Abstract Background Surgery, commonly performed after an overnight fast, causes a postoperative decline in the anabolic and glucose lowering insulin-like growth factor-1 (IGF-1. Clinical fasting studies have exhibited a positive correlation between IGF-1 and nitrogen balance during different conditions. A perioperative amino acid infusion changes nitrogen balance and might thereby influence serum IGF-1. We hypothesized that amino acid infusion would enhance IGF-1 and thereby might influence glucose homeostasis after surgery. In this study we examined two different regimes of perioperative amino acids infusion. Methods 24 females scheduled for abdominal hysterectomy were randomized into three groups; Ringer's solution infusion throughout anesthesia (Group B, amino acid infusion throughout anesthesia (Group C and amino acid infusion 1 hour before anesthesia and during 1.5 hrs of surgery (Group D. Six female volunteers, who were not operated, but received the same amino acids infusion after fasting, served as controls (Group A. Fasting levels of IGF-1, Insulin-like growth factor binding protein-1 (IGFBP-1, insulin and P-glucose were studied prior to, and four days following, operation. Homeostasis model assessment (HOMA was used as an index of insulin resistance. Non-parametric statistical methods were used. Results During the study the Ringer-group exhibited a decrease in IGF-1 and an increase in insulin and plasma glucose after surgery. Within the other groups there were no significant alterations over time after surgery, with the exception of a postoperative decrease in IGF-1 in group D. Group C had higher IGF-1 levels compared to group B on all days. Also, group D had higher IGF-1 levels than group B on day 2 – 4. From baseline to the first postoperative day there was a significant increase in HOMA and IGFBP-1 in groups B and C. These changes were not found in group D, in which insulin, glucose, HOMA and IGFBP-1 did not change. Amino acid

Hepatic glycogen in humans. I. Direct formation after oral and intravenous glucose or after a 24-h fast

International Nuclear Information System (INIS)

Radziuk, J.

1989-01-01

The formation of hepatic glycogen by the direct pathway is assessed in humans after a 12-h fast and oral loading (100 g) or intravenous infusion (90 g) and after a 24-h fast and the same oral glucose load. The methodology used is based on the double tracer method. [3- 3 H]glucose is infused at a constant rate for the determination of the metabolic clearance of glucose. [1- 14 C]glucose is administered with the glucose load. One hour after absorption or the intravenous glucose infusion is terminated, a glucagon infusion is initiated to mobilize the glycogen labeled with [1- 14 C]glucose and formed during the absorptive period. At this time a third tracer, [6- 3 H]glucose, is administered to measure glucose clearance. It was found that after the 12-h fast and oral glucose loading 7.2 +/- 1.1 g of hepatic glycogen appears to be formed directly from glucose compared with 8.4 +/- 1.0 g after the same load and a 24-h fast and 8.5 +/- 0.4 g after a 12-h fast and an equivalent intravenous glucose infusion. When the amount of label ([ 14 C]glucose) mobilized that was not corrected for metabolic recycling was calculated, the data suggested that the amount of glycogen formed by gluconeogenic pathways was probably at least equal to that formed by direct uptake. It was also approximately 60% greater after a 24-h fast. It can be concluded that the amount of hepatic glycogen formed directly from glucose during glucose loading is not significantly altered by the route of entry or the extension of the fasting period to 24 h. The data suggest, however, that gluconeogenetic formation of glycogen increases with fasting

The use of dextrose/insulin infusions during labour and delivery in women with gestational diabetes mellitus: Is there any point?

Science.gov (United States)

Farrant, Maritza T; Williamson, Kathryn; Battin, Malcolm; Hague, William M; Rowan, Janet A

2017-06-01

We compared, in 733 women with gestational diabetes mellitus treated with metformin and/or insulin, rates of neonatal hypoglycaemia in those who had received a dextrose/insulin infusion during labour and prior to delivery (n = 132) with those who did not (n = 601). Women who had infusions were more likely to have been treated with insulin (87.1% vs 70.4%, P < 0.01) and have higher mean capillary glucose values (measured four times daily) in the two weeks prior to delivery (P < 0.01). They had lower mean (SD) glucose values in the 12 h prior to delivery (5.1 (1.1) mmol/L vs 5.4 (0.9) mmol/L, P < 0.01). There was no difference between the groups in rates of neonatal hypoglycaemia (glucose <2.6 mmol/L on two or more occasions), 15.9% versus 17.8%, P = 0.78, or of severe neonatal hypoglycaemia (one or more glucose <1.6 mmol/L), 8.3% versus 5.2%, P = 0.15. In the absence of randomised data comparing use of infusions with no infusions, these data are reassuring for clinicians who do not routinely use infusions. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Glucose-dependent Insulinotropic Polypeptide

DEFF Research Database (Denmark)

Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

2014-01-01

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses......: During fasting glycemia (plasma glucose ∼8 mmol/L), GIP elicited significant increments in both insulin and glucagon levels, resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/L), GIP elicited a minor early-phase insulin response and increased...... glucagon levels during the initial 30 minutes, resulting in less glucose needed to be infused to maintain the clamp (29 ± 8 vs 49 ± 12 mg × kg(-1), P glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon...

Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alters blood metabolites, rumen fermentation, and nitrogen balance of beef steers.

Science.gov (United States)

Löest, C A; Gilliam, G G; Waggoner, J W; Turner, J L

2018-04-27

Steers exposed to an endotoxin may require additional branched-chain AA (BCAA) to support an increase in synthesis of immune proteins. This study evaluated effects of bacterial lipopolysaccharide (LPS) and BCAA supplementation on blood metabolites and N balance of 20 ruminally-cannulated steers (177 ± 4.2 kg BW). The experiment was a randomized block design, with 14-d adaptation to metabolism stalls and diet (DM fed = 1.5% BW) and 6-d collection. Treatments were a 2 × 2 factorial of LPS (0 vs 1.0 to 1.5 μg/kg BW; -LPS vs +LPS) and BCAA (0 vs 35 g/d; -BCAA vs +BCAA). The LPS in 100 mL sterile saline was infused (1 mL/min via i.v. catheter) on d 15. The BCAA in an essential AA solution were abomasally infused (900 mL/d) 3 times daily in equal portions beginning on d 7. Blood, rumen fluid, and rectal temperature were collected on d 15 at h 0, 2, 4, 8, 12, and 24 after LPS infusion. Feces and urine were collected from d 16 to 20. Rectal temperatures were greater for +LPS vs. -LPS steers at 4 h and lower at 8 h after LPS infusion (LPS h, P BCAA than -BCAA steers at 12 h after LPS infusion (BCAA × h, P BCAA, P BCAA than -BCAA steers at 0 h and 24 h after LPS infusion (BCAA × h, P ≤ 0.05). Steers receiving +LPS had lower rumen pH at 8 h, greater total VFA at 8 h, and lower rumen NH3 at 24 h after LPS infusion compared with -LPS steers (LPS × h, P ≤ 0.04). Total tract passage rates, DM, OM, NDF, ADF, and N intake, fecal N, digested N, and retained N were lower (P BCAA vs -BCAA steers. The absence of LPS × BCAA interactions (P ≥ 0.20) for N balance indicated that post-ruminal supplementation of BCAA did not alleviate the negative effects of endotoxin on N utilization by growing steers.

Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

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Everman, Sarah; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

2015-01-01

Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion. Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P BCAA in either of the experiments (P > 0.05). Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

Directory of Open Access Journals (Sweden)

Sarah Everman

Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine.

Science.gov (United States)

Sadri, Hassan; von Soosten, Dirk; Meyer, Ulrich; Kluess, Jeannette; Dänicke, Sven; Saremi, Behnam; Sauerwein, Helga

2017-01-01

Leucine (Leu), one of the three branch chain amino acids, acts as a signaling molecule in the regulation of overall amino acid (AA) and protein metabolism. Leucine is also considered to be a potent stimulus for the secretion of insulin from pancreatice β-cells. Our objective was to study the effects of a duodenal bolus infusion of Leu on insulin and glucagon secretion, on plasma AA concentrations, and to do a metabolomic profiling of dairy cows as compared to infusions with either glucose or saline. Six duodenum-fistulated Holstein cows were studied in a replicated 3 × 3 Latin square design with 3 periods of 7 days, in which the treatments were applied at the end of each period. The treatments were duodenal bolus infusions of Leu (DIL; 0.15 g/kg body weight), glucose (DIG; at Leu equimolar dosage) or saline (SAL). On the day of infusion, the treatments were duodenally infused after 5 h of fasting. Blood samples were collected at -15, 0, 10, 20, 30, 40, 50, 60, 75, 90, 120, 180, 210, 240 and 300 min relative to the start of infusion. Blood plasma was assayed for concentrations of insulin, glucagon, glucose and AA. The metabolome was also characterized in selected plasma samples (i.e. from 0, 50, and 120 min relative to the infusion). Body weight, feed intake, milk yield and milk composition were recorded throughout the experiment. The Leu infusion resulted in significant increases of Leu in plasma reaching 20 and 15-fold greater values than that in DIG and SAL, respectively. The elevation of plasma Leu concentrations after the infusion led to a significant decrease (Pcows were reduced (Pinsulin were not affected by Leu. In DIG, insulin and glucose concentrations peaked at 30-40 and 40-50 min after the infusion, respectively. Insulin concentrations were greater (Pcows were compared with the DIG and SAL cows at 50 and 120 min after the infusion. By using this analysis, several metabolites, mainly acylcarnitines, methionine sulfoxide and components from the

Insulin secretion after short- and long-term low-grade free fatty acid infusion in men with increased risk of developing type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Jensen, Christine B; Vaag, Allan A

2003-01-01

We studied the effect of a low-grade short- and long-term 20% Intralipid infusion (0.4 mL(-1) x kg(-1) x h(-1)) on insulin secretion and insulin action in 15 elderly obese men; 7 glucose intolerant first-degree relatives of type 2 diabetic patients (impaired glucose tolerance [IGT] relatives) and 8...... healthy controls of similar age and body mass index (BMI). Intravenous glucose tolerance test (IVGTT) and a graded glucose infusion (dose-response test [DORE]) were performed to determine first phase insulin response and to explore the dose response relationship between glucose concentration and insulin...... secretion rates (ISR). ISR were calculated by deconvolution of plasma C-peptide concentrations. Insulin action was determined by performing a 120-minute hyperinsulinemic euglycemic clamp. All tests were performed 3 times, preceded by 0, 2, or 24 hours Intralipid infusion. Disposition indices (DI) were...

Glucose modulates food-related salience coding of midbrain neurons in humans.

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Ulrich, Martin; Endres, Felix; Kölle, Markus; Adolph, Oliver; Widenhorn-Müller, Katharina; Grön, Georg

2016-12-01

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

In vitro and in vivo assessment of anti-hyperglycemic and antioxidant effects of Oak leaves (Quercus convallata and Quercus arizonica) infusions and fermented beverages.

Science.gov (United States)

Gamboa-Gómez, Claudia I; Simental-Mendía, Luis E; González-Laredo, Rubén F; Alcantar-Orozco, Esteban J; Monserrat-Juarez, Victor H; Ramírez-España, Julio C; Gallegos-Infante, Jose Alberto; Moreno-Jiménez, Martha R; Rocha-Guzmán, Nuria E

2017-12-01

The aim of this study was to evaluate the anti-hyperglycemic and antioxidant effects of oak leaves infusions and fermented beverages from Quercus convallata and Q. arizonica in vitro and in vivo. Female C57BL/6 mice fed with high saturated fat and fructose diet-induced obesity were treated with oak leaves beverages (200 μL/per day equivalent to 15mg of lyophilized sample/Kg of body weight for infusions and 31mg of lyophilized sample/Kg of body weight for fermented beverages) for 3months and an oral glucose tolerance test (OGTT) was performed. Blood plasma was obtained for determination of glucose, lipid profile, and oxidative stress markers (ABTS, nitric oxide, and ORAC assays). Insulin resistance was estimated using the product of triglycerides and glucose (TyG). Oak leaves infusions and fermented beverages exhibited exerted inhibition of α-amylase (8-15% and 5-9%, respectively) and α-glucosidase (98% and 99%, respectively) enzymes. After OGTT, the groups treated with either oak leaves infusions or fermented beverages showed lower glucose levels compared with the obesity control group (18%) and a similar glucose tolerance to healthy control group. On long-term evaluation, intervention groups showed a significant reduction in fasting glucose concentrations (41-50% for oak leaves infusions and 52-66% for fermented beverages) and TyG index (4.2-4.6% for oak leaves infusions and 5.9-7.5% for fermented beverages) compared with the obese control group. Oak leaves infusions and fermented beverages had antioxidant potential in vitro and scavenging activity for radicals such as peroxyl and peroxynitrite anions. Our results suggest anti-hyperglycemic and antioxidant effects of beverages prepared with leaves of Quercus species in vitro and in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pre-exercise blood glucose affects glycemic variation of aerobic exercise in patients with type 2 diabetes treated with continuous subcutaneous insulin infusion.

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Hu, Yun; Zhang, Dan-Feng; Dai, Lu; Li, Zheng; Li, Hui-Qin; Li, Feng-Fei; Liu, Bing-Li; Sun, Xiao-Juan; Ye, Lei; He, Ke; Ma, Jian-Hua

2018-05-03

Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC 0-60 min ). The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC 0-60 min (standardized β = -0.386, P AUC of blood glucose ≤ 4.4 mmol/L (standardized β = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P AUC 0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P  16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. ChiCTR-ONC-17010400, www.chictr.org.cn. Copyright © 2018 Elsevier B.V. All rights reserved.

The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance regain through pancreatic function recovery in streptozotocin-induced glucose-intolerant rats.

Science.gov (United States)

Dias, Teresa; Bronze, Maria Rosário; Houghton, Peter J; Mota-Filipe, Hélder; Paulo, Alexandra

2010-11-11

Infusions of Coreopsis tinctoria Nutt. flowering tops have been used traditionally in Portugal to control hyperglycaemia and a previous study revealed that daily administration of the infusion during a 3-week period promoted the recovery of glucose tolerance by a mechanism different from inhibition of glucose absorption and direct promotion of insulin secretion. We know report the study of the ethyl acetate fraction of Coreopsis tinctoria flowers infusion aiming to confirm flavonoids as bioactive metabolites. To give one step forward into the antihyperglycaemic mechanism of action of this traditionally used plant we also studied the activity of Coreopsis tinctoria flavonoids on the pancreatic function of glucose-intolerant rats. A standard antioxidant, Trolox, was also studied for comparative purposes as the antioxidant mechanism has been frequently purposed as one of the mechanisms mediating antihyperglycaemic effects of flavonoid-rich extracts. Thirteen compounds, mainly of flavanone and chalcone flavonoidal type, have been identified in this fraction by HPLC-DAD-ESI-MS/MS, and the major one (marein) quantified by HPLC-UV. The fraction (125 mg containing 20 mg of marein/kg b.w.) and Trolox (50 mg/kg b.w.) were administered daily by oral gavage to normal and STZ (40 mg/kg b.w.)-induced glucose-intolerant Wistar rats for 3 weeks. Blood glucose levels were measured weekly by Oral Glucose Tolerance Test. Pancreatic function was evaluated by plasma lipase of treated and non-treated glucose-tolerant and- intolerant rats after the 3-week treatment period. After 2 weeks oral treatment with Coreopsis tinctoria AcOEt fraction the animals were no longer glucose-intolerant, an effect maintained over the remaining experimental period. Additionally, plasma lipase values of glucose-intolerant animals treated with the AcOEt fraction (13.5 ± 0.84 U/L) showed a clear reduction when compared with the glucose-intolerant group (34.60 ± 1.76 U/L; P<0.001) and normoglycaemic control

Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans

DEFF Research Database (Denmark)

Howlett, K.; Galbo, Henrik; Lorentsen, J.

1999-01-01

for 45 min at 68 +/- 1 % maximum pulmonary O2 uptake (VO2,max), followed by 15 min at 84 +/- 2 % VO2, max without (-ADR) or with (+ADR) adrenaline infusion, which elevated plasma adrenaline levels (45 min, 4.49 +/- 0.69 nmol l-1; 60 min, 12.41 +/- 1.80 nmol l-1; means +/- s.e.m.). Glucose kinetics were...... measured using [3-3H]glucose. 3. Euglycaemia was maintained during exercise in CON and -ADR, whilst in +ADR plasma glucose was elevated. The exercise-induced increase in hepatic glucose production was similar in +ADR and -ADR; however, adrenaline infusion augmented the rise in hepatic glucose production...... early in exercise. Glucose uptake increased during exercise in +ADR and -ADR, but was lower and metabolic clearance rate was reduced in +ADR. 4. During exercise noradrenaline and glucagon concentrations increased, and insulin and cortisol concentrations decreased, but plasma levels were similar between...

The effect of a pre-anesthetic infusion of amino acids on body temperature, venous blood pH, glucose, creatinine, and lactate of healthy dogs during anesthesia.

Science.gov (United States)

Clark-Price, Stuart C; Dossin, Olivier; Ngwenyama, Thandeka R; O'Brien, Mauria A; McMichael, Maureen; Schaeffer, David J

2015-05-01

To evaluate the effect of preanesthetic, intravenous (IV) amino acids on body temperature of anesthetized healthy dogs. Randomized, experimental, crossover study. Eight mixed-breed dogs approximately 2 years of age weighing 20.7 ± 2.1 kg. Dogs received 10% amino acid solution (AA) or 0.9% saline (SA) IV at 5 mL kg(-1) over 60 minutes. Body temperature (BT) was recorded at 5 minute intervals during infusions. Dogs were then anesthetized with sevoflurane for 90 minutes. BT was recorded at 5 minute intervals during anesthesia. Jugular blood samples were analyzed for pH, glucose, creatinine, and lactate concentrations at baseline, after infusion, after anesthesia and after 24 hours. BT at conclusion of infusion decreased -0.34 ± 0.42 °C in group AA and -0.40 ± 0.38 °C in group SA and was not different between groups (p = 0.072). BT decreased 2.72 ± 0.37 °C in group AA and 2.88 ± 0.26 °C in group SA after anesthesia and was different between groups (p dogs, preanesthetic IV infusion of amino acids attenuated heat loss compared to controls, however, the amount attenuated may not be clinically useful. Further studies are warranted to determine if nutrient-induced thermogenesis is beneficial to dogs undergoing anesthesia. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Fasting and feeding variations of insulin requirements and insulin binding to erythrocytes at different times of the day in insulin dependent diabetics--assessed under the condition of glucose-controlled insulin infusion.

Science.gov (United States)

Hung, C T; Beyer, J; Schulz, G

1986-07-01

Nine insulin-dependent diabetic patients were examined for insulin requirement, counterregulatory hormones, and receptor binding during their connection to glucose-controlled insulin infusion system. They were of 103% ideal body weight. A diet of 45% carbohydrate, 20% protein and 35% fat was divided into three meals and three snacks averaging the daily calorie intake of 1859 kcal. Following an equilibrating phase of 14 hours after the connection to the glucose-controlled insulin infusion system the blood samples were taken at 0800, 1200 and 1800. The insulin infusion rate increased at 0300 in the early morning from 0.128 mU/kg/min to 0.221 mU/kg/min (P less than 0.02). The postprandial insulin infusion rate jumped from 0.7 U/h (0700-0800) to 7.5 U/h (0800-0900). The calorie related and carbohydrate related insulin demands after breakfast were also highest and declined after lunch respectively (1.16 uU/kg/min kj vs. 0.61 uU/kg/min kj, P less than 0.05 and 236 mU/g CHO vs. 129 mU/g CHO and 143 mU/g CHO). Of the counterregulatory hormones the cortisol showed a significant diurnal rhythm to insulin demands. The insulin tracer binding was higher at 0800 before breakfast than that at 1200 before lunch (P less than 0.05). The increased binding could be better attributed to receptor concentration change than to affinity change. The cause of insulin relative insensitivity in the morning could be due to altered liver response to the cortisol peak in type 1 diabetics. The preserved variation of insulin binding in our patients might be referred to feeding.

Moderate glucose supply reduces hemolysis during systemic inflammation

Directory of Open Access Journals (Sweden)

Jägers J

2018-03-01

Full Text Available Johannes Jägers,1 Stephan Brauckmann,2 Michael Kirsch,1 Katharina Effenberger-Neidnicht1,3 1Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany; 2Clinic for Anesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; 3Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany Background: Systemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation.Materials and methods: Systemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS infusion (1 mg LPS/kg and h, 300 min. Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h or excessively (210 mg glucose/kg and h during systemic inflammation. Vital parameters (eg, systemic blood pressure as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase were measured hourly. Clot formation was analyzed by thromboelastometry.Results: Continuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia, changes in hemodynamics (tachycardia and hypertension, and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation. It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase, alterations in blood coagulation (disturbed clot formation, and massive hemolysis. Both moderate and excessive glucose supply reduced LPS

PERAMALAN PERSEDIAAN INFUS MENGGUNAKAN METODE AUTOREGRESSIVE INTEGRATED MOVING AVERAGE (ARIMA) PADA RUMAH SAKIT UMUM PUSAT SANGLAH

OpenAIRE

I PUTU YUDI PRABHADIKA; NI KETUT TARI TASTRAWATI; LUH PUTU IDA HARINI

2018-01-01

Infusion supplies are an important thing that must be considered by the hospital in meeting the needs of patients. This study aims to predict the need for infusion of 0.9% 500 ml of NaCl and 5% 500 ml glucose infusion at Sanglah General Hospital (RSUP) Sanglah so that the hospital can estimate the many infusions needed for the next six months. The forecasting method used in this research is the autoregressive integrated moving average (ARIMA) time series method. The results of this study indi...

Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

Science.gov (United States)

Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

2015-08-01

To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

Effect of Insulin Infusion on insulin-like growth factor I (IGF-I) during Hemodialysis

DEFF Research Database (Denmark)

Reinhard, Mark; Frystyk, Jan; Bjerre, Mette

2012-01-01

Background: Hemodialysis (HD) is a catabolic procedure probably contributing to the high frequency of protein-energy wasting among patients on maintenance HD. The aim was to investigate the effect of insulin infusion on insulin-like growth factor I (IGF-I) during HD compared with a meal alone...... infusion and followed by the only meal allowed during the study. Results: Data are presented as mean±SD. From baseline to end of HD session we observed an overall increase in both serum bioactive IGF-I (from 0.83±0.27 to 1.01±0.34 µg/L, p... in the change between the groups (p=0.43). Conclusion: A meal at the beginning of a HD session leads to an increase in bioactive IGF-I thereby assumingly counteracting the catabolic effects of HD. However, according to changes in bioactive IGF-I neither glucose nor glucose-insulin infusion during HD appear...

Catecholamine stimulation, substrate competition, and myocardial glucose uptake in conscious dogs assessed with positron emission tomography

International Nuclear Information System (INIS)

Merhige, M.E.; Ekas, R.; Mossberg, K.; Taegtmeyer, H.; Gould, K.L.

1987-01-01

Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2- 18 F]-2-deoxyglucose (FDG) and 82 Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82 Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition

Increased basal glucose production in type 1 Gaucher's disease

NARCIS (Netherlands)

Corssmit, E. P.; Hollak, C. E.; Endert, E.; van Oers, M. H.; Sauerwein, H. P.; Romijn, J. A.

1995-01-01

To evaluate the metabolic effects of Gaucher's disease, glucose metabolism and parameters of fat metabolism were studied by indirect calorimetry and primed continuous infusion of [3-3H]glucose in seven clinically stable untreated patients with type 1 Gaucher's disease and in seven healthy matched

Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

Science.gov (United States)

Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

2017-07-01

Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

Starfruit Leaves as Glucose Absorption Inhibitor in Mice’s Small Intestinal Epithelial Cells

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Rifqi Y Muhammad

2016-12-01

Full Text Available Background: Starfruit (Averrhoa carambola leaves contain flavone derivatives that exhibit anti-hyperglycemic effects. This study aims to determine the effect of starfruit leaves in reducing glucose absorption in intestinal epithelial cells of mice. Methods: This study was done by performing perfusion on the small intestines of mice. The mice that were used in this study were divided into four groups. The control group was given glucose solution without infused starfruit leaves whereas, the remaining 3 groups were given 3 mmol (540 mg/dL glucose solution with infused starfruit leaves of varying concentrations; 200, 400, and 600 mg/kg. Samples were collected at 0, 15th, 30th, 45th, and 60th minute. The sample was tested for glucose levels using spectrophotometry. Results: Test of significance showed a significant difference between the control group and the test group with p < 0.05. Conclusions: Starfruit leaves have a reduction effect towards glucose absorption in the small intestines in Wistar strains where the group using 600 mg/kg of infused starfruit leaves have the most significant effect as compared to other groups.

Alterations in glucose kinetics induced by pentobarbital anesthesia

International Nuclear Information System (INIS)

Lang, C.H.; Bagby, G.J.; Hargrove, D.M.; Hyde, P.M.; Spitzer, J.J.

1987-01-01

Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%). Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia

Effects of hyperglycemia on glucose production and utilization in humans. Measurement with [3H]-2-, [3H]-3-, and [14C]-6-glucose

International Nuclear Information System (INIS)

Bell, P.M.; Firth, R.G.; Rizza, R.A.

1986-01-01

Studies with tritiated isotopes of glucose have demonstrated that hyperglycemia per se stimulates glucose utilization and suppresses glucose production in humans. These conclusions rely on the assumption that tritiated glucose provides an accurate measure of glucose turnover. However, if in the presence of hyperglycemia the isotope either loses its label during futile cycling or retains its label during cycling through glycogen, then this assumption is not valid. To examine this question, glucose utilization and glucose production rates were measured in nine normal subjects with a simultaneous infusion of [ 3 H]-2-glucose, an isotope that may undergo futile cycling but does not cycle through glycogen; [ 14 C]-6-glucose, an isotope that may cycle through glycogen but does not futile cycle; and [ 3 H]-3-glucose, an isotope that can both undergo futile cycling and cycle through glycogen. In the postabsorptive state at plasma glucose concentration of 95 mg X dl-1, glucose turnover determined with [ 14 C]-6-glucose (2.3 +/- 0.1 mg X kg-1 X min-1) was greater than that determined with [3 3 H]glucose (2.1 +/- 0.1 mg X kg-1 X min-1, P = 0.002) and slightly less than that determined with [ 3 H]-2-glucose (2.7 +/- 0.2 mg X kg-1 X min-1, P = 0.08). Plasma glucose was then raised from 95 to 135 to 175 mg X dl-1 while insulin secretion was inhibited, and circulating insulin, glucagon, and growth hormone concentrations were maintained constant by infusion of these hormones and somatostatin. Glucose production and utilization rates determined with [ 14 C]-6-glucose continued to be less than those determined with [ 3 H]-2-glucose and greater than those seen with [ 3 H]-3-glucose

Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

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Zukerman, Steven; Ackroff, Karen

2014-01-01

Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

International Nuclear Information System (INIS)

Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S.

1990-01-01

We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

The influence of GLP-1 on glucose-stimulated insulin secretion

DEFF Research Database (Denmark)

Kjems, Lise L; Holst, Jens Juul; Vølund, Aage

2003-01-01

. However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2...

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

The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

DEFF Research Database (Denmark)

Knudsen, Sine H; Karstoft, Kristian; Pedersen, Bente K

2014-01-01

We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty-four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age......: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m(2), P > 0.05) underwent a 180-min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6-(2)H2]glucose and ingestion of [U-(13)C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials......OGTT, and Rd (all P value in NGT subjects when compared to IGT and T2D subjects. Accordingly, following exercise, the plasma glucose concentration during the OGTT was increased in NGT subjects (P

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

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Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Superior Glycemic Control with a Glucose-Responsive Insulin Analog: Hepatic and Nonhepatic Impacts.

Science.gov (United States)

Moore, Mary Courtney; Kelley, David E; Camacho, Raul C; Zafian, Peter; Ye, Tian; Lin, Songnian; Kaarsholm, Niels C; Nargund, Ravi; Kelly, Terri M; Van Heek, Margaret; Previs, Stephen F; Moyes, Christopher; Smith, Marta S; Farmer, Ben; Williams, Phil; Cherrington, Alan D

2018-03-14

We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3- 3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2). Whole body insulin clearance (WBIC) and insulin concentrations were not different in P1 vs P2 with HI, but WBIC was 23% higher and arterial insulin 16% lower in P1 vs P2 with GRI. Net hepatic glucose output was similar between treatments in P1. In P2, both treatments induced net hepatic glucose uptake (2.1±0.5 [HI] vs 3.3±0.4 [GRI] mg/kg/min). Nonhepatic glucose uptake (nonHGU, mg/kg/min) in P1 and P2, respectively, differed between treatments (2.6±0.3 and 7.4±0.6 with HI; 2.0±0.2 and 8.1±0.8 with GRI). Thus, glycemia impacted GRI but not HI clearance, with resultant differential effects on HGU and nonHGU. GRI holds promise for decreasing hypoglycemia risk while enhancing glucose uptake under hyperglycemic conditions. © 2018 by the American Diabetes Association.

Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers.

Science.gov (United States)

Ullrich, Sina S; Fitzgerald, Penelope Ce; Schober, Gudrun; Steinert, Robert E; Horowitz, Michael; Feinle-Bisset, Christine

2016-11-01

The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake. In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying ( 13 C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P blood glucose AUC and peak blood glucose (P blood glucose AUC. Isoleucine did not affect energy intake. In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628. © 2016 American Society for Nutrition.

Effect of Intravenous Infusion Solutions on Bioelectrical Impedance Spectroscopy.

Science.gov (United States)

Yap, Jason; Rafii, Mahroukh; Azcue, Maria; Pencharz, Paul

2017-05-01

Bioelectrical impedance (BIA) is often used to measure body fluid spaces and thereby body composition. However, in acute animal studies, we found that impedance was driven by the saline content of intravenous (IV) fluids and not by the volume. The aim of the study was to investigate the effect of 3 different fluids acutely administered on the change in impedance, specifically resistance (R). Nine healthy adults participated in 3 treatment (0.9% saline, 5% dextrose, and a mixture of 0.3% saline + 3.3% dextrose) experiments on nonconsecutive days. They all received 1 L of one of the treatments intravenously over a 1-hour period. Repeated BIA measurements were performed prior to IV infusion and then every 5 minutes for the 1-hour infusion period, plus 3 more measurements up to 15 minutes after the completion of the infusion. The change in R in the 0.9% saline infusion experiment was significantly lower than that of the glucose and mixture treatment ( P < .001). Bioelectrical impedance spectroscopy and BIA measure salt rather than the volume changes over the infusion period. Hence, in patients receiving IV fluids, BIA of any kind (single frequency or multifrequency) cannot be used to measure body fluid spaces or body composition.

Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance.

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Songyan Wang

Full Text Available We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP on insulin secretion rates (ISRs and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.

Glutamate metabolism in temporal lobe epilepsy as revealed by dynamic proton MRS following the infusion of [U13-C] glucose.

Science.gov (United States)

Bartnik-Olson, Brenda L; Ding, Daniel; Howe, John; Shah, Amul; Losey, Travis

2017-10-01

Focal metabolic dysfunction commonly observed in temporal lobe epilepsy (TLE), and is associated with the development of medical intractability and neurocognitive deficits. It has not been established if this dysfunction is due to cell loss or biochemical dysfunction in metabolic pathways. To explore this question, dynamic 1 H MRS following an infusion of [U 13 - C] glucose was performed to measure glutamate (Glu) metabolism. Subjects (n=6) showed reduced Glu levels (ptemporal lobe (MTL) compared with controls (n=4). However, the rate of 13 C incorporation into Glu did not differ between those with epilepsy and controls (p=0.77). This suggests that reduced Glu concentrations in the region of the seizure focus are not due to disruptions in metabolic pathways, but may instead be due to neuronal loss or simplification. Copyright © 2017 Elsevier B.V. All rights reserved.

Duodenal mucosal protein kinase C-δ regulates glucose production in rats.

Science.gov (United States)

Kokorovic, Andrea; Cheung, Grace W C; Breen, Danna M; Chari, Madhu; Lam, Carol K L; Lam, Tony K T

2011-11-01

Activation of protein kinase C (PKC) enzymes in liver and brain alters hepatic glucose metabolism, but little is known about their role in glucose regulation in the gastrointestinal tract. We investigated whether activation of PKC-δ in the duodenum is sufficient and necessary for duodenal nutrient sensing and regulates hepatic glucose production through a neuronal network in rats. In rats, we inhibited duodenal PKC and evaluated whether nutrient-sensing mechanisms, activated by refeeding, have disruptions in glucose regulation. We then performed gain- and loss-of-function pharmacologic and molecular experiments to target duodenal PKC-δ; we evaluated the impact on glucose production regulation during the pancreatic clamping, while basal levels of insulin were maintained. PKC-δ was detected in the mucosal layer of the duodenum; intraduodenal infusion of PKC inhibitors disrupted glucose homeostasis during refeeding, indicating that duodenal activation of PKC-δ is necessary and sufficient to regulate glucose homeostasis. Intraduodenal infusion of the PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) specifically activated duodenal mucosal PKC-δ and a gut-brain-liver neuronal pathway to reduce glucose production. Molecular and pharmacologic inhibition of duodenal mucosal PKC-δ negated the ability of duodenal OAG and lipids to reduce glucose production. In the duodenal mucosa, PKC-δ regulates glucose homeostasis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Accuracy of Capillary and Arterial Whole Blood Glucose Measurements Using a Glucose Meter in Patients under General Anesthesia in the Operating Room.

Science.gov (United States)

Karon, Brad S; Donato, Leslie J; Larsen, Chelsie M; Siebenaler, Lindsay K; Wells, Amy E; Wood-Wentz, Christina M; Shirk-Marienau, Mary E; Curry, Timothy B

2017-09-01

The aim of this study was to evaluate the use of a glucose meter with surgical patients under general anesthesia in the operating room. Glucose measurements were performed intraoperatively on 368 paired capillary and arterial whole blood samples using a Nova StatStrip (Nova Biomedical, USA) glucose meter and compared with 368 reference arterial whole blood glucose measurements by blood gas analyzer in 196 patients. Primary outcomes were median bias (meter minus reference), percentage of glucose meter samples meeting accuracy criteria for subcutaneous insulin dosing as defined by Parkes error grid analysis for type 1 diabetes mellitus, and accuracy criteria for intravenous insulin infusion as defined by Clinical and Laboratory Standards Institute guidelines. Time under anesthesia, patient position, diabetes status, and other variables were studied to determine whether any affected glucose meter bias. Median bias (interquartile range) was -4 mg/dl (-9 to 0 mg/dl), which did not differ from median arterial meter bias of -5 mg/dl (-9 to -1 mg/dl; P = 0.32). All of the capillary and arterial glucose meter values met acceptability criteria for subcutaneous insulin dosing, whereas only 89% (327 of 368) of capillary and 93% (344 of 368) arterial glucose meter values met accuracy criteria for intravenous insulin infusion. Time, patient position, and diabetes status were not associated with meter bias. Capillary and arterial blood glucose measured using the glucose meter are acceptable for intraoperative subcutaneous insulin dosing. Whole blood glucose on the meter did not meet accuracy guidelines established specifically for more intensive (e.g., intravenous insulin) glycemic control in the acute care environment.

Central effects of beta-endorphins on glucose homeostasis in the conscious dog

International Nuclear Information System (INIS)

Radosevich, P.M.; Lacy, D.B.; Brown, L.L.; Williams, P.E.; Abumrad, N.N.

1989-01-01

The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide

Central effects of beta-endorphins on glucose homeostasis in the conscious dog

Energy Technology Data Exchange (ETDEWEB)

Radosevich, P.M.; Lacy, D.B.; Brown, L.L.; Williams, P.E.; Abumrad, N.N.

1989-02-01

The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide.

Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via central nervous system ghrelin receptors.

Science.gov (United States)

Heppner, Kristy M; Piechowski, Carolin L; Müller, Anne; Ottaway, Nickki; Sisley, Stephanie; Smiley, David L; Habegger, Kirk M; Pfluger, Paul T; Dimarchi, Richard; Biebermann, Heike; Tschöp, Matthias H; Sandoval, Darleen A; Perez-Tilve, Diego

2014-01-01

Growth hormone secretagogue receptors (GHSRs) in the central nervous system (CNS) mediate hyperphagia and adiposity induced by acyl ghrelin (AG). Evidence suggests that des-AG (dAG) has biological activity through GHSR-independent mechanisms. We combined in vitro and in vivo approaches to test possible GHSR-mediated biological activity of dAG. Both AG (100 nmol/L) and dAG (100 nmol/L) significantly increased inositol triphosphate formation in human embryonic kidney-293 cells transfected with human GHSR. As expected, intracerebroventricular infusion of AG in mice increased fat mass (FM), in comparison with the saline-infused controls. Intracerebroventricular dAG also increased FM at the highest dose tested (5 nmol/day). Chronic intracerebroventricular infusion of AG or dAG increased glucose-stimulated insulin secretion (GSIS). Subcutaneously infused AG regulated FM and GSIS in comparison with saline-infused control mice, whereas dAG failed to regulate these parameters even with doses that were efficacious when delivered intracerebroventricularly. Furthermore, intracerebroventricular dAG failed to regulate FM and induce hyperinsulinemia in GHSR-deficient (Ghsr(-/-)) mice. In addition, a hyperinsulinemic-euglycemic clamp suggests that intracerebroventricular dAG impairs glucose clearance without affecting endogenous glucose production. Together, these data demonstrate that dAG is an agonist of GHSR and regulates body adiposity and peripheral glucose metabolism through a CNS GHSR-dependent mechanism.

Role of nitric oxide in glucose-, fructose and galactose-induced ...

African Journals Online (AJOL)

Previous studies have shown that the infusion of glucose, fructose and galactose resulted in significant increases in intestinal glucose uptake (IGU) and the role of nitric oxide in these responses was not known. The present study was designed to investigate the role of nitric oxide in the observed increases in IGU.

Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

Science.gov (United States)

Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

1995-11-01

Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

Bihormonal control of blood glucose in people with type 1 diabetes

DEFF Research Database (Denmark)

Batora, Vladimir; Tárnik, Marían; Murgaš, Ján

2015-01-01

-based activation of glucagon administration. The control algorithm consists of a Kalman filter, an insulin infusion model predictive controller (MPC), a proportional-derivative (PD) controller for glucagon infusion, and a meal time insulin bolus calculator. The PD controller is activated if the Kalman filter...... predicts hypoglycemia. Predictions utilize an ARMAX model describing glucose-insulin and glucose-glucagon dynamics. The model parameters are estimated from basic patient-specific data. A continuous glucose monitor provides feedback. We test the control algorithm using a simulation model with time......-varying parameters available for 3 patients. We consider a simulation scenario where meals are estimated correctly as well as overestimated by 30%. The simulation results demonstrate that during normal operation, the controller only needs insulin and does not need glucagon. During unexpected events, such as insulin...

Overnight glucose control in people with type 1 diabetes

DEFF Research Database (Denmark)

Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

2018-01-01

This paper presents an individualized model predictive control (MPC) algorithm for overnight blood glucose stabilization in people with type 1 diabetes (T1D). The MPC formulation uses an asymmetric objective function that penalizes low glucose levels more heavily. We compute the model parameters...... algorithm uses frequent glucose measurements from a continuous glucose monitor (CGM) and its decisions are implemented by a continuous subcutaneous insulin infusion (CSII) pump. We provide guidelines for tuning the control algorithm and computing the Kalman gain in the linear state space model in innovation...

Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation.

Science.gov (United States)

Hoy, Andrew J; Brandon, Amanda E; Turner, Nigel; Watt, Matthew J; Bruce, Clinton R; Cooney, Gregory J; Kraegen, Edward W

2009-07-01

Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding, in vivo skeletal muscle glucose uptake (31%, P muscle diacylglyceride and ceramide content over the same time course. However, there was an increase in cumulative exposure to long-chain acyl-CoA (70%) with lipid infusion. Interestingly, although muscle pyruvate dehydrogenase kinase 4 protein content was decreased in hyperinsulinemic glycerol-infused rats, this decrease was blunted in muscle from hyperinsulinemic lipid-infused rats. Decreased pyruvate dehydrogenase complex activity was also observed in lipid- and insulin-infused animals (43%). Overall, these results suggest that acute reductions in muscle glucose metabolism in rats with hyperlipidemia and hyperinsulinemia are more likely a result of substrate competition than a significant early defect in insulin action or signaling.

Continuous Glucose Monitoring in the Cardiac ICU: Current Use and Future Directions.

Science.gov (United States)

Scrimgeour, Laura A; Potz, Brittany A; Sellke, Frank W; Abid, M Ruhul

2017-11-01

Perioperative glucose control is highly important, particularly for patients undergoing cardiac surgery. Variable glucose levels before, during and after cardiac surgery lead to increased post-operative complications and patient mortality. [1] Current methods for intensive monitoring and treating hyperglycemia in the Intensive Care Unit (ICU) usually involve hourly glucose monitoring and continuous intravenous insulin infusions. With the advent of more accurate subcutaneous glucose monitoring systems, the role of improved glucose control with newer systems deserves consideration for widespread adoption.

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects.

Science.gov (United States)

Gosmanov, Aidar R; Smiley, Dawn D; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E

2012-10-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, pdextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. Copyright © 2012 Elsevier Inc. All rights reserved.

Static output feedback ℋ ∞ control for a fractional-order glucose-insulin system

KAUST Repository

N’ Doye, Ibrahima; Voos, Holger; Darouach, Mohamed; Schneider, Jochen G.

2015-01-01

disturbance. Numerical simulations are carried out to illustrate our proposed results and show that the nonlinear fractional-order glucose-insulin systems are, at least, as stable as their integer-order counterpart in the presence of exogenous glucose infusion

Small intestinal glucose delivery affects the glucose-lowering effect of acute vildagliptin in type 2 diabetes

DEFF Research Database (Denmark)

Wu, T; Zhang, X; Trahair, LG

2016-01-01

of the DPP-4 inhibitor, vildagliptin (VILD), during intraduodenal (ID) glucose infusion at 2 different rates within the physiological range of gastric emptying, in type 2 diabetes. Participants and Design: A total of 16 diet-controlled type 2 diabetic patients were studied on 4 separate days in double...

Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

DEFF Research Database (Denmark)

Mikines, K J; Sonne, B; Richter, Erik

1985-01-01

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

Simultaneous measurement of glucose transport and utilization in the human brain

Science.gov (United States)

Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

DEFF Research Database (Denmark)

Højberg, P V; Vilsbøll, T; Rabøl, R

2008-01-01

of near-normalisation of the blood glucose level could improve insulin responses to GIP and GLP-1 in patients with type 2 diabetes. METHODS: Eight obese patients with type 2 diabetes with poor glycaemic control (HbA(1c) 8.6 +/- 1.3%), were investigated before and after 4 weeks of near......-normalisation of blood glucose (mean blood glucose 7.4 +/- 1.2 mmol/l) using insulin treatment. Before and after insulin treatment the participants underwent three hyperglycaemic clamps (15 mmol/l) with infusion of GLP-1, GIP or saline. Insulin responses were evaluated as the incremental area under the plasma C......-peptide curve. RESULTS: Before and after near-normalisation of blood glucose, the C-peptide responses did not differ during the early phase of insulin secretion (0-10 min). The late phase C-peptide response (10-120 min) increased during GIP infusion from 33.0 +/- 8.5 to 103.9 +/- 24.2 (nmol/l) x (110 min)(-1...

Ruminant Nutrition Symposium: Productivity, digestion, and health responses to hindgut acidosis in ruminants.

Science.gov (United States)

Gressley, T F; Hall, M B; Armentano, L E

2011-04-01

Microbial fermentation of carbohydrates in the hindgut of dairy cattle is responsible for 5 to 10% of total-tract carbohydrate digestion. When dietary, animal, or environmental factors contribute to abnormal, excessive flow of fermentable carbohydrates from the small intestine, hindgut acidosis can occur. Hindgut acidosis is characterized by increased rates of production of short-chain fatty acids including lactic acid, decreased digesta pH, and damage to gut epithelium as evidenced by the appearance of mucin casts in feces. Hindgut acidosis is more likely to occur in high-producing animals fed diets with relatively greater proportions of grains and lesser proportions of forage. In these animals, ruminal acidosis and poor selective retention of fermentable carbohydrates by the rumen will increase carbohydrate flow to the hindgut. In more severe situations, hindgut acidosis is characterized by an inflammatory response; the resulting breach of the barrier between animal and digesta may contribute to laminitis and other disorders. In a research setting, effects of increased hindgut fermentation have been evaluated using pulse-dose or continuous abomasal infusions of varying amounts of fermentable carbohydrates. Continuous small-dose abomasal infusions of 1 kg/d of pectin or fructans into lactating cows resulted in decreased diet digestibility and decreased milk fat percentage without affecting fecal pH or VFA concentrations. The decreased diet digestibility likely resulted from increased bulk in the digestive tract or from increased digesta passage rate, reducing exposure of the digesta to intestinal enzymes and epithelial absorptive surfaces. The same mechanism is proposed to explain the decreased milk fat percentage because only milk concentrations of long-chain fatty acids were decreased. Pulse-dose abomasal fructan infusions (1 g/kg of BW) into steers resulted in watery feces, decreased fecal pH, and increased fecal VFA concentrations, without causing an

Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects

DEFF Research Database (Denmark)

Vilsbøll, Tina; Krarup, Thure; Madsbad, Sten

2003-01-01

was to evaluate this. Eight healthy male volunteers (mean age: 23 (range 20-25) years; mean body mass index: 22.2 (range 19.3-25.4) kg/m2) participated in studies involving stepwise glucose clamping at fasting plasma glucose levels and at 6 and 7 mmol/l. Physiological amounts of either GIP (1.5 pmol/kg/min), GLP......-1(7-36)amide (0.33 pmol/kg/min) or saline were infused for three periods of 30 min at each glucose level, with 1 h "washout" between the infusions. On a separate day, a standard meal test (566 kcal) was performed. During the meal test, peak insulin concentrations were observed after 30 min...... and amounted to 223+/-27 pmol/l. Glucose+saline infusions induced only minor increases in insulin concentrations. GLP-1 and GIP infusions induced significant and similar increases at fasting glucose levels and at 6 mmol/l. At 7 mmol/l, further increases were seen, with GLP-1 effects exceeding those of GIP...

Methodologic Considerations for Quantitative 18F-FDG PET/CT Studies of Hepatic Glucose Metabolism in Healthy Subjects.

Science.gov (United States)

Trägårdh, Malene; Møller, Niels; Sørensen, Michael

2015-09-01

PET with the glucose analog (18)F-FDG is used to measure regional tissue metabolism of glucose. However, (18)F-FDG may have affinities different from those of glucose for plasma membrane transporters and intracellular enzymes; the lumped constant (LC) can be used to correct these differences kinetically. The aims of this study were to investigate the feasibility of measuring human hepatic glucose metabolism with dynamic (18)F-FDG PET/CT and to determine an operational LC for (18)F-FDG by comparison with (3)H-glucose measurements. Eight healthy human subjects were included. In all studies, (18)F-FDG and (3)H-glucose were mixed in saline and coadministered. A 60-min dynamic PET recording of the liver was performed for 180 min with blood sampling from catheters in a hepatic vein and a radial artery (concentrations of (18)F-FDG and (3)H-glucose in blood). Hepatic blood flow was determined by indocyanine green infusion. First, 3 subjects underwent studies comparing bolus administration and constant-infusion administration of tracers during hyperinsulinemic-euglycemic clamping. Next, 5 subjects underwent studies comparing fasting and hyperinsulinemic-euglycemic clamping with tracer infusions. Splanchnic extraction fractions of (18)F-FDG (E*) and (3)H-glucose (E) were calculated from concentrations in blood, and the LC was calculated as ln(1 - E*)/ln(1 - E). Volumes of interest were drawn in the liver tissue, and hepatic metabolic clearance of (18)F-FDG (mL of blood/100 mL of liver tissue/min) was estimated. For bolus versus infusion, E* values were always negative when (18)F-FDG was administered as a bolus and were always positive when it was administered as an infusion. For fasting versus clamping, E* values were positive in 4 of 5 studies during fasting and were always positive during clamping. Negative extraction fractions were ascribed to the tracer distribution in the large volume of distribution in the prehepatic splanchnic bed. The LC ranged from 0.43 to 2

D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

International Nuclear Information System (INIS)

Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V.

1990-01-01

We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects

Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients

DEFF Research Database (Denmark)

Laursen, Torben; Jørgensen, Jens Otto Lunde; Jakobsen, Grethe

1995-01-01

effects with constant and pulsatile GH delivery. This study was carried out to compare the metabolic effects of longer term continuous infusion vs. daily injections of GH. Thirteen GH-deficient patients were studied in a cross-over design. The patients were randomized to receive GH as a continuous sc...... infusion by means of a portable pump for 1 month and as daily sc injections (at 1900 h) for another month. An average daily GH dosage (+/- SEM) of 3.15 +/- 0.27 IU was administered during both periods. Steady state 24-h profiles of GH, IGF-I, IGF-binding proteins (IGFBPs), insulin, glucose, lipid.......35 (infusion); P infusion induced higher nighttime than daytime GH levels (P = 0.01), indicating a diurnal variation in the absorption or clearance of GH. Serum IGF-I levels (micrograms per L) were slightly higher (P infusion [312...

Glucagon infusion increases rate of purine synthesis de novo in rat liver

International Nuclear Information System (INIS)

Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

1987-01-01

Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

Effects of Vildagliptin and Metformin on Blood Pressure and Heart Rate Responses to Small Intestinal Glucose in Type 2 Diabetes.

Science.gov (United States)

Wu, Tongzhi; Trahair, Laurence G; Little, Tanya J; Bound, Michelle J; Zhang, Xiang; Wu, Hang; Sun, Zilin; Horowitz, Michael; Rayner, Christopher K; Jones, Karen L

2017-05-01

To evaluate effects of vildagliptin and metformin on blood pressure (BP) and heart rate (HR) responses to intraduodenal (ID) glucose in diet-controlled type 2 diabetes. Study A compared vildagliptin (50 mg) and placebo, given 60 min before a 120-min ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4) in 16 patients. Study B compared metformin (850 mg) and placebo, given 30 min before ID2 over 120 min in 9 patients. Systolic ( P = 0.002) and diastolic ( P vildagliptin compared with placebo, without interaction between vildagliptin and the glucose infusion rate. In contrast, HR was greater after metformin than placebo ( P Vildagliptin reduces BP and increases HR, whereas metformin increases HR without affecting BP during ID glucose infusion in type 2 diabetes. These distinct cardiovascular profiles during enteral nutrient exposure may have implications for postprandial hypotension. © 2017 by the American Diabetes Association.

Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

DEFF Research Database (Denmark)

Torekov, Signe Sørensen; Kipnes, M S; Harley, R E

2011-01-01

To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty

DEFF Research Database (Denmark)

Plamboeck, Astrid; Veedfald, Simon; Deacon, Carolyn F

2013-01-01

=16) and matched controls (n=10) underwent 50 g-oral glucose tolerance test (OGTT)±vildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i. RESULTS: Isoglycaemia was obtained with 25±2 g glucose in vagotomised subjects and 18±2 g in controls...

Glucose recovery after intranasal glucagon during hypoglycaemia in man

DEFF Research Database (Denmark)

Hvidberg, A; Djurup, R; Hilsted, J

1994-01-01

to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...... concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...

Effects of free fatty acids per se on glucose production, gluconeogenesis, and glycogenolysis

DEFF Research Database (Denmark)

Staehr, Peter; Hother-Nielsen, Ole; Landau, Bernard R

2003-01-01

Insulin-independent effects of a physiological increase in free fatty acid (FFA) levels on fasting glucose production, gluconeogenesis, and glycogenolysis were assessed by administering [6,6-(2)H(2)]-glucose and deuteriated water ((2)H(2)O) in 12 type 1 diabetic patients, during 6-h infusions...

13C NMR for the assessment of human brain glucose metabolism in vivo

International Nuclear Information System (INIS)

Beckman, N.; Seelig, J.; Turkalj, I.; Keller, U.

1991-01-01

Proton-decoupled 13 C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1- 13 C]glucose in normal volunteers. In addition to 13 C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1- 13 C]glucose, the signals of α- and β-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 minutes. The spatial localization of the different regions of interest was confirmed by 13 C NMR spectroscopic imaging with a time resolution of 9 minutes. Increasing the enrichment level to 99% [1- 13 C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1- 13 C]glucose. The time course of 13 C label incorporation into the C 2 , C 3 , and C 4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body

GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

2014-01-01

The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

First-pass metabolism of ethanol in human beings: effect of intravenous infusion of fructose

DEFF Research Database (Denmark)

Parlesak, Alexandr; Billinger, MH; Schäfer, C.

2004-01-01

Intravenous infusion of fructose has been shown to enhance reduced form of nicotinamide adenine dinucleotide reoxidation and, thereby, to enhance the metabolism of ethanol. In the current study, the effect of fructose infusion on first-pass metabolism of ethanol was studied in human volunteers....... A significantly higher first-pass metabolism of ethanol was obtained after administration of fructose in comparison with findings for control experiments with an equimolar dose of glucose. Because fructose is metabolized predominantly in the liver and can be presumed to have virtually no effects in the stomach...

Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat

International Nuclear Information System (INIS)

Flores, E.A.; Istfan, N.; Pomposelli, J.J.; Blackburn, G.L.; Bistrian, B.R.

1990-01-01

We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U- 14 C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection

Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men

International Nuclear Information System (INIS)

Clore, J.N.; Glickman, P.S.; Helm, S.T.; Nestler, J.E.; Blackard, W.G.

1991-01-01

The authors previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent [3-3H]glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 ± 1.1 at 2430 to 8.9 ± 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200. The fall in Ra was associated with decreases in FFA (0.57 ± 0.10 to 0.48 ± 0.07 mM) and glycerol (0.08 ± 0.01 to 0.06 ± 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 ± 0.21 and 0.11 ± 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 ± 0.07 to 0.95 ± 0.05 mM, P less than 0.01) stimulated gluconeogenesis ([U-14C]alanine to glucose) twofold (188 ± 22% increase compared to 114 ± 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 ± 0.5 vs. 10.7 ± 0.6 mumol.kg-1.min-1) during lipid infusion

Association between birth conditions and glucose and cortisol profiles of periparturient dairy cows and neonatal calves.

Science.gov (United States)

Vannucchi, C I; Rodrigues, J A; Silva, L C G; Lúcio, C F; Veiga, G A L; Furtado, P V; Oliveira, C A; Nichi, M

2015-04-04

Parturition in cattle is a stressful event for both the dam and the offspring. Stress and pain can alter the energy profile of calves and calving cows, producing a metabolic imbalance at birth. This study aimed to assess the effects of dystocia and oxytocin and calcium infusion on metabolic homeostasis in dairy cows and calves. Thirty Holstein cows and their calves were divided into three groups: an eutocia group (n=10), in which no calving assistance was needed; a dystocia group, which required mild-to-severe obstetric assistance (n=10); and a uterine inertia group, which was treated with oxytocin and calcium (n=10). To assess serum cortisol and blood glucose levels, blood samples were collected during the peripartum period from cows and during the first hour since birth from calves. All groups were hyperglycaemic following parturition. Infusion of oxytocin and calcium resulted in lower maternal glucose concentrations and lower levels of stress than in cows in the dystocia group. Birth condition was significantly associated with blood glucose and cortisol concentrations in calves. Glucose concentration was lower in calves born with oxytocin and calcium infusion than those born with fetal extraction. In conclusion, assisted calving with fetal extraction causes important metabolic changes for the dam and calf. Conversely, the practice of oxytocin and calcium infusion for hypotonic cows has no harmful effects on metabolic balance and can be safely employed as a medical treatment. British Veterinary Association.

Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

Directory of Open Access Journals (Sweden)

Jiming Chen

2008-03-01

Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

Direct analysis of [6,6-(2)H2]glucose and [U-(13)C6]glucose dry blood spot enrichments by LC-MS/MS.

Science.gov (United States)

Coelho, Margarida; Mendes, Vera M; Lima, Inês S; Martins, Fátima O; Fernandes, Ana B; Macedo, M Paula; Jones, John G; Manadas, Bruno

2016-06-01

A liquid chromatography tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring (MRM) in a triple-quadrupole scan mode was developed and comprehensively validated for the determination of [6,6-(2)H2]glucose and [U-(13)C6]glucose enrichments from dried blood spots (DBS) without prior derivatization. The method is demonstrated with dried blood spots obtained from rats administered with a primed-constant infusion of [U-(13)C6]glucose and an oral glucose load enriched with [6,6-(2)H2]glucose. The sensitivity is sufficient for analysis of the equivalent to blood and the overall method was accurate and precise for the determination of DBS isotopic enrichments. Copyright © 2016 Elsevier B.V. All rights reserved.

Infusion cisternography

International Nuclear Information System (INIS)

Magnaes, B.; Rootwelt, K.; Sjaastad, O.

1976-01-01

A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort

AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

Science.gov (United States)

de Laat, M A; Robinson, M A; Gruntmeir, K J; Liu, Y; Soma, L R; Lacombe, V A

2015-09-01

Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P managing IR requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

Science.gov (United States)

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Glucose Pump Test can be Used to Measure Blood Flow Rate of ...

African Journals Online (AJOL)

The aim of study is to determine whether glucose pump test (GPT) is used for surveillance of native AV fistulas by using Doppler US as reference. Methods: In 93 chronic hemodialysis patients with native AV fistula, blood flow rates were measured by Doppler US and GPT. For GPT, glucose was infused to 16 mL/min by ...

Níveis glicêmicos e de colesterol em ratos com Diabetes Mellitus aloxano induzido, tratados com infusão de Bauhinia candicans ou Syzygium Jambolanum Glucose and cholesterol plasma levels in rats with alloxan-induced Diabetes Mellitus treated with infusion of Bauhinia candicans or Syzygium Jambolanum

Directory of Open Access Journals (Sweden)

Julio Cesar Mendes Soares

2000-03-01

, respectively. Group 1 (C was the control group, receiving standard rodent feed and water ad libitum. Group 2 (TI received rodent feed and an infusion of Syzygium jambolanum ad libitum. Group 3 (TII received the feed and an infusion of Bauhinia candicans. Animals were treated for a period of 21 and 40 days for experiments I and II respectively. Blood was collected by retro orbital sinus puncture with animals under ether anesthesia on days 3, 9, 16, and 23 for experiment I; and days 3, 12, 24, and 40 for experiment II. At the end of both experiments, all animals were euthanized and liver and pancreas samples were collected for light microscopy. All animals, in both experiments, had blood glucose levels above 170mg% on the third day after last alloxan injection. In the first experiment, plasma glucose was lower (P < 0.001 in TI as compared to C on day 23. In experiment II, plasma glucose was lower in TI when compared to C on days 16 (P < 0.004 and 40 (P < 0.0001. Moreover, clinical signs of IDDM like polyfagya, polydpsya were attenuated in this group. Plasma cholesterol showed a slight increase in all animals in experiment II but no differences were observed between control and treated groups. Histopathological analysis of pancreas and liver samples in the first experiment did not show marked differences between C and treated groups. However, in experiment II, 9 out of 10 pancreas samples examined from C, and 5 out of 9 samples from TII presented necrosis. Meanwhile, only 2 out of 9 pancreas samples from TI showed islet necrosis. In conclusion, the results suggest that the use of an infusion of Syzygium jambolanum instead of water is efficient in the control of hyperglycemia and reduction of clinical signs associated with IDDM. On the other hand, the use of an infusion of Bauhinia candicans has no effect over theses variables.

Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency

NARCIS (Netherlands)

Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

Background: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate

The regulation of cerebral glucose uptake and metabolism in normal and diabetic man

International Nuclear Information System (INIS)

Polonsky, K.

1987-01-01

The effects of changes in serum insulin and glucose on brain glucose metabolism using PET technology were investigated. Eight normal, right-handed, male subjects were studied on three separate occasions at least one week apart. In each subject a PET scan was performed under three different metabolic circumstances: basal conditions after an overnight fast, euglycemic clamp, and hypoglycemic clamp in which the plasma glucose was maintained at 55 mg/dl. Exogenous insulin was infused at the same rate in the euglycemic and hypoglycemic clamp studies. In the latter study, the concomitant glucose infusion rate was reduced to allow the plasma glucose concentration to fall to the desired level of mild hypoglycemia. During each study, dynamic positron emission tomography was used to characterize cerebral uptake and distribution of the Fluorine-18 2-deoxyglucose radiotracer as a function of time. Analysis of the brain uptake curve and tracer input function provided rate constants for transport and phosphorylation in accord with a 3 compartmental model (Sokoloff, 1979). Dynamic scans were performed on each study occasion allowing individual rate constants to be studied. In addition to the brain uptake curves, plasma glucose, F-18 2DG levels and counterregulatory hormone values were determined from frequent arterialized venous blood samples

Glucose metabolism in lactating reindeer

Energy Technology Data Exchange (ETDEWEB)

White, R G; Luick, J R

1976-01-01

Changes in glucose synthesis during the lactation cycle were estimated in pen-fed and grazing reindeer. The pool size, space, transfer rate, and irreversible loss of glucose were determined using simultaneous injections of (2-/sup 3/H)glucose and primed infusions of (U-/sup 14/C)glucose in reindeer lactating for 1-2, 4-5, 8-9, and 12-16 weeks. Glucose transfer rate and irreversible loss were higher during early to midlactation than at other times of the year; maximum estimates were at 8-9 week postpartum (July), and a decline was noted at 12-16 weeks (August). During the first 1-2 weeks in pen-fed and 4-5 weeks in grazing reindeer, glucose transfer rate and irreversible loss were almost twice the values reported for reindeer at maintenance. No difference in the irreversible loss of glucose was noted between lactating and non-lactating reindeer at 18-20 weeks postpartum (September), and there is evidence that this may occur as early as 12-16 weeks postpartum. No significant trend was noted in the glucose space throughout lactation; however, a significant increase in plasma glucose concentration and pool size was noted when glucose synthesis was highest (8-9 weeks postpartum). Glucose turnover time was consistently faster (78-88 min) in lactating than in non-lactating reindeer (107-140 min). Reindeer used a smaller proportion of plasma glucose-C for lactose synthesis than did other domestic species. This probably results from the low lactose content of reindeer milk and the relatively low rate of milk secretion. (auth)

Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing.

Science.gov (United States)

Knauf, Claude; Cani, Patrice D; Kim, Dong-Hoon; Iglesias, Miguel A; Chabo, Chantal; Waget, Aurélie; Colom, André; Rastrelli, Sophie; Delzenne, Nathalie M; Drucker, Daniel J; Seeley, Randy J; Burcelin, Remy

2008-10-01

Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system. We selectively activated the axis in mice using a low-rate intragastric glucose infusion in wild-type and glucagon-like peptide-1 (GLP-1) receptor knockout mice, neuropeptide Y-and proopiomelanocortin-green fluorescent protein-expressing mice, and high-fat diet diabetic mice. We quantified the whole-body glucose utilization rate and the pattern of c-Fos positive in the brain. Enteric glucose increased muscle glycogen synthesis by 30% and regulates c-Fos expression in the brainstem and the hypothalamus. Moreover, the synthesis of muscle glycogen was diminished after central infusion of the GLP-1 receptor (GLP-1Rc) antagonist Exendin 9-39 and abolished in GLP-1Rc knockout mice. Gut-glucose-sensitive c-Fos-positive cells of the arcuate nucleus colocalized with neuropeptide Y-positive neurons but not with proopiomelanocortin-positive neurons. Furthermore, high-fat feeding prevented the enteric activation of c-Fos expression. We conclude that the gut-glucose sensor modulates peripheral glucose metabolism through a nutrient-sensitive mechanism, which requires brain GLP-1Rc signaling and is impaired during diabetes.

Infusion Extractor

Science.gov (United States)

Chang-Diaz, Franklin R.

1988-01-01

Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

Influence of prolonged starvation on glucose kinetics in pregnant patients infected with Plasmodium falciparum

NARCIS (Netherlands)

van Thien, Huynh; Ackermans, M. T.; Weverling, G. J.; Thanh Chien, V. O.; Endert, E.; Kager, P. A.; Sauerwein, H. P.

2004-01-01

Hypoglycaemia is a recognised complication of malaria in pregnancy, but its pathophysiology is not well understood. We studied the influence of fasting on glucose production and gluconeogenesis by infusion of [6,6-H-2(2)]glucose and ingestion of (H2O)-H-2 in 20 female subjects, eight pregnant

Small intestinal digestion of raw cornstarch in cattle consuming a soybean hull-based diet is improved by duodenal casein infusion.

Science.gov (United States)

Brake, D W; Titgemeyer, E C; Bailey, E A; Anderson, D E

2014-09-01

Six duodenally and ileally cannulated steers were used in 3 sequential studies to measure 1) basal nutrient flows from a soybean hull-based diet, 2) small intestinal digestibility of raw cornstarch continuously infused into the duodenum, and 3) responses of small intestinal starch digestion to duodenal infusion of 200 or 400 g/d casein. Our objective was to evaluate responses in small intestinal starch digestion in cattle over time and to measure responses in small intestinal starch digestion to increasing amounts of MP. On average, cattle consumed 3.7 kg/d DM, 68 g/d dietary N, and 70 g/d dietary starch. Starch flow to the duodenum was small (38 g/d), and N flow was 91 g/d. Small intestinal digestibility of duodenal N was 57%, and small intestinal digestion of duodenal starch flow was extensive (92%). Small intestinal starch digestibility was 34% when 1.5 kg/d raw cornstarch was continuously infused into the duodenum. Subsequently, cattle were placed in 1 of 2 replicated Latin squares that were balanced for carryover effects to determine response to casein infusions and time required for adaptation. Duodenal infusion of casein linearly increased (P ≤ 0.05) small intestinal starch digestibility, and small intestinal starch digestion adapted to infusion of casein in 6 d. Ethanol-soluble starch and unpolymerized glucose flowing to the ileum increased linearly (P ≤ 0.05) with increasing infusion of casein. Plasma cholecystokinin was not affected by casein infusion, but circulating levels of glucose were increased by casein supplementation (P ≤ 0.05). Responses in small intestinal starch digestion in cattle adapted to casein within 6 d, and increases in duodenal supply of casein up to 400 g/d increased small intestinal starch digestion in cattle.

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.

Erroneous glucose recordings while using mutant variant of quinoprotein glucose dehydrogenase glucometer in a child with galactosemia

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Vivek Mathew

2013-01-01

Full Text Available We report a 2-month-old child with galactosemia and falsely high glucose readings with a glucometer using mutant variant of quinoprotein glucose dehydrogenase (MutQ-GDH chemistry. Potentially fatal hypoglycemia could have been induced in the child if insulin infusion had been initiated as per glycemic management protocol. Even though, the product information with the glucometer carries warning regarding interference by high galactose levels, the awareness regarding this interaction is generally poor in many practice settings. Although, false readings have been reported with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ glucometers, to our knowledge this is the first case report of a falsely high glucose reading due to high galactose in a proven case of galactosemia with a glucometer using the MutQ-GDH chemistry (a modified GDH-PQQ chemistry. Our experience has prompted us to write this case report and we suggest avoiding these glucometers in neonates and infants when a metabolic disease is suspected.

Entry rates and recycling of glucose in buffalo calves fed on urea molasses liquid diet

International Nuclear Information System (INIS)

Varma, Arun; Singh, U.B.; Verma, D.N.; Ranjhan, S.K.

1974-01-01

Entry rates of glucose have been measured in buffalo calves by using a dual-isotope dilution method based on continuous infusion of (U- 14 C)D-glucose and (6- 3 H)D-glucose into the blood at a precise controlled rate for 540 min. After 5 h a plateau was obtained in the specific radioactivity of the plasma glucose from which glucose synthesis and entry rates were calculated. The average entry rates of glucose were 112 and 145 mg/min measured by 14 C and 3 H labelled glucose respectively. About 23 percent of the glucose carbon was recycled in the pool. The average recycling rate was 33 mg/min. (author)

Effects of Cr methionine on glucose metabolism, plasma metabolites, meat lipid peroxidation, and tissue chromium in Mahabadi goat kids.

Science.gov (United States)

Emami, A; Ganjkhanlou, M; Zali, A

2015-03-01

This study was designed to investigate the effects of chromium methionine (Cr-Met) on glucose metabolism, blood metabolites, meat lipid peroxidation, and tissue chromium (Cr) in Mahabadi goat kids. Thirty-two male kids (16.5 ± 2.8 kg BW, 4-5 months of age) were fed for 90 days in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 0.5, 1, and 1.5 mg Cr as Cr-Met/animal/daily. Blood samples were collected via heparin tubes from the jugular vein on 0, 21, 42, 63, and 90 days of experiment. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. At the end of the feeding trial, the kids were slaughtered, and the liver, kidney, and longissimus dorsi (LD) muscle samples were collected. Plasma glucose, insulin, and triglyceride concentrations were decreased by Cr supplementation (P glucose concentrations at 30 and 60 min after glucose infusion were lower in the kids fed 1.5 mg Cr diet than the kids fed control diet (P glucose clearance rate (K) and lower glucose half-life (T½; P Glucose area under the response curve (AUC) from 0 to 180 min after glucose infusion was decreased linearly (P glucose utilization and lipid oxidation of meat in fattening kid.

Estimation of glucose kinetics in fetal-maternal studies: Potential errors, solutions, and limitations

International Nuclear Information System (INIS)

Menon, R.K.; Bloch, C.A.; Sperling, M.A.

1990-01-01

We investigated whether errors occur in the estimation of ovine maternal-fetal glucose (Glc) kinetics using the isotope dilution technique when the Glc pool is rapidly expanded by exogenous (protocol A) or endogenous (protocol C) Glc entry and sought possible solutions (protocol B). In protocol A (n = 8), after attaining steady-state Glc specific activity (SA) by [U-14C]glucose (period 1), infusion of Glc (period 2) predictably decreased Glc SA, whereas. [U-14C]glucose concentration unexpectedly rose from 7,208 +/- 367 (means +/- SE) in period 1 to 8,558 +/- 308 disintegrations/min (dpm) per ml in period 2 (P less than 0.01). Fetal endogenous Glc production (EGP) was negligible during period 1 (0.44 +/- 1.0), but yielded a physiologically impossible negative value of -2.1 +/- 0.72 mg.kg-1.min-1 during period 2. When the fall in Glc SA during Glc infusion was prevented by addition of [U-14C]glucose admixed with the exogenous Glc (protocol B; n = 7), EGP was no longer negative. In protocol C (n = 6), sequential infusions of four increasing doses of epinephrine serially decreased SA, whereas tracer Glc increased from 7,483 +/- 608 to 11,525 +/- 992 dpm/ml plasma (P less than 0.05), imposing an obligatory underestimation of EGP. Thus a tracer mixing problem leads to erroneous estimations of fetal Glc utilization and Glc production via the three-compartment model in sheep when the Glc pool is expanded exogenously or endogenously. These errors can be minimized by maintaining the Glc SA relatively constant

A mathematical model describing the glycemic response of diabetic patients to meal and i.v. infusion of insulin.

Science.gov (United States)

Fabietti, P G; Calabrese, G; Iorio, M; Bistoni, S; Brunetti, P; Sarti, E; Benedetti, M M

2001-10-01

Nine type 1 diabetic patients were studied for 24 hours. During this period they were given three calibrated meals. The glycemia was feedback-controlled by means of an artificial pancreas. The blood concentration of glucose and the infusion speed of the insulin were measured every minute. The experimental data referring to each of the three meals were used to estimate the parameters of a mathematical model suitable for describing the glycemic response of diabetic patients at meals and at the i.v. infusion of exogenous insulin. From the estimate a marked dispersion of the parameters was found, both interindividual and intraindividual. Nevertheless the models thus obtained seem to be usable for the synthesis of a feedback controller, especially in view of creating a portable artificial pancreas that now seems possible owing to the realization (so far experimental) of sufficiently reliable glucose concentration sensors.

Entry rates and recycling of glucose in buffalo calves fed on urea molasses liquid diet

Energy Technology Data Exchange (ETDEWEB)

Varma, A; Singh, U B; Verma, D N; Ranjhan, S K [Indian Veterinary Research Inst., Izatnagar. Div. of Animal Nutrition

1974-12-01

Entry rates of glucose have been measured in buffalo calves by using a dual-isotope dilution method based on continuous infusion of (U-/sup 14/C)D-glucose and (6-/sup 3/H)D-glucose into the blood at a precise controlled rate for 540 min. After 5 h a plateau was obtained in the specific radioactivity of the plasma glucose from which glucose synthesis and entry rates were calculated. The average entry rates of glucose were 112 and 145 mg/min measured by /sup 14/C and /sup 3/H labelled glucose respectively. About 23 percent of the glucose carbon was recycled in the pool. The average recycling rate was 33 mg/min.

Role of liver nerves and adrenal medulla in glucose turnover of running rats

DEFF Research Database (Denmark)

Sonne, B; Mikines, K J; Richter, Erik

1985-01-01

Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats...

Triglyceride synthesis in epididymal adipose tissue: contribution of glucose and non-glucose carbon sources.

Science.gov (United States)

Bederman, Ilya R; Foy, Steven; Chandramouli, Visvanathan; Alexander, James C; Previs, Stephen F

2009-03-06

The obesity epidemic has generated interest in determining the contribution of various pathways to triglyceride synthesis, including an elucidation of the origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized that a dietary intervention would demonstrate the importance of using glucose versus non-glucose carbon sources to synthesize triglycerides in white adipose tissue. C57BL/6J mice were fed either a low fat, high carbohydrate (HC) diet or a high fat, carbohydrate-free (CF) diet and maintained on 2H2O (to determine total triglyceride dynamics) or infused with [6,6-(2)H]glucose (to quantify the contribution of glucose to triglyceride glycerol). The 2H2O labeling data demonstrate that although de novo lipogenesis contributed approximately 80% versus approximately 5% to the pool of triglyceride palmitate in HC- versus CF-fed mice, the epididymal adipose tissue synthesized approximately 1.5-fold more triglyceride in CF- versus HC-fed mice, i.e. 37+/-5 versus 25+/-3 micromolxday(-1). The [6,6-(2)H]glucose labeling data demonstrate that approximately 69 and approximately 28% of triglyceride glycerol is synthesized from glucose in HC- versus CF-fed mice, respectively. Although these data are consistent with the notion that non-glucose carbon sources (e.g. glyceroneogenesis) can make substantial contributions to the synthesis of triglyceride glycerol (i.e. the absolute synthesis of triglyceride glycerol from non-glucose substrates increased from approximately 8 to approximately 26 micromolxday(-1) in HC- versus CF-fed mice), these observations suggest (i) the importance of nutritional status in affecting flux rates and (ii) the operation of a glycerol-glucose cycle.

Fuels derived from starch digestion have different effects on energy intake and metabolic responses of cows in the postpartum period.

Science.gov (United States)

Gualdrón-Duarte, Laura B; Allen, Michael S

2018-03-07

Absorbed fuels from the digestion of starch include propionic acid (PA) produced by ruminal fermentation and glucose (GLU) from intestinal digestion, which may be partially metabolized to lactic acid (LA) by intestinal tissues. Our objective was to evaluate the effects of these fuels on dry matter intake (DMI) and feeding behavior of cows in the postpartum period. We hypothesized that these fuels affect feed intake differently and that their effects are related to differences in their hepatic metabolism. Glucose was expected to have little effect on feed intake because little or no GLU is extracted from the blood by the liver. Whereas both LA and PA are anaplerotic and can stimulate oxidation of acetyl CoA in hepatocytes, hepatic extraction of PA is greater than LA, which depends on cytosolic redox state. Continuous isoenergetic infusions (150 kcal of ME/h) of PA, LA, or GLU or no infusion were administered abomasally to 8 ruminally cannulated multiparous Holstein cows (12.4 ± 6.2 d postpartum) in a duplicate 4 × 4 Latin square design experiment, with four 1-d infusion periods, balanced for carry-over effects. Treatment sequences were assigned to cows randomly, and treatments included control (CON, no infusion), PA (0.41 mol/h), LA (0.46 mol/h), and GLU (0.22 mol/h). Solutions containing treatments were infused at 500 mL/h for 22 h/d and provided ~3.3 Mcal/d. Feeding behavior was recorded by a computerized data acquisition system. Gross energy digestibility of the diet was determined for each cow and used to calculate metabolizable energy intake (MEI) from the diet. Total MEI was calculated as the sum of MEI from the diet plus energy from infusions. Data were analyzed statistically with a mixed model including the fixed effect of treatment and random effects of block and cow within block. Each treatment was compared with CON by contrasts. Compared with CON, PA decreased DMI by 24% (14.3 vs. 18.9 kg/d) and total MEI by 13% (34.8 vs. 40.2 Mcal/d) with a tendency to

Efficacy and safety of an insulin infusion protocol in a surgical ICU.

Science.gov (United States)

Taylor, Beth E; Schallom, Marilyn E; Sona, Carrie S; Buchman, Timothy G; Boyle, Walter A; Mazuski, John E; Schuerer, Douglas E; Thomas, James M; Kaiser, Christy; Huey, Way Y; Ward, Myrna R; Zack, Jeanne E; Coopersmith, Craig M

2006-01-01

Hyperglycemia is associated with complications in the surgical intensive care unit. The purpose of this study was to determine the efficacy and safety of nurse-driven insulin infusion protocols in lowering blood glucose (BG) in critical illness. All patients in a 24-bed surgical intensive care unit who required i.v. insulin infusions during 3 noncontiguous 6-month periods from 2002 to 2004 were evaluated. In the preintervention phase, 71 patients received a physician-initiated insulin infusion without a developed protocol. They were compared with 95 patients who received a nurse-driven insulin infusion protocol with a target BG of 120 to 150 mg/dL and to 119 patients who received a more stringent protocol with a target BG of 80 to 110 mg/dL. There was a stepwise decrease in average daily BG levels, from 190 to 163 to 132 mg/dL (p < 0.001). The less stringent protocol decreased the time to achieve a BG level < 150 mg/dL from 14.1 to 7.4 hours compared with physician-driven management (p < 0.05) resulting in similar time on an insulin infusion (53 versus 48 hours). The more intensive protocol brought BG levels < 150 mg/dL in 7.2 hours and < 111 mg/dL in 13.6 hours, but increased the length of time a patient was on an insulin infusion to 77 hours. The incidence of severe hypoglycemia (BG < 40 mg/dL) was statistically similar between the groups, ranging between 1.1% and 3.4%. Implementation of a nurse-driven protocol led to more rapid and more effective BG control in critically ill surgical patients compared with physician management. Tighter BG control can be obtained without a significant increase in hypoglycemia, although this is associated with increased time on an insulin infusion.

Glucose kinetics in infants of diabetic mothers

International Nuclear Information System (INIS)

Cowett, R.M.; Susa, J.B.; Giletti, B.; Oh, W.; Schwartz, R.

1983-01-01

Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-[U-13C] glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia

Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes

DEFF Research Database (Denmark)

Nauck, Michael A; El-Ouaghlidi, Andrea; Gabrys, Bartholomäus

2004-01-01

) and an "isoglycaemic" intravenous glucose infusion. Blood was drawn over 240 min for plasma glucose (glucose oxidase), insulin, C-peptide, GIP and glucagon-like peptide 1 (GLP-1; specific immunoassays). RESULTS: The pattern of glucose concentrations could precisely be copied by the intravenous glucose infusion (p=0......AIMS/HYPOTHESIS: Since insulin secretion in response to exogenous gastric inhibitory polypeptide (GIP) is diminished not only in patients with type 2 diabetes, but also in their normal glucose-tolerant first-degree relatives, it was the aim to investigate the integrity of the entero-insular axis...... in such subjects. METHODS: Sixteen first-degree relatives of patients with type 2 diabetes (4 male, 12 female, age 50+/-12 years, BMI 26.1+/-3.8 kg/m(2)) and 10 matched healthy controls (negative family history, 6 male, 4 female, 45+/-13 years, 26.1+/-4.2 kg/m(2)) were examined with an oral glucose load (75 g...

Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure

DEFF Research Database (Denmark)

Halbirk, Mads; Nørrelund, Helene; Møller, Niels

2010-01-01

effects of 48-h GLP-1 infusions in patients with congestive HF. In a randomized, double-blind crossover design, 20 patients without diabetes and with HF with ischemic heart disease, EF of 30 +/- 2%, New York Heart Association II and III (n = 14 and 6) received 48-h GLP-1 (0.7 pmol.kg(-1).min(-1......)) and placebo infusion. At 0 and 48 h, LVEF, diastolic function, tissue Doppler regional myocardial function, exercise testing, noninvasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Fifteen patients completed...... patients. GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in patients without diabetes but with compensated HF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires...

Fatores de risco, achados clínicos, laboratoriais e avaliação terapêutica em 36 bovinos com deslocamento de abomaso Risk factors, clinical and laboratorial findings and therapeutic evaluation in 36 cattle with abomasal displacement

Directory of Open Access Journals (Sweden)

Antônio Carlos Lopes Câmara

2010-05-01

Full Text Available A contínua seleção genética para maior produção de leite em conjunto com o aumento da capacidade digestiva e profundidade corporal aumentou a susceptibilidade à ocorrência de abomasopatias, incluindo o deslocamento do abomaso. Este trabalho objetivou realizar um estudo retrospectivo sobre o deslocamento de abomaso em 36 bovinos atendidos na Clínica de Bovinos, Campus Garanhuns da Universidade Federal Rural de Pernambuco, durante o período de janeiro de 2000 a fevereiro de 2009. Foram diagnosticados 27 casos de deslocamento do abomaso à direita, seis casos de deslocamento do abomaso à esquerda e três casos de vólvulo abomasal. Onze casos considerados moderados, sem grave distensão abdominal, apetite presente para a forragem e delimitação de som metálico até o 8º espaço intercostal, foram tratados clinicamente; enquanto 20 casos com distensão abdominal moderada a severa, associada a distúrbios sistêmicos, foram considerados graves e tratados cirurgicamente. Duas vacas foram eutanasiadas devido peritonite difusa ou alterações graves na serosa do abomaso, totalizando 18 animais submetidos ao tratamento cirúrgico. Dois animais foram encaminhados para abate e três vacas chegaram prostradas e morreram sem receber nenhum tratamento. A análise dos fatores de risco identificou a estação chuvosa como estatisticamente significativa. O maior número de deslocamento do abomaso ocorreu em vacas mestiças com 24 casos (66,6%, seguida por bovinos da raça Holandesa com 11 (30,5% e Gir com um (2,9% caso. A composição da alimentação oferecida variou bastante e caracterizou-se por conter excesso de carboidratos e, na maioria dos casos, fibra de baixa qualidade. Os sinais clínicos mais frequentes foram comportamento apático, desidratação, timpanismo ruminal leve a severo com motilidade ausente ou diminuída, som de líquido ao balotamento do flanco direito, som de chapinhar metálico e/ou observação de uma estrutura similar a

Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores.

Science.gov (United States)

De Koster, J; Hostens, M; Van Eetvelde, M; Hermans, K; Moerman, S; Bogaert, H; Depreester, E; Van den Broeck, W; Opsomer, G

2015-07-01

The objective of the present research was to determine the insulin response of the glucose and fatty acid metabolism in dry dairy cows with a variable body condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity 2 to 5) were selected based on BCS at the beginning of the study (2mo before expected parturition date). During the study, animals were monitored weekly for BCS and backfat thickness and in the last 2wk, blood samples were taken for determination of serum nonesterified fatty acid (NEFA) concentration. Animals underwent a hyperinsulinemic euglycemic clamp test in the third week before the expected parturition date. The hyperinsulinemic euglycemic clamp test consisted of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2, and 5mIU/kg per minute. For each insulin infusion period, a steady state was defined as a period of 30min where no or minor changes of the glucose infusion were necessary to keep the blood glucose concentration constant and near basal levels. During the steady state, the glucose infusion rate [steady state glucose infusion rate (SSGIR) in µmol/kg per minute] and NEFA concentration [steady state NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin response of the glucose and fatty acid metabolism. Dose response curves were created based on the insulin concentrations during the steady state and the SSGIR or SSNEFA. The shape of the dose response curves is determined by the concentration of insulin needed to elicit the half maximal effect (EC50) and the maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism, respectively. The maximal SSGIR was negatively associated with variables reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration during the dry period, and absolute weight of the different adipose depots determined after euthanasia and dissection of the different depots), whereas the EC50 of the glucose metabolism was

A mathematical model of brain glucose homeostasis

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Kimura Hidenori

2009-11-01

Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

DEFF Research Database (Denmark)

van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

2016-01-01

, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...... in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were...

Insulin appearance of subcutaneously infused insulin: influence of the basal rate pulse interval of the infusion pump.

Science.gov (United States)

Birch, K; Hildebrandt, P; Jensen, B M; Kühl, C; Brange, J

1985-05-01

To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.

The effects of short term intravenous infusion of a soybean based lipid emulsion on some blood constituents in sheep: A preliminary study

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Hamid Akbari

2014-04-01

Full Text Available To evaluate the effect of intravenous infusion of a soybean based lipid emulsion (Lipovenoes 10% on some blood constituents in sheep, a replicated 2 × 2 Latin square design experiment was conducted in four clinically healthy ewes. Lipid emulsion (LE group or normal saline (NS group was infused intravenously at a rate of 0.025 mL kg-1 per min for 6 hr and the concentrations of blood triglyceride, glucose, insulin, calcium, magnesium, phosphorous, sodium and potassium were measured before (baseline and then at timepoints 2, 4, 6, 12 and 24 hr after infusion. Compared to the baseline values and/or NS infusion, LE infusion resulted in a significant increase in the concentrations of triglyceride (p 0.05. In conclusion, intravenous infusion of Lipovenoes temporarily influenced some blood constituents. Increased triglyceride concentrations were associated with an increase in HOMA-IR values indicating a state of insulin resistance. No remarkable adverse effect was observed following LE infusion and lipid based emulsions can be safely used in ruminants not suffering from extensive lipid mobilization.

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Science.gov (United States)

Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo; Lee, Andrew; Tift, Michael S; Tavoni, Stephen K; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

A review of the security of insulin pump infusion systems.

Science.gov (United States)

Paul, Nathanael; Kohno, Tadayoshi; Klonoff, David C

2011-11-01

Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues. © 2011 Diabetes Technology Society.

Local and systemic response to intramammary lipopolysaccharide challenge during long-term manipulated plasma glucose and insulin concentrations in dairy cows.

Science.gov (United States)

Vernay, M C M B; Wellnitz, O; Kreipe, L; van Dorland, H A; Bruckmaier, R M

2012-05-01

The metabolic load during periods of high milk production in dairy cows causes a variety of changes of metabolite blood concentrations including dramatically decreased glucose levels. These changes supposedly impair the immune system. The goal of this study was, therefore, to evaluate adaptations of the cow's immune system in response to an intramammary lipopolysaccharide (LPS) stimulation during a 3-d modification of plasma glucose and insulin induced by different clamp infusions. Seventeen midlactating dairy cows received a hypoglycemic hyperinsulinemic clamp induced by insulin infusion (HypoG; n=5), a euglycemic hyperinsulinemic clamp induced by insulin and glucose infusion (EuG; n=6), or infusion of saline solution (NaCl; n=6) for 56 h. At 48 h of infusion, 2 udder quarters were challenged with 200 μg of Escherichia coli LPS. At 48 h of infusion (immediately before LPS challenge), tumor necrosis factor α, lactoferrin, and serum amyloid A (SAA) mRNA abundance was increased in HypoG and Il-1β mRNA abundance was decreased in EuG. After LPS challenge, plasma glucose concentration did not decrease, although plasma insulin increased simultaneously in all groups either due to enhanced endogenous release (NaCl) or due to increased insulin infusion rate (HypoG; EuG). Plasma cortisol, rectal temperatures, and milk somatic cell count of challenged quarters increased, whereas plasma nonesterified fatty acid concentrations were similarly decreased across treatments. In mammary biopsies, increased mRNA expression of tumor necrosis factor α, IL-1β, IL-8, and IL-10, and SAA were observed in LPS-treated quarters of all groups, with a more pronounced increase in IL-1β, IL-10, and SAA expression in EuG. Nuclear factor-κB mRNA expression was upregulated in NaCl and EuG but not in HypoG in response to LPS. Lactoferrin, toll-like receptor 4, and cyclooxygenase-2 mRNA expression was increased in LPS-treated quarters of EuG only, and 5-lipoxygenase mRNA expression was decreased

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes

International Nuclear Information System (INIS)

Shaw, J.H.; Wolfe, R.R.

1988-01-01

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC

Glucose kinetics at rest and during exercise in gluconeogenesis-inhibited rats

International Nuclear Information System (INIS)

Turcotte, L.P.

1988-01-01

To evaluate the role played by gluconeogenesis in blood glucose homeostasis, untrained and trained rats were injected with mercaptopicolinic acid (MPA), a known inhibitor of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase. Glucose turnover, recycling and oxidation rates were assessed by primed-continuous infusion of [U- 14 C]- and [6- 3 H] glucose at rest and during submaximal exercise at 13.4 m/min on level grade. When compared to the untrained sham-injected animals, the untrained MPA-treated animals had 22% lower and 44% higher resting blood glucose and lactate concentrations, respectively. Resting glucose turnover, calculated from [6- 3 H]glucose, was 32% lower in the MPA-treated animals than in the sham-injected animals. During exercise, turnover increased in the sham-injected animals but remained unchanged in the MPA-treated animals. MPA-treated animals had no glucose recycling at rest or during exercise. Exercise further decreased blood glucose concentration and increased blood lactate concentration in the MPA-treated animals, but MPA treatment did not change the exercise-induced increases in glucose oxidation rate, % total VCO 2 arising from glucose oxidation and metabolic clearance rate of glucose

Nitrogen retention response to the abomasal infusion of amino acids

African Journals Online (AJOL)

HESTER LINDE

Hatfield, 1968; Nimrick et al., 1970), in diets containing high levels of urea ... body protein synthesis, determined by the ideal protein concept, are histidine, .... The first two days were an adaptation period, and sampling of urine and faeces.

Alterations in glucose kinetics induced by pentobarbital anesthesia

International Nuclear Information System (INIS)

Lang, C.H.; Bagby, G.J.; Spitzer, J.J.

1986-01-01

Pentobarbital is a common anesthetic agent used in animal research that is known to alter sympathetic function and may also affect carbohydrate metabolism. The in vivo effects of iv pentobarbital on glucose homeostasis were studied in chronically catheterized fasted rats. Whole body glucose kinetics, assessed by the constant iv infusion of [6- 3 H]- and [U- 14 C]-glucose, were determined in all rats in the conscious state. Thereafter, glucose metabolism was followed over the next 4 hr in 3 subgroups of rats; conscious, anesthetized with body temperature maintained, and anesthetized with body temperature not maintained. Hypothermia (a 5 0 C decrease) developed spontaneously in anesthetized rats kept at ambient temperature (22 0 C). No differences were seen in MABP and heart rate between conscious and normothermic anesthetized rats; however, hypothermic anesthetized rats showed a decrease in MABP (20%) and heart rate (35%). Likewise, plasma glucose and lactate concentrations, the rate of glucose appearance (Ra), recycling and metabolic clearance (MCR) did not differ between conscious and normothermic anesthetized animals. In contrast, hypothermic anesthetized rats showed a 50% reduction in plasma lactate, a 40% drop in glucose Ra, and a 30-40% decrease in glucose recycling and MCR. Thus, pentobarbital does not appear to alter in vivo glucose kinetics, compared to unanesthetized controls, provided that body temperature is maintained

Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Christensen, Mikkel; Calanna, Salvatore; Sparre-Ulrich, Alexander H

2015-01-01

constituted a "recovery phase." During the recovery phase, GIP infusions elicited larger glucagon responses (164 ± 50 [GIP] vs. 23 ± 25 [GLP-1] vs. 17 ± 46 [saline] min ⋅ pmol/L, P endogenous glucose production was higher with GIP and lower with GLP-1 compared with saline (P ... days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 [GIP] vs. 232 ± 40 [GLP-1] vs. 212 ± 56 [saline] mg ⋅ kg(-1), P ... similar on all days. Our results suggest that during hypoglycemia in patients with T1DM, exogenous GIP increases glucagon responses during the recovery phase after hypoglycemia and reduces the need for glucose administration....

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

DEFF Research Database (Denmark)

Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

2002-01-01

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...... = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole...

Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis

DEFF Research Database (Denmark)

Gyldenløve, M; Lauritsen, Tina Vilsbøll; Zachariae, Claus

2015-01-01

BACKGROUND: Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed...... the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE: To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon...... and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS: Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS: In patients...

Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

Science.gov (United States)

Al-Niaimi, Ahmed N; Ahmed, Mostafa; Burish, Nikki; Chackmakchy, Saygin A; Seo, Songwon; Rose, Stephen; Hartenbach, Ellen; Kushner, David M; Safdar, Nasia; Rice, Laurel; Connor, Joseph

2015-01-01

SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics. Copyright © 2014. Published by Elsevier Inc.

Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans

DEFF Research Database (Denmark)

Simon, Marie-Christine; Strassburger, Klaus; Nowotny, Bettina

2015-01-01

production. Muscle and hepatic lipid contents were assessed by (1)H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays. RESULTS: In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2....... reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose...... cytokines. CONCLUSIONS: Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic...

Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

DEFF Research Database (Denmark)

Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

2003-01-01

(HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during...... not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes....

Glucose turnover in 48-hour-fasted running rats

International Nuclear Information System (INIS)

Sonne, B.; Mikines, K.J.; Galbo, H.

1987-01-01

In fed rats, hyperglycemia develops during exercise. This contrasts with the view based on studies of fasted human and dog that euglycemia is maintained in exercise and glucose production (R/sub a/) controlled by feedback mechanisms. Forty-eight-hour-fasted rats (F) were compared to fed rats (C) and overnight food-restricted (FR) rats. [3- 3 H]- and [U- 14 C]glucose were infused and blood and tissue sampled. During running (21 m/min, 0% grade) R/sub a/ increased most in C and least in F and only in F did R/sub a/ not significantly exceed glucose disappearance. Plasma glucose increased more in C (3.3 mmol/1) than in FR (1.6 mmol/l) and only modestly (0.6 mmol/l) and transiently in F. Resting liver glycogen and exercise glycogenolysis were highest in C and similar in FR and F. Resting muscle glycogen and exercise glycogenolysis were highest in C and lowest in F. During running, lactate production and gluconeogenesis were higher in FR than in F. At least in rats, responses of production and plasma concentration of glucose to exercise depend on size of liver and muscle glycogen stores; glucose production matches increase in clearance better in fasted than in fed states. Probably glucose production is stimulated by feedforward mechanisms and feedback mechanisms are added if plasma glucose decreases

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Directory of Open Access Journals (Sweden)

Anders Lyngvi Fougner

2016-04-01

Full Text Available Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP sensor sites, as an alternative to the SC location. Intraarterial (IA and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L. Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s, and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min. IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects

DEFF Research Database (Denmark)

Kjems, Lise L; Holst, Jens J; Vølund, Aage

2003-01-01

. However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2...

Continuous tissue glucose monitoring correlates with measurement of intermittent capillary glucose in patients with distributive shock.

Science.gov (United States)

Ballesteros, D; Martínez, Ó; Blancas Gómez-Casero, R; Martín Parra, C; López Matamala, B; Estébanez, B; Chana, M

2015-10-01

Intermittent glycemic measurements in patients admitted to the intensive care unit (ICU) can result in episodes of severe hypoglycemia or in a poor control of glycemia range. We designed a study to assess accuracy and reliability of continuous monitoring of tissue glucose for patients with distributive shock. Consecutive patients admitted to the ICU with a diagnosis of distributive shock and the need of insulin infusion for glycemic control were included in the study. These patients were implanted a Continuous Glucose Control Monitoring System (CGMS) with the sensor inserted subcutaneously into the abdominal wall. CGMS values were recorded every 5min. Capillary glucose (CG) was monitored for adjusting insulin perfusion according to the ICU protocol. Correlation between both methods was assessed. A total of 11,673 CGMS and 348 CG values were recorded. In five patients, CGMS failed to detect tissue glucose. A glucose value <3.33mmol/l (<60mg/dl) was observed in 3.6% of CGMS and in 0.29% CG values. 295 pairs of measurements were included in the statistical analysis for correlation assessment. The intraclass correlation coefficient was 0.706. The Pearson correlation coefficient was 0.71 (p<0.0001, 95% CI 0.65-0.76). The mean of differences between both measurement methods was 0.22mmol/l (3.98mg/dl) (95% CI 0.66-7.31). When the Continuous Glucose Control Monitoring System (CGMS) is able to obtain data (75% of the patients), there is correlation between the values obtained by this method and capillary blood glucose in patients with distributive shock. CGMS can detect more episodes of glycemic excursions outside the normal range than intermittent capillary glucose monitoring. Variables that may impair glucose metabolism and peripheral soft tissues perfusion could impair CGMS measurements. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Field trial on glucose-induced insulin and metabolite responses in Estonian Holstein and Estonian Red dairy cows in two herds

Directory of Open Access Journals (Sweden)

Kaart Tanel

2010-01-01

Full Text Available Abstract Background Insulin secretion and tissue sensitivity to insulin is considered to be one of the factors controlling lipid metabolism post partum. The objective of this study was to compare glucose-induced blood insulin and metabolite responses in Estonian Holstein (EH, n = 14 and Estonian Red (ER, n = 14 cows. Methods The study was carried out using the glucose tolerance test (GTT performed at 31 ± 1.9 days post partum during negative energy balance. Blood samples were obtained at -15, -5, 5, 10, 20, 30, 40, 50 and 60 min relative to infusion of 0.15 g/kg BW glucose and analysed for glucose, insulin, triglycerides (TG, non-esterified fatty acids (NEFA, cholesterol and β-hydroxybutyrate (BHB. Applying the MIXED Procedure with the SAS System the basal concentration of cholesterol, and basal concentration and concentrations at post-infusion time points for other metabolites, area under the curve (AUC for glucose and insulin, clearance rate (CR for glucose, and maximum increase from basal concentration for glucose and insulin were compared between breeds. Results There was a breed effect on blood NEFA (P P P P P P th min nadir (P th min postinfusion (P Conclusion Our results imply that glucose-induced changes in insulin concentration and metabolite responses to insulin differ between EH and ER dairy cows.

Increased glucose dependence in resting, iron-deficient rats

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Brooks, G.A.; Henderson, S.A.; Dallman, P.R.

1987-01-01

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 ± 0.2 compared with 13.8 ± 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6- 3 H]glucose and sodium L-[U- 14 C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly higher blood glucose and lactate concentrations than controls. The iron-deficient group had a significantly higher glucose turnover rate than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14 C into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover rates between deficient rats and controls was attributed to 14 C recycling. The results indicate a greater dependence on glucose metabolism in iron-deficient rats

The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

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Karstoft, Kristian; P. Mortensen, Stefan; H. Knudsen, Sine

2015-01-01

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under eu- and hyperglycemic conditions. Young, healthy males (n=10) underwent three trials in a randomized, controlled, cross-over study. Each trial c...... hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially, however, due to increased insulin levels....... consisted of a 2-stage (eu- and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism were measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial and common carotid artery blood flow...... or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance (Rd) during GLP-1 compared to CON and GIP (Plevels, no differences between trials were seen for GIR or glucose Rd. Besides...

Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

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Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid].

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Arranz Martín, Alfonso; Calle Pascual, Alfonso; Del Cañizo Gómez, Francisco Javier; González Albarrán, Olga; Lisbona Gil, Arturo; Botella Serrano, Marta; Pallardo Sánchez, Luis Felipe

2015-04-01

To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients

Directory of Open Access Journals (Sweden)

Jerzy Szewczyk

2017-01-01

Full Text Available Background:It is now widely accepted that bariatric surgeries such as Roux-en-Y gastric bypass (RYGB and sleeve gastrectomy (SG can resolve orimprove type 2 diabetes mellitus. Post-prandial glucagon-like peptide-1(GLP-1 increases after both RYGB and SG and blockade of the GLP-1 receptor suppresses the hypoglycemic effect post-operatively. The expedited delivery of nutrients, including L-glutamine and butyrate, to the distal small intestine and colon, where most GLP-1–secreting enteroendocrine L-cells are expressed, could explain this increase post-surgery. Pharmacological treatments that target nutrient-sensing receptors on L-cells may mimic the effects of bariatric surgeries and may ameliorate deficiencies in gut hormone responses involved in the regulation of glucose and satiety. In this study, we investigated the effects of the colonic delivery of L-glutamine and butyrate on GLP-1 secretion and glucose homeostasis in both a pre-clinical rodent model and clinical type 2 diabetes mellitus (T2DM. Results: Infusion of 4.4mg of sodium butyrate, compared to saline, into the colon of Zuckerdiabetic fatty (ZDF rats increased GLP-1secretion in response to an intra-duodenal glucose challenge. In a chronic study, oral dosing of 40mg of sodium butyrate twice a day, formulated as colon-targeted sustained-release tablets, preserved glucose tolerance and insulin sensitivity in ZDF rats. In ten T2DM patients requiring oral anti-hyperglycemic agents, infusion of 1g of L-glutamine into the colon, compared to saline, increased plasma GLP-1 (p=0.017 at 30min and insulin (p<0.01 at 90min; p=0.001 at 120min; AUC p<0.005 after an oral glucose challenge. infusion with butyrate significantly increased only insulin secretion at 120min, compared to saline (p<0.05. Neither agent had an effect on glucose disposal.Conclusion: Targeted colonic delivery of L-glutamine and butyrate augments secretion of meal-stimulated GLP-1 and insulin; L-glutamine was more efficacious in

A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects

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Vahidi, O; Kwok, K E; Gopaluni, R B

2016-01-01

We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main...... variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data...... obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization...

Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

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Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

2015-01-01

Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether......-mediated glucose uptake in skeletal muscle by 90% (Prights...

Localization and mobility of glucose-coated gold nanoparticles within the brain.

Science.gov (United States)

Gromnicova, Radka; Yilmaz, Canan Ugur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather; Williams, Phil; Romero, Ignacio A; Sharrack, Basil; Male, David

2016-03-01

To identify the localization of glucose-coated gold nanoparticles within cells of the brain after intravascular infusion which may point to the mechanism by which they cross the blood-brain barrier. Tissue distribution of the nanoparticles was measured by inductively-coupled-mass spectrometry and localization within the brain by histochemistry and electron microscopy. Nanoparticles were identified within neurons and glial cells more than 10 μm from the nearest microvessel within 10 min of intracarotid infusion. Their distribution indicated movement across the endothelial cytosol, and direct transfer between cells of the brain. The rapid movement of this class of nanoparticle (brain demonstrates their potential to carry therapeutic biomolecules or imaging reagents.

Glucose homeostasis in rainbow trout fed a high-carbohydrate diet: metformin and insulin interact in a tissue-dependent manner.

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Polakof, S; Moon, T W; Aguirre, P; Skiba-Cassy, S; Panserat, S

2011-01-01

Carnivorous fish species such as the rainbow trout (Oncorhynchus mykiss) are considered to be "glucose intolerant" because of the prolonged hyperglycemia experienced after intake of a carbohydrate-enriched meal. In the present study, we use this species to study glucose homeostasis in fish chronically infused with the hypoglycemic agents, insulin, and metformin, and fed with a high proportion of carbohydrates (30%). We analyzed liver, skeletal muscle, and white adipose tissue (WAT), which are insulin- and metformin-specific targets at both the biochemical and molecular levels. Trout infused with the combination of insulin and metformin can effectively utilize dietary glucose at the liver, resulting in lowered glycemia, increased insulin sensitivity, and glucose storage capacity, combined with reduced glucose output. However, in both WAT and skeletal muscle, we observed decreased insulin sensitivity with the combined insulin + metformin treatment, resulting in the absence of changes at the metabolic level in the skeletal muscle and an increased potential for glucose uptake and storage in the WAT. Thus, the poor utilization by rainbow trout of a diet with a high proportion of carbohydrate can at least be partially improved by a combined treatment with insulin and metformin, and the glucose intolerance observed in this species could be, in part, due to some of the downstream components of the insulin and metformin signaling pathways. However, the predominant effects of metformin treatment on the action of insulin in these three tissues thought to be involved in glucose homeostasis remain exclusive in this species.

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

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Bollmann, Marc-Daniel; Revelly, Jean-Pierre; Tappy, Luc; Berger, Mette M; Schaller, Marie-Denise; Cayeux, Marie-Christine; Martinez, Alexandre; Chioléro, René-Louis

2004-06-01

To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. Each patient received the two buffers in a randomized sequence over two consecutive days. The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Direct effects of exendin-(9,39) and GLP-1-(9,36)amide on insulin action, β-cell function, and glucose metabolism in nondiabetic subjects.

Science.gov (United States)

Sathananthan, Matheni; Farrugia, Luca P; Miles, John M; Piccinini, Francesca; Dalla Man, Chiara; Zinsmeister, Alan R; Cobelli, Claudio; Rizza, Robert A; Vella, Adrian

2013-08-01

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10(-4) dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10(-14) dL/kg/min(2) per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Whole body glucose kinetics in type I diabetes studied with [6,6-2H] and [U-13C]-glucose and the artificial B-cell

International Nuclear Information System (INIS)

Darmaun, D.; Cirillo, D.; Koziet, J.; Chauvet, D.; Young, V.R.; Robert, J.J.

1988-01-01

Dynamic aspects of whole body glucose metabolism were assessed in ten young adult insulin-dependent (type I) diabetic men. Using a primed, continuous intravenous infusion of [6,6- 2 H]glucose and [U- 13 C]glucose, endogenous production, tissue uptake, carbon recycling, and oxidation of glucose were measured in the postabsorptive state. These studies were undertaken after blood glucose had been maintained overnight at 5.9 +/- 0.4 mmol/L (n = 10), and on another night at 10.5 +/- 0.4 mmol/L (n = 4) or 15.2 +/- 0.6 mmol/L (n = 6). In the normoglycemic state, endogenous glucose production averaged 2.15 +/- 0.13 mg x kg-1 x min-1. This value, as well as the rate of glucose carbon recycling (0.16 +/- 0.04 mg x kg-1 x min-1) and glucose oxidation (1.52 +/- 0.16 mg x kg-1 x min-1) are comparable to those found in nondiabetic controls. In the hyperglycemic states at 10 or 15 mmol/L, endogenous glucose production was increased by 11% (P less than .01) and 60% (P less than .01) compared to the normoglycemic states, respectively. Glucose carbon recycling contributed only a small percentage to this variation in glucose production (15% at the 15 mmol/L glucose level). This suggests that if gluconeogenesis participates in the increased glucose output, it is not dependent on a greater systemic supply of three-carbon precursors. The increased rate of glucose production in the hyperglycemic state was quantitatively offset by a rise in urinary glucose excretion. Glucose tissue uptake, as well as glucose oxidation, did not vary between normoglycemic and hyperglycemic states

Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

DEFF Research Database (Denmark)

Asmar, Meena; Højberg, Patricia V; Deacon, Carolyn F

2010-01-01

glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (PAUC amylin/C-peptide ratio was similar on both......This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood...... amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks...

Pancreatic ß-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

DEFF Research Database (Denmark)

Asmar, Meena; Højberg, Patricia; Deacon, Carolyn F.

2010-01-01

glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (PAUC amylin/C-peptide ratio was similar on both......This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood...... amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks...

Effect of Intravenous Small-Volume Hypertonic Sodium Bicarbonate, Sodium Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in Hyperkalemic Neonatal Calves with Diarrhea.

Science.gov (United States)

Trefz, F M; Constable, P D; Lorenz, I

2017-05-01

Hyperkalemia is a frequently observed electrolyte imbalance in dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness and life-threatening cardiac conduction abnormalities and arrhythmias. Intravenous administration of a small-volume hypertonic NaHCO 3 solution is clinically more effective in decreasing the plasma potassium concentration (cK) in hyperkalemic diarrheic calves than hypertonic NaCl or glucose solutions. Twenty-two neonatal diarrheic calves with cK >5.8 mmol/L. Prospective randomized clinical trial. Calves randomly received either 8.4% NaHCO 3 (6.4 mL/kg BW; n = 7), 7.5% NaCl (5 mL/kg BW; n = 8), or 46.2% glucose (5 mL/kg BW; n = 7) IV over 5 minutes and were subsequently allowed to suckle 2 L of an electrolyte solution. Infusions with NaHCO 3 and NaCl provided an identical sodium load of 6.4 mmol/kg BW. Hypertonic NaHCO 3 infusions produced an immediate and sustained decrease in plasma cK. Hypertonic glucose infusions resulted in marked hyperglycemia and hyperinsulinemia, but cK remained unchanged for 20 minutes. Between 30 and 120 minutes after initiation of treatment, the most marked decrements in cK from baseline occurred in group NaHCO 3 , which were significantly (P < .05) larger during this period of time than in calves in group NaCl, but not group glucose. After 120 minutes, the mean decrease in cK from baseline was -26 ± 10%, -9 ± 8%, and -22 ± 6% in groups NaHCO 3 , NaCl, and glucose, respectively. Small-volume hypertonic NaHCO 3 infusions appear to have clinical advantages for the rapid resuscitation of hyperkalemic diarrheic calves, compared to hypertonic NaCl or glucose solutions. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

DEFF Research Database (Denmark)

Hvidberg, A; Rasmussen, M H; Christensen, N J

1994-01-01

followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC......). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma......The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery...

Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus

DEFF Research Database (Denmark)

Hvidberg, A; Rosenfalck, A; Christensen, N J

1998-01-01

.0241) but there were no concomitant significant increases in plasma c-AMP or in endogenous glucose production rate. Whether the increase in glucose recovery is large enough to suggest that chronic theophylline administration will protect against insulin-induced hypoglycaemia remains unsettled....... hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m(-2...

Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

DEFF Research Database (Denmark)

Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

2003-01-01

BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

Intracerebroventricular administration of okadaic acid induces hippocampal glucose uptake dysfunction and tau phosphorylation.

Science.gov (United States)

Broetto, Núbia; Hansen, Fernanda; Brolese, Giovana; Batassini, Cristiane; Lirio, Franciane; Galland, Fabiana; Dos Santos, João Paulo Almeida; Dutra, Márcio Ferreira; Gonçalves, Carlos-Alberto

2016-06-01

Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer's disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro, particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuous-infusion adriamycin

International Nuclear Information System (INIS)

Benjamin, R.S.; Chawla, S.P.; Ewer, M.S.; Hortobagyi, G.N.

1986-01-01

This chapter discusses the diminished cardiotoxicity as well as diminished nausea and vomiting with continuous infusions of adriamycin to patients undergoing radiation therapy, particularly with infusions of 48 hours or longer, and best with 96-hour infusions, the longest duration that has been studied systematically. In breast cancer, data show that more adriamycin is better, but only for a selected subgroup of patients: those with complete remission. The diminished cardiotoxicity makes the use of adriamycin more attractive in the adjuvant situation, where increased safety will decrease the chances of long-term complications and make retreatment easy for cured patients who develop second malignancies

Glucose-lowering effect of BTS 67 582.

Science.gov (United States)

Page, T; Bailey, C J

1997-12-01

1. The hypoglycaemic effect of BTS 67 582 (1,1-dimethyl-2(2-morpholinophenyl) guanidine fumarate) was studied in normal rats. 2. BTS 67 582 (100 mg kg(-1), p.o.) acutely lowered basal plasma glucose concentrations: onset within 1 h, maximum decrease of >40% at 2-3 h, and partial return to euglycaemia by 5 h. Plasma insulin concentrations were increased: onset within 30 min, maximum increase 3 fold at 1-2 h; returning to normal by 5 h. 3. BTS 67 582 (100 mg kg(-1)) increased (by 56%) the rate of disappearance of plasma glucose during an intravenous glucose tolerance test, accompanied by a 51% increase in insulin concentrations. 4. During hyperglycaemic clamp studies BTS 67 582 (100 mg kg(-1)) increased glucose utilization 3 fold. This was associated with a 3 fold increase in insulin concentrations, even in the presence of adrenaline at a dosage which inhibits glucose-induced insulin release. 5. When the insulin-releasing effect of BTS 67 582 (100 mg kg(-1)) was inhibited by infusion of somatostatin, there was no effect on glycaemia. 6. Insulin-dependent diabetic BB/S rats, which do not produce endogenous insulin, showed no effect of BTS 67 582 (100 mg kg(-1)) on plasma glucose concentrations in the presence or absence of exogenous insulin. 7. The results demonstrate an acute hypoglycaemic effect of BTS 67 582 which appears to result mainly from its potent insulin-releasing action.

Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

International Nuclear Information System (INIS)

Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

1996-01-01

To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

Overnight Control of Blood Glucose in People with Type 1 Diabetes

DEFF Research Database (Denmark)

Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

2012-01-01

In this paper, we develop and test a Model Predictive Controller (MPC) for overnight stabilization of blood glucose in people with type 1 diabetes. The controller uses glucose measurements from a continuous glucose monitor (CGM) and its decisions are implemented by a continuous subcutaneous insulin...... infusion (CSII) pump. Based on a priori patient information, we propose a systematic method for computation of the model parameters in the MPC. Safety layers improve the controller robustness and reduce the risk of hypoglycemia. The controller is evaluated in silico on a cohort of 100 randomly generated...... patients with a representative intersubject variability. This cohort is simulated overnight with realistic variations in the insulin sensitivities and needs. Finally, we provide results for the first tests of this controller in a real clinic....

The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

DEFF Research Database (Denmark)

Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N

2013-01-01

β-cell function is improved in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to an exaggerated glucagon-like peptide 1 (GLP-1) secretion, but causality has not been established. The aim of this study...... consisted of two experimental days, allowing a meal test with infusion of saline or Ex-9 in random order. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased and glucagon secretion was augmented. GLP-1R blockade did not affect β......-cell function and meal-induced glucagon release before the operation, but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance...

Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

International Nuclear Information System (INIS)

Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

1986-01-01

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

Acute effects of ethanol and acetate on glucose kinetics in normal subjects

International Nuclear Information System (INIS)

Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.; Taskinen, M.R.

1988-01-01

The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R a was matched by a comparable decrease in glucose utilization (R d ), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R a is counterbalanced by equal inhibition of R d ; (2) basal R a and R d are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

Science.gov (United States)

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Improved lipid profile and increased serum antioxidant capacity in healthy volunteers after Sambucus ebulus L. fruit infusion consumption.

Science.gov (United States)

Ivanova, Diana; Tasinov, Oskan; Kiselova-Kaneva, Yoana

2014-09-01

This study aimed to establish the effect of Sambucus ebulus L. (SE) ripe fruit infusion on body weight, blood pressure, glucose levels, lipid profile and antioxidant markers in healthy volunteers in respect of its possible protective activity against cardiovascular diseases and other oxidative stress-related diseases. The study involved 21 healthy volunteers, aged between 20 and 59, BMI 23.12 ± 1.31, who consumed 200 ml SE infusion/day for a period of 30 d. Blood samples were collected before and at the end of the intervention. Significant decrease in triglycerides (14.92%), total cholesterol (15.04%) and LDL-C (24.67%) was established at the end of the study. In addition, HDL-C/LDL-C ratio increased by 42.77%. Improved serum antioxidant capacity and total thiol levels were also established. The results presented in this first human intervention study with SE fruit infusion indicate the potential of the plant to improve lipid profile and serum antioxidant capacity in humans.

Altered glucose kinetics in diabetic rats during Gram-negative infection

International Nuclear Information System (INIS)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

1987-01-01

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients

DEFF Research Database (Denmark)

Thondam, Sravan K; Daousi, Christina; Wilding, John P H

2017-01-01

is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n...... = 6), normoglycemic obese (n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg(-1)·min(-1)) or normal saline. Insulin, NEFA, SAT......-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0-4 h ± SE, 41,992 ± 9,843 µmol·l(-1)·min(-1) vs. 71,468 ± 13...

Infusion MR arteriography during hepatic arterial infusion chemotherapy. Evaluation of clinical usefulness

International Nuclear Information System (INIS)

Uchino, Minako; Takizawa, Kenji

2003-01-01

We developed a new method of infusion MR arteriography (IMRA) via an implantable port system using an infusion pump for the evaluation of drug distribution during hepatic arterial infusion chemotherapy. The purposes of this study were to optimize the method and evaluate its clinical usefulness. We used 3D-T1 turbo field echo (TFE) as the most suitable sequence for IMRA according to the results of a phantom model experiment. We examined 33 cases of liver cancer that had been treated by arterial infusion chemotherapy via the port system. The following investigations were performed: degree of tumor enhancement, intra- and extra- hepatic perfusion abnormality, and related toxicity. The evaluation of images was performed separately by two radiologists. IMRA provided good images of contrast enhancement, to reveal the perfusion patterns. The treatment response rate in the tumor group with well enhancement was higher than that of the group with poor enhancement (p<0.0001). Extrahepatic perfusion was well visualized and was correlated with toxicity (p<0.0001). IMRA is a useful method to evaluate drug perfusion for the optimization of arterial infusion chemotherapy. (author)

Diversity of gastrointestinal helminths in Dall's sheep and the negative association of the abomasal nematode, Marshallagia marshalli, with fitness indicators.

Science.gov (United States)

Aleuy, O Alejadro; Ruckstuhl, Kathreen; Hoberg, Eric P; Veitch, Alasdair; Simmons, Norman; Kutz, Susan J

2018-01-01

Gastrointestinal helminths can have a detrimental effect on the fitness of wild ungulates. Arctic and Subarctic ecosystems are ideal for the study of host-parasite interactions due to the comparatively simple ecological interactions and limited confounding factors. We used a unique dataset assembled in the early seventies to study the diversity of gastrointestinal helminths and their effect on fitness indicators of Dall's sheep, Ovis dalli dalli, in the Mackenzie Mountains, Northwest Territories, Canada. Parasite diversity included nine species, among which the abomasal nematode Marshallagia marshalli occurred with the highest prevalence and infection intensity. The intensity of M. marshalli increased with age and was negatively associated with body condition and pregnancy status in Dall's sheep across all the analyses performed. The intensity of the intestinal whipworm, Trichuris schumakovitschi, decreased with age. No other parasites were significantly associated with age, body condition, or pregnancy. Our study suggests that M. marshalli might negatively influence fitness of adult female Dall's sheep.

An audit of hospital based outpatient infusions and a pilot program of community-based monoclonal antibody infusions.

LENUS (Irish Health Repository)

Doran, J-P

2012-02-01

INTRODUCTION: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor alpha, is administered as an intravenous infusion requiring a costly hospital day case or inpatient admission. METHODS: An audit of all current therapies given by intravenous infusions in an outpatient setting in St Vincent\\'s University Hospital (SVUH) was undertaken. Furthermore, in conjunction with TCP homecare, we established in a general practise health clinic, the first Irish community infusion centre for the administration of infliximab in August 2006. RESULTS: All outpatient departments indicated that they would favour a centralized hospital infusion unit. There were no adverse events and the mean global satisfaction improved in the community infliximab infusion pilot programme of seven patients. CONCLUSION: This study suggests efficiencies in providing centralized infusion facilities, while the community based infusion of infliximab is feasible and safe in this small cohort and identifies the community infusion unit as a viable and cost efficient alternative for administration of infliximab.

The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

DEFF Research Database (Denmark)

Pilgaard, K; Jensen, C; Schou, J

2009-01-01

h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic...... and peripheral insulin action. RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p ...-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p

In vitro viability effects on apheresis and buffy-coat derived platelets administered through infusion pumps

Directory of Open Access Journals (Sweden)

Sandgren P

2014-12-01

Full Text Available Per Sandgren,1,2 Veronica Berggren,3 Carl Westling,1,2 Viveka Stiller1 1Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 2Department of Laboratory Medicine, Karolinska Institutet, 3Department of Neonatology, Karolinska University Hospital, Stockholm, SwedenBackground: Different infusion pump systems as well as gravity infusion have been widely used in neonatal transfusion. However, the limited number of published studies describing the use of infusion pumps on platelets illustrates the necessity for more robust data.Methods: To evaluate the potential in vitro effects on the cellular, metabolic, functional and phenotypic properties of platelets, we set up a four-arm paired study simultaneously comparing the use of different infusion pumps (Alaris® CC/GP with unexposed platelets. The platelet units (n=8 were either produced by the apheresis technique and suspended in 100% plasma or derived from buffy coats to yield platelet units stored in approximately 30% plasma and 70% SSP+. Fresh and 5-day old platelets were tested.Results: Regardless of the production system or storage time used, no significant differences were observed in glucose and lactate concentration, pH, adenosine triphosphate levels, response to extent of shape change, hypotonic shock response reactivity, and CD62P expression. Similarly, no differences were observed in expression of the conformational epitope on glycoprotein IIb/IIIa, determined using procaspase-activating compound 1, or in the expression of CD42b and platelet-endothelial cell adhesion molecule-1 in a comparison between platelets administered through infusion pumps versus unexposed platelets.Conclusion: Using Alaris CC/GP infusion pumps had no influence on the cellular, functional, and phenotypic in vitro properties of platelets. This fact seems not to be affected by different production systems or storage time.Keywords: platelets, neonatal platelet transfusion

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

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Shichun Du

2014-01-01

Full Text Available Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1 was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo.

Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

Science.gov (United States)

Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

2016-01-01

Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

Glucose metabolism in critically ill patients

DEFF Research Database (Denmark)

Nielsen, Signe Tellerup; Krogh-Madsen, Rikke; Møller, Kirsten

2015-01-01

glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar......, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood...

Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

International Nuclear Information System (INIS)

Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

2008-01-01

Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)

Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

DEFF Research Database (Denmark)

Kjær, Michael; Mikines, K J; Christensen, N J

1984-01-01

Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was 1...... +/- 6 mU X l-1), and pancreatic polypeptide (361 +/- 84 vs. 180 +/- 29 pmol X l-1) reached higher levels (P less than 0.05) and glucagon (28 +/- 3 vs. 47 +/- 10 pmol X l-1) lower levels in T than in C subjects. Blood pressures changed earlier in athletes during insulin infusion, and early recovery...

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

Energy Technology Data Exchange (ETDEWEB)

Jeevanandam, M.; Young, D.H.; Schiller, W.R. (St. Joseph' s Hospital Medical Center, Phoenix, AZ (USA))

1990-05-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both (6-3H) glucose and (U-14C) glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of (6-3H) glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with (U-14C) glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury.

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

International Nuclear Information System (INIS)

Jeevanandam, M.; Young, D.H.; Schiller, W.R.

1990-01-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both [6-3H] glucose and [U-14C] glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of [6-3H] glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with [U-14C] glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

Science.gov (United States)

Veldhuis, Johannes D; Olson, Thomas P; Takahashi, Paul Y; Miles, John M; Joyner, Michael J; Yang, Rebecca J; Wigham, Jean

2015-09-01

Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans

DEFF Research Database (Denmark)

Battram, D S; Graham, T E; Dela, F

2007-01-01

Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether...

Plasma Volume Expansion Resulting from Intravenous Glucose Tolerance Test

Directory of Open Access Journals (Sweden)

Robert G. Hahn

2011-01-01

Full Text Available Objective. To quantify the degree of plasma volume expansion that occurs during an intravenous glucose tolerance test (IVGTT. Methods. Twenty healthy volunteers (mean age, 28 years underwent IVGTTs in which 0.3 g/kg of glucose 30% was injected as a bolus over 1 min. Twelve blood samples were collected over 75 min. The plasma glucose and blood hemoglobin concentrations were used to calculate the volume distribution (Vd and the clearance (CL of both the exogenous glucose and the injected fluid volume. Results. The IVGTT caused a virtually instant plasma volume expansion of 10%. The half-life of the glucose averaged 15 min and the plasma volume expansion 16 min. Correction of the fluid kinetic model for osmotic effects after injection reduced CL for the infused volume by 85%, which illustrates the strength of osmosis in allocating fluid back to the intracellular fluid space. Simulations indicated that plasma volume expansion can be reduced to 60% by increasing the injection time from 1 to 5 min and reducing the glucose load from 0.3 to 0.2 g/kg. Conclusion. A regular IVGTT induced an acute plasma volume expansion that peaked at 10% despite the fact that only 50–80 mL of fluid were administered.

Influence of ketamine on regional brain glucose use

International Nuclear Information System (INIS)

Davis, D.W.; Mans, A.M.; Biebuyck, J.F.; Hawkins, R.A.

1988-01-01

The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with [6- 14 C]glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic, steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus

Glucose feeds the TCA cycle via circulating lactate.

Science.gov (United States)

Hui, Sheng; Ghergurovich, Jonathan M; Morscher, Raphael J; Jang, Cholsoon; Teng, Xin; Lu, Wenyun; Esparza, Lourdes A; Reya, Tannishtha; Le Zhan; Yanxiang Guo, Jessie; White, Eileen; Rabinowitz, Joshua D

2017-11-02

Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear. Here we systematically examine the fluxes of circulating metabolites in mice, and find that lactate can be a primary source of carbon for the TCA cycle and thus of energy. Intravenous infusions of 13 C-labelled nutrients reveal that, on a molar basis, the circulatory turnover flux of lactate is the highest of all metabolites and exceeds that of glucose by 1.1-fold in fed mice and 2.5-fold in fasting mice; lactate is made primarily from glucose but also from other sources. In both fed and fasted mice, 13 C-lactate extensively labels TCA cycle intermediates in all tissues. Quantitative analysis reveals that during the fasted state, the contribution of glucose to tissue TCA metabolism is primarily indirect (via circulating lactate) in all tissues except the brain. In genetically engineered lung and pancreatic cancer tumours in fasted mice, the contribution of circulating lactate to TCA cycle intermediates exceeds that of glucose, with glutamine making a larger contribution than lactate in pancreatic cancer. Thus, glycolysis and the TCA cycle are uncoupled at the level of lactate, which is a primary circulating TCA substrate in most tissues and tumours.

Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites

NARCIS (Netherlands)

Nijs, H. G.; Radder, J. K.; Poorthuis, B. J.; Krans, H. M.

1990-01-01

To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves

Pituitary adenylate cyclase-activating polypeptide stimulates glucose production via the hepatic sympathetic innervation in rats.

Science.gov (United States)

Yi, Chun-Xia; Sun, Ning; Ackermans, Mariette T; Alkemade, Anneke; Foppen, Ewout; Shi, Jing; Serlie, Mireille J; Buijs, Ruud M; Fliers, Eric; Kalsbeek, Andries

2010-07-01

The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. Intracerebroventricular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production.

Effect of steel and teflon infusion catheters on subcutaneous adipose tissue blood flow and infusion counter pressure in humans

DEFF Research Database (Denmark)

Højbjerre, Lise; Skov-Jensen, Camilla; Kaastrup, Peter

2009-01-01

BACKGROUND: Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local...... microcirculation and infusion counter pressure. METHODS: One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel...... catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood...

Mathematical model of glucose-insulin homeostasis in healthy rats.

Science.gov (United States)

Lombarte, Mercedes; Lupo, Maela; Campetelli, German; Basualdo, Marta; Rigalli, Alfredo

2013-10-01

According to the World Health Organization there are over 220 million people in the world with diabetes and 3.4 million people died in 2004 as a consequence of this pathology. Development of an artificial pancreas would allow to restore control of blood glucose by coupling an infusion pump to a continuous glucose sensor in the blood. The design of such a device requires the development and application of mathematical models which represent the gluco-regulatory system. Models developed by other research groups describe very well the gluco-regulatory system but have a large number of mathematical equations and require complex methodologies for the estimation of its parameters. In this work we propose a mathematical model to study the homeostasis of glucose and insulin in healthy rats. The proposed model consists of three differential equations and 8 parameters that describe the variation of: blood glucose concentration, blood insulin concentration and amount of glucose in the intestine. All parameters were obtained by setting functions to the values of glucose and insulin in blood obtained after oral glucose administration. In vivo and in silico validations were performed. Additionally, a qualitative analysis has been done to verify the aforementioned model. We have shown that this model has a single, biologically consistent equilibrium point. This model is a first step in the development of a mathematical model for the type I diabetic rat. Copyright © 2013 Elsevier Inc. All rights reserved.

The ratio of acetate-to-glucose oxidation in astrocytes from a single 13C NMR spectrum of cerebral cortex.

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Marin-Valencia, Isaac; Hooshyar, M Ali; Pichumani, Kumar; Sherry, A Dean; Malloy, Craig R

2015-01-01

The (13) C-labeling patterns in glutamate and glutamine from brain tissue are quite different after infusion of a mixture of (13) C-enriched glucose and acetate. Two processes contribute to this observation, oxidation of acetate by astrocytes but not neurons, and preferential incorporation of α-ketoglutarate into glutamate in neurons, and incorporation of α-ketoglutarate into glutamine in astrocytes. The acetate:glucose ratio, introduced previously for analysis of a single (13) C NMR spectrum, provides a useful index of acetate and glucose oxidation in the brain tissue. However, quantitation of relative substrate oxidation at the cell compartment level has not been reported. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes, based on the standard assumption that neurons do not oxidize acetate. Mice were infused with [1,2-(13) C]acetate and [1,6-(13) C]glucose, and proton decoupled (13) C NMR spectra of cortex extracts were acquired. A fit of those spectra to the model indicated that (13) C-labeled acetate and glucose contributed approximately equally to acetyl-CoA (0.96) in astrocytes. As this method relies on a single (13) C NMR spectrum, it can be readily applied to multiple physiologic and pathologic conditions. Differences in (13) C labeling of brain glutamate and glutamine have been attributed to metabolic compartmentation. The acetate:glucose ratio, introduced for description of a (13) C NMR (nuclear magnetic resonance) spectrum, is an index of glucose and acetate oxidation in brain tissue. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes from a single NMR spectrum. As kinetic analysis is not required, the method is readily applicable to analysis of tissue extracts. α-KG = alpha-ketoglutarate; CAC = citric acid cycle; GLN = glutamine; GLU = glutamate. © 2014 International Society for Neurochemistry.

Mapping glucose-mediated gut-to-brain signalling pathways in humans.

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Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T

2014-08-01

Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.

Mapping glucose-mediated gut-to-brain signalling pathways in humans☆

Science.gov (United States)

Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.

2014-01-01

Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436

Impaired brain energy gain upon a glucose load in obesity.

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Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

2018-03-06

There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

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Gabriel, Janice

2014-11-01

Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.

Nurse- vs nomogram-directed glucose control in a cardiovascular intensive care unit.

Science.gov (United States)

Chant, Clarence; Mustard, Mary; Thorpe, Kevin E; Friedrich, Jan O

2012-07-01

Paper-based nomograms are reasonably effective for achieving glycemic control but have low adherence and are less adaptive than nurses' judgment. To compare efficacy (glucose control) and safety (hypoglycemia) achieved by use of a paper nomogram versus nurses' judgment. Prospective, randomized, open-label, crossover trial in an intensive care unit in postoperative patients with glucose concentrations greater than 8 mmol/L. Consenting nurses with at least 1 year of experience were randomized to use either their judgment or a validated paper-based nomogram for glucose control. After completion of 2 study shifts, the nurses used the alternative method for the next 2 study shifts. Glucose target level and safety and efficacy boundaries were the same for both methods. The primary end point was area under glucose time curve per hour. Thirty-four nurses contributed 95 shifts of data (44 nomogram-directed, 51 nurse-directed). Adherence to the nomogram was higher in the nomogram group than hypothetical adherence in the nurse-directed group for correct adjustments in insulin infusion (70% vs 37%; P unit where nurses generally accepted the need for tight glucose control, nurse-directed control was as effective and as safe as nomogram-based control.

Green tea extract does not affect exogenous glucose appearance but reduces insulinemia with glucose ingestion in exercise recovery.

Science.gov (United States)

Martin, Brian J; McGlory, Chris; MacInnis, Martin J; Allison, Mary K; Phillips, Stuart M; Gibala, Martin J

2016-12-01

We reported that supplementation with green tea extract (GTE) lowered the glycemic response to an oral glucose load following exercise, but via an unknown mechanism (Martin BJ, MacInnis MJ, Gillen JB, Skelly LE, Gibala MJ. Appl Physiol Nutr Metab 41: 1057-1063, 2016. Here we examined the effect of supplementation with GTE on plasma glucose kinetics on ingestion of a glucose beverage during exercise recovery. Eleven healthy, sedentary men (21 ± 2 yr old; body mass index = 23 ± 4 kg/m 2 , peak O 2 uptake = 38 ± 7 ml·kg -1 ·min -1 ; means ± SD) ingested GTE (350 mg) or placebo (PLA) thrice daily for 7 days in a double-blind, crossover design. In the fasted state, a primed constant infusion of [U- 13 C 6 ]glucose was started, and 1 h later, subjects performed a graded exercise test (25 W/3 min) on a cycle ergometer. Immediately postexercise, subjects ingested a 75-g glucose beverage containing 2 g of [6,6- 2 H 2 ]glucose, and blood samples were collected every 10 min for 3 h of recovery. The rate of carbohydrate oxidation was lower during exercise after GTE vs. PLA (1.26 ± 0.34 vs. 1.48 ± 0.51 g/min, P = 0.04). Glucose area under the curve (AUC) was not different between treatments after drink ingestion (GTE = 1,067 ± 133 vs. PLA = 1,052 ± 91 mM/180 min, P = 0.91). Insulin AUC was lower after GTE vs. PLA (5,673 ± 2,153 vs. 7,039 ± 2,588 µIU/180 min, P = 0.05), despite similar rates of glucose appearance (GTE = 0.42 ± 0.16 vs. PLA = 0.43 ± 0.13 g/min, P = 0.74) and disappearance (GTE = 0.43 ± 0.14 vs. PLA = 0.44 ± 0.14 g/min, P = 0.57). We conclude that short-term GTE supplementation did not affect glucose kinetics following ingestion of an oral glucose load postexercise; however, GTE was associated with attenuated insulinemia. These findings suggest GTE lowers the insulin required for a given glucose load during postexercise recovery, which warrants further mechanistic studies in humans. Copyright © 2016 the American Physiological Society.

Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism

International Nuclear Information System (INIS)

Castellino, P.; Luzi, L.; Del Prato, S.; DeFronzo, R.A.

1990-01-01

The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: (1) euglycemic insulin clamp (+80 microU/ml), (2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, (3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and (4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that (1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; (2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; (3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; (4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and (5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism

Fever is not responsible for the elevated glucose kinetics in sepsis

International Nuclear Information System (INIS)

Lang, C.H.; Bagby, G.J.; Blakesley, H.L.; Spitzer, J.J.

1987-01-01

Previous studies have suggested that alterations in the classical neuroendocrine system may not be responsible for the increased glucose metabolism observed during hypermetabolic sepsis. The purpose of the present study was to determine whether inhibition of the cyclooxygenase pathway with indomethacin, which prevents the production of arachidonic acid metabolites by this pathway and the sepsis-induced increase in body temperature, would abolish the increases in glucose appearance (Ra), recycling, and hyperlactacidemia. Sepsis was induced in chronically catheterized conscious rats by multiple injections of live Escherichia coli via a subcutaneous catheter. Septic animals received iv injections of indomethacin every 6-8 hr to block the cyclooxygenase pathway. Glucose kinetics were assessed in 24-hr fasted rats using a constant iv infusion of [6- 3 H]- and [U- 14 C] glucose. Treatment with indomethacin prevented the 1-2 0 C increase in body temperature observed in septic animals. Septic rats exhibited an elevated plasma lactate concentration and increased rates of glucose appearance and recycling. The sepsis-induced alterations in these variables were not attenuated by indomethacin. These results suggest that neither elevated body temperature nor the generation of arachidonic acid metabolites of the cyclooxygenase pathway is responsible for increasing glucose production in hypermetabolic septic rats

Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

DEFF Research Database (Denmark)

Meier, Juris J; Weyhe, Dirk; Michaely, Mark

2004-01-01

of GLP-1 (1.2 pmol x kg x min) and placebo over 8 hrs, each administered in randomized order in the fasting state. C-reactive protein concentrations of 4.9+/-4.2 mg/dL indicated a systemic inflammation. Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon...... practicability and the risk of hypoglycemia. Therefore, the glucose-lowering effect of the incretin hormone glucagon-like peptide 1 (GLP-1) was investigated in patients with type 2 diabetes after major surgery. DESIGN: Randomised clinical study. SETTING: A surgical unit of a university hospital. PATIENTS......, and GLP-1 (specific immunoassays). Statistics were done with repeated-measures analysis of variance and Duncan's post hoc tests. MAIN RESULTS: During the intravenous infusion of GLP-1, plasma glucose concentrations were significantly lowered, reaching the normoglycemic fasting glucose range within 150...

Metabolism in compensatory growth: VI. Effect of energy yielding substrates

Directory of Open Access Journals (Sweden)

Prapti Mahyudi

2002-03-01

Full Text Available An experiment was designed to investigate the effect of different rates of glucose infusion into animals fed a maintenance diet supplemented with undegraded protein (HCHO-casein. Twelve Merino wether Iambs were divided into 3 treatment groups receiving different rates of glucose infusion, 10 mmolelh, 20 mmolelh and 30 mmolelh. The intake and digestibility of dry matter were not affected by glucose infusion. The infusion of glucose increased N retention by reducing both faecal and urinary N. It was estimated that per unit of glucose infused, animal retained 0.15 g N/mmole glucoselh. The efficiency of N retention were 28%, 35% and 44% for glucose infusion rate of 10 mmolelh, 20 mmolelh and 30 mmolelh respectively. Urea entry rate decreased as glucose infusion rate increased. The estimation of protein spared by glucose infusion calculated from N retention and urinary excretion rate gave a value of 20 g and 25 g per 100 g glucose infused respectively. The proportion of glucose entry rate (GER that could potentially derived from amino acids reduced as the rate of glucose infusion increased, being 21%, 17% and 14% for 10 mmolelh, 20 mmolelh and 30 mmolelh of glucose infused respectively. The GER, percentage of glucose oxidized and its contribution to CO2 production increased as the rate of glucose infusion increased. However, CO2 entry rate was not significantly affected by rates of glucose infusion. Glucose uptake by the hind-limb muscles increased with increasing rates of glucose infusion and strongly related with both GER and plasma insulin concentration. There was a tendency for circulating essential amino acids to reduce as the rate of glucose infusion increased, and was more prominent for branched chain amino acids (BCAA at 30 mmolelh of glucose infusion. The reduction of amino acids in the blood circulation occurred concurrently with the reduction in plasma urea concentration and urea entry rate indicated increased net incorporation of amino

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

Science.gov (United States)

Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects.

Science.gov (United States)

Vahidi, O; Kwok, K E; Gopaluni, R B; Knop, F K

2016-09-01

We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main drawback of the former model was its restriction on the route of glucose entrance to the body which was limited to the intravenous glucose injection. To handle the oral glucose intake, we have added a model of glucose absorption in the gastrointestinal tract to the former model to address the resultant variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization problem. The results show acceptable precision of the estimated model parameters and demonstrate the capability of the model in accurate prediction of the body response during the clinical studies.

Strontium-rubidium infusion pump with in-line dosimetry

International Nuclear Information System (INIS)

Barker, S.L.; Loberg, M.D.

1986-01-01

A strontium-rubidium infusion system is described which consists of: (a) means for generating rubidium 82 in a solution which can be infused into a patient; (b) means for infusing the solution into a patient; (c) means for measuring the radioactivity present in the solution as it is infused into the patient; and (d) means for controlling the means for infusing in response to the amount of radioactivity which has been infused into the patient

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

Science.gov (United States)

Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

2017-11-01

Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

The U.S. home infusion market.

Science.gov (United States)

Monk-Tutor, M R

1998-10-01

Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and "isoglycemic" intravenous glucose

DEFF Research Database (Denmark)

Vardarli, Irfan; Arndt, Elisabeth; Deacon, Carolyn F

2014-01-01

,000 mg/day), sitagliptin (100 mg/day), or their combination, on GLP-1 responses and on the incretin effect in 20 patients with type 2 diabetes, comparing an oral glucose challenge (75 g, day 5) and an "isoglycemic" intravenous glucose infusion (day 6). Fasting total GLP-1 was significantly increased...... by metformin and not changed by sitagliptin. After oral glucose, metformin increased and sitagliptin significantly decreased (by 53%) total GLP-1. Fasting and postload intact GLP-1 increased with sitagliptin but not with metformin. After oral glucose, only sitagliptin, but not metformin, significantly...... the numerical contribution of the incretin effect. Insulin secretion with sitagliptin treatment was similarly stimulated with oral and "isoglycemic" intravenous glucose. This points to an important contribution of small changes in incretin concentrations within the basal range or to additional insulinotropic...

Effects of kinins on glucose metabolism in vivo.

Science.gov (United States)

Hartl, W H; Jauch, K W; Wolfe, R R; Schildberg, F W

1990-01-01

Current concepts of the physiological importance of the kinin/prostaglandin system view these tissue factors as part of a defense system, which protects tissues from potentially noxious factors, such as hypoxia or destructive inflammatory reactions. This kinin-triggered defense reaction includes an improvement in cellular energy metabolism. The latter is brought about in peripheral tissues by an increased availability of glucose for anaerobic and aerobic glycolysis, whereas in liver tissue, energy-consuming reactions such as gluconeogenesis are attenuated. There is evidence that such favorable effects can also be produced in man when kinins are administered systemically. Prostaglandins are most likely the second messengers of kinin-induced metabolic effects. Thus, it may be advantageous to increase the availability of kinins either by exogenous infusion or by inhibiting endogenous degradation during postoperative stress or in diseases such as diabetes mellitus, in which glucose metabolism is severely disturbed.

Dextrose boluses versus burette dextrose infusions in prevention of hypoglycemia among preterms admitted at Mulago Hospital: an open label randomized clinical trial.

Science.gov (United States)

Kutamba, E; Lubega, S; Mugalu, J; Ouma, J; Mupere, E

2014-09-01

Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia. We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital. One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) dextrose infusion was computed using 1-RR. From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09-0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63-0.90). Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital. (ClinicalTrials.gov Identifier: NCT01688674).

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes.

Science.gov (United States)

Slattery, David; Choudhary, Pratik

2017-05-01

With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated "insulin-suspend" system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle ® Libre™ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

Science.gov (United States)

Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-01-01

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

No effect of continuous i.p. infusion of bupivacaine on postoperative analgesia, pulmonary function and the stress response to surgery

DEFF Research Database (Denmark)

Scott, N B; Mogensen, T; Greulich, A

1988-01-01

In a double-blind prospective study, 20 patients undergoing major abdominal surgery were allocated randomly to receive a continuous 8-h i.p. infusion of either physiological saline or 0.25% bupivacaine 20 ml h-1 (in saline) following a loading dose of saline 1 ml kg-1 or 0.25% bupivacaine 1 ml kg-1...... was without effect in the management of pain, postoperative pulmonary dysfunction and the stress response in this group of patients....... analogue scale). Postoperative pain, impairment in pulmonary function and increase in serum cortisol and glucose concentrations were not influenced by the i.p. infusion of bupivacaine when compared with saline. This study shows that the i.p. instillation of therapeutically safe doses of bupivacaine...

Glucose kinetics in gluconeogenesis-inhibited rats during rest and exercise

International Nuclear Information System (INIS)

Turcotte, L.P.; Rovner, A.S.; Roark, R.R.; Brooks, G.A.

1990-01-01

To evaluate the role played by gluconeogenesis in blood glucose homeostasis, female Sprague-Dawley rats were injected with mercaptopicolinic acid (MPA), a gluconeogenic inhibitor. Glucose kinetics were assessed by primed, continuous infusion of [U-14C]- and [6(-3)H]glucose via an indwelling jugular catheter at rest and during submaximal exercise at 13.4 m/min on level grade. Blood samples were taken from carotid catheters and analyzed for glucose and lactate concentrations and specific activities. Tissue glycogen samples were obtained from rats after exercise as well as from unexercised animals. When compared with the sham-injected animals, MPA-treated animals had 22% lower (5.92 +/- 0.36 vs. 7.62 +/- 0.21 mM) and 44% higher (1.90 +/- 0.11 vs. 1.32 +/- 0.09 mM) resting arterial glucose and lactate concentrations, respectively. Resting glucose appearance (Ra) rates were 20% lower in the MPA-treated animals (57.2 +/- 7.5 mumol.kg-1.min-1) than in the sham-injected animals (71.1 +/- 12.1 mumol.kg-1.min-1). During exercise, Ra increased to 174.7 +/- 32.8 mumol.kg-1.min-1 in sham-injected animals. In the MPA-treated animals, there was a 35% increase during the first 15 min of exercise, followed by a decrease to the resting values. MPA-treated animals had no measurable glucose recycling at rest or during exercise. Exercise decreased blood glucose concentration (35%) and increased blood lactate concentration (160%) in the MPA-treated animals. Exercising sham-injected animals had increased blood glucose (9.8%) but no change in blood lactate concentration. Moderate depletions in liver and skeletal muscle glycogen contents were observed after exercise

Early mechanism of action of arterially infused ethanol: an experimental study on the influence of infusion speed

International Nuclear Information System (INIS)

Han, Joon Koo

1988-01-01

Abdominal aortography and histopathologic examination after absolute ethanol infusion at fast (0.4cc/sec) and slow speed (0.04cc/sec) were performed on 16 rats (2 controls. 7 fast infusion group. 7 slow infusion group). Angiographic and histopathologic findings were correlated and the findings of slow and fast infusion groups were studied. The results are as follows: 1. Histopathologic findings of the fast infusion group revealed wide area of glomerular and tubular collapses, obliteration of the free space between the Bowmann's capsule and glomerulus, sloughing and loss of the endothelium, fresh thrombi attached to the wall, and cleavage of the muscle layer of the arteries. 2. Angiographic findings of the fast infusion group revealed luminal irregularity, early obstruction of the aorta and the renal arteries, and delayed circulation time. 3. Histopathologic findings of the slow infusion group revealed degenerated, coalesced red blood cell packed in the glomeruli, focal areas of severe glomerular and tubular damage on relatively normal background, endothelial and muscular damage of the arteries. 4. Angiographic findings of the slow infusion group revealed focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but there was no obstruction of the major arteries. 5. In conclusion, author believes that endothelial damage and thrombus formation from the damaged vessel wall, as well as direct cytotoxicity and in situ emboli formation play a significant role in the embolic effect of absolute ethanol.

LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol

DEFF Research Database (Denmark)

Nøhr, Mark K; Dudele, Anete; Poulsen, Morten M

2016-01-01

we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered...... through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b......, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during...

Infusion of butyrate affects plasma glucose, butyrate, and ß-hydroxybutyrate but not plasma insulin in lactating dairy cows

Science.gov (United States)

The objective of this research was to investigate the effects on plasma metabolites and rumen measures when butyrate was infused into the rumen or abomasum of lactating cows. Jugular catheters were inserted into 5 ruminally fistulated Holstein cows (94.2 ± 26.3 days in milk [DIM]; 717 ± 45 kg body w...

Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

Science.gov (United States)

do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

2011-05-01

Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

21 CFR 880.5725 - Infusion pump.

Science.gov (United States)

2010-04-01

... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and...

Beneficial effect of nitrates on myocardial glucose utilization in unstable angina pectoris

International Nuclear Information System (INIS)

Araujo, L.I.; Camici, P.; Spinks, T.; Jones, T.; Maseri, A.

1987-01-01

Myocardial uptake of the glucose analog F-18-2-fluoro-2-deoxy-D-glucose (FDG) was assessed by positron emission tomography in 6 normal volunteers, 7 patients with chronic stable angina and 22 patients with unstable angina at rest in fasting conditions. Regional myocardial perfusion was assessed by rubidium-82. The study was repeated a few days later after intravenous infusion of isosorbide dinitrate. FDG uptake was similar in control subjects and patients with stable angina (0.023 +/- 0.032 vs 0.012 +/- 0.008 mol/ml/min, p less than 0.42) but was about 4-fold higher on the average in patients with unstable angina (0.084 +/- 0.047, p less than 0.01). The severity of coronary obstructions in stable and unstable angina patients was similar. The increased uptake involved the whole heart, including areas not distal to critically stenosed vessels; it was not associated with reduced myocardial perfusion and was not related to a recent episode of transient ischemia as assessed by symptoms and by Holter monitoring. After continuous infusion of nitrates, FDG uptake was consistently and significantly reduced toward normal levels both in areas perfused by critically stenosed coronary arteries and by noncritically stenosed vessels

Effects of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis

DEFF Research Database (Denmark)

Larsen, Mogens; Røntved, Christine Maria; Theil, Peter Kappel

2017-01-01

The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL......) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at –14, +4, +15, and +29 DRTC by measuring [13C]Phe isotopic...... enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[13C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [125I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [13C...

Continuous glucose monitoring in acute coronary syndrome.

Science.gov (United States)

Rodríguez-Quintanilla, Karina Alejandra; Lavalle-González, Fernando Javier; Mancillas-Adame, Leonardo Guadalupe; Zapata-Garrido, Alfonso Javier; Villarreal-Pérez, Jesús Zacarías; Tamez-Pérez, Héctor Eloy

2013-01-01

Diabetes mellitus is an independent risk factor for cardiovascular disease. To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters: time to achieve normoglycemia, period of time in normoglycemia, and episodes of hypoglycemia. We performed a pilot, non-randomized, unblinded clinical trial that included 16 patients with acute coronary artery syndrome, a capillary or venous blood glucose ≥ 140 mg/dl, and treatment with a continuous infusion of fast acting human insulin. These patients were randomized into 2 groups: a conventional group, in which capillary measurement and recording as well as insulin adjustment were made every 4h, and an intervention group, in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system. Student's t-test was applied for mean differences and the X(2) test for qualitative variables. We observed a statistically significant difference in the mean time for achieving normoglycemia, favoring the conventional group with a P = 0.02. Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion.

Science.gov (United States)

Garcia, Jowell; Garg, Alka; Song, Yunmei; Fotios, Ambados; Andersen, Chad; Garg, Sanjay

2018-01-01

There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid

Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition

Directory of Open Access Journals (Sweden)

Isabel Arrieta-Cruz

2016-02-01

Full Text Available Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH. In the early stages, all branched-chain amino acids (BCAA are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance.

Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

Science.gov (United States)

Wasserman, Michael J; Weber, Deborah A; Guthrie, Judith A; Bykerk, Vivian P; Lee, Peter; Keystone, Edward C

2004-10-01

We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia.

Science.gov (United States)

Ibrahim, Mohamed M; Tammam, Tarek Fouad; Ebaed, Mohy El Deen; Sarhan, Hatem A; Gad, Gamal F; Hussein, Amal K

2017-01-01

Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem). This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30-60 min. This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2 years. One hundred and eighty-seven patients were enrolled on it. This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30-60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180 min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20. The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay. The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study. The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP.

Understanding Infusion Pumps.

Science.gov (United States)

Mandel, Jeff E

2018-04-01

Infusion systems are complicated electromechanical systems that are used to deliver anesthetic drugs with moderate precision. Four types of systems are described-gravity feed, in-line piston, peristaltic, and syringe. These systems are subject to a number of failure modes-occlusion, disconnection, siphoning, infiltration, and air bubbles. The relative advantages of the various systems and some of the monitoring capabilities are discussed. A brief example of the use of an infusion system during anesthetic induction is presented. With understanding of the functioning of these systems, users may develop greater comfort.

On the role of glucose-dependent insulintropic polypeptide in postprandial metabolism in humans

DEFF Research Database (Denmark)

Asmar, Meena; Tangaa, Winnie; Madsbad, Sten

2010-01-01

infusion of GIP (0.8 pmol.kg(-1).min(-1)) or saline for 300 min during and after a fixed meal (protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males......, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen in the plasma TAG on Intralipid + GIP/saline and Intralipid + glucose + GIP/saline days. FFA concentrations were lower on Intralipid + glucose + GIP/saline days (P saline...... days and on Intralipid + GIP day (P saline day. Insulin increased on all GIP days compared with saline days (P

Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections.

Science.gov (United States)

Holmes-Walker, Deborah Jane; Gunton, Jenny E; Hawthorne, Wayne; Payk, Marlene; Anderson, Patricia; Donath, Susan; Loudovaris, Tom; Ward, Glenn M; Kay, Thomas Wh; OʼConnell, Philip J

2017-06-01

The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia. This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4). After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0). In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.

Model-based closed-loop glucose control in type 1 diabetes

DEFF Research Database (Denmark)

Schmidt, Signe; Boiroux, Dimitri; Duun-Henriksen, Anne Katrine

2013-01-01

To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific parameters......: insulin sensitivity factor, insulin action time, and basal insulin infusion rate. The stochastic part is identical for all patients but identified from data from a single patient. Results of the first clinical feasibility test of the algorithm are presented....

Swelling and infusion of tea in tea bags.

Science.gov (United States)

Yadav, Geeta U; Joshi, Bhushan S; Patwardhan, Ashwin W; Singh, Gurmeet

2017-07-01

The present study deals with swelling and infusion kinetics of tea granules in tea bags. The swelling and infusion kinetics of tea bags differing in tea loading and tea bag shapes were compared with loose tea. Increment in temperature and dipping frequency of tea bag in hot water increased the infusion kinetics of tea bags. Reduction in particle size enhanced the swelling and infusion kinetics of tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading of tea granules in tea bag and tea bag shapes on infusion kinetics were investigated. Increase in tea loading in tea bags resulted in reduced infusion kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed the lowest kinetics, amongst the various bags studied. The swelling and infusion kinetics of loose tea was always faster and higher than that of tea bags. It was found that overall effect of percentage filling of tea granules and height of tea bed in a tea bag affects tea infusion kinetics the most. Weibull model was found to be in good agreement with the swelling data.

Effects of vanadium supplementation on performance, some plasma metabolites and glucose metabolism in Mahabadi goat kids.

Science.gov (United States)

Zarqami, A; Ganjkhanlou, M; Zali, A; Rezayazdi, K; Jolazadeh, A R

2018-04-01

This experiment was conducted to investigate the effects of vanadium (V) supplementation on performance, some plasma metabolites (cholesterol and triglycerides) and glucose metabolism in Mahabadi goat kids. Twenty-eight male kids (15 ± 2 kg body weight) were fed for 14 weeks in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 1, 2, and 3 mg V as vanadyl sulfate/animal/daily. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. Dry matter intake did not change by V supplementation, but adding V quadraticaly improved feed efficiency (p = .03) and tended to increase average daily gain (Quadratic, p = .09). Blood metabolites were unaffected by V supplementation, except for concentration of glucose in plasma, which decreased linearly as supplemental V level increased (p = .02). Plasma glucose concentrations at 15, 30, 45 and 60 min after glucose infusion were decreased in a quadratic fashion in response to increasing supplemental V level (p kids supplemented with 2 mg V had higher glucose clearance rate (K) and lower glucose half-life (T ½ ; p kids. © 2017 Blackwell Verlag GmbH.

Static output feedback ℋ ∞ control for a fractional-order glucose-insulin system

KAUST Repository

N’Doye, Ibrahima

2015-05-23

This paper presents the ℋ∞ static output feedback control of nonlinear fractional-order systems. Based on the extended bounded real lemma, the ℋ∞ control is formulated and sufficient conditions are derived in terms of linear matrix inequalities (LMIs) formulation by using the fractional Lyapunov direct method where the fractional-order α belongs to 0 < α < 1. The control approach is finally applied to the regulation of the glucose level in diabetes type 1 treatment. Therefore, it is attempted to incorporate fractional-order into the mathematical minimal model of glucose-insulin system dynamics and it is still an interesting challenge to show, how the order of a fractional differential system affects the dynamics of the system in the presence of meal disturbance. Numerical simulations are carried out to illustrate our proposed results and show that the nonlinear fractional-order glucose-insulin systems are, at least, as stable as their integer-order counterpart in the presence of exogenous glucose infusion or meal disturbance. © 2015 Institute of Control, Robotics and Systems and The Korean Institute of Electrical Engineers and Springer-Verlag Berlin Heidelberg

Central infusion of leptin improves insulin resistance and suppresses beta-cell function, but not beta-cell mass, primarily through the sympathetic nervous system in a type 2 diabetic rat model.

Science.gov (United States)

Park, Sunmin; Ahn, Il Sung; Kim, Da Sol

2010-06-05

We investigated whether hypothalamic leptin alters beta-cell function and mass directly via the sympathetic nervous system (SNS) or indirectly as the result of altered insulin resistant states. The 90% pancreatectomized male Sprague Dawley rats had sympathectomy into the pancreas by applying phenol into the descending aorta (SNSX) or its sham operation (Sham). Each group was divided into two sections, receiving either leptin at 300ng/kgbw/h or artificial cerebrospinal fluid (aCSF) via intracerebroventricular (ICV) infusion for 3h as a short-term study. After finishing the infusion study, ICV leptin (3mug/kg bw/day) or ICV aCSF (control) was infused in rats fed 30 energy % fat diets by osmotic pump for 4weeks. At the end of the long-term study, glucose-stimulated insulin secretion and islet morphometry were analyzed. Acute ICV leptin administration in Sham rats, but not in SNSX rats, suppressed the first- and second-phase insulin secretion at hyperglycemic clamp by about 48% compared to the control. Regardless of SNSX, the 4-week administration of ICV leptin improved glucose tolerance during oral glucose tolerance tests and insulin sensitivity at hyperglycemic clamp, compared to the control, while it suppressed second-phase insulin secretion in Sham rats but not in SNSX rats. However, the pancreatic beta-cell area and mass were not affected by leptin and SNSX, though ICV leptin decreased individual beta-cell size and concomitantly increased beta-cell apoptosis in Sham rats. Leptin directly decreases insulin secretion capacity mainly through the activation of SNS without modulating pancreatic beta-cell mass.

Infusion's greenfield subsidiary in Poland

NARCIS (Netherlands)

Williams, C.; van Eerde, W.; The, D.

2012-01-01

The president of Infusion Development Corporation was reviewing the progress of the new subsidiary the company had set up 15 months earlier in Krakow, Poland. The purpose of the subsidiary was to work with other Infusion offices around the world to provide innovative software development services to

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

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Vivi F. H. Jensen

2017-01-01

Full Text Available The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls. The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

Science.gov (United States)

Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

2016-08-01

Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC 24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both

Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus

DEFF Research Database (Denmark)

Torekov, Signe Sørensen; Holst, J J; Ehlers, M R

2014-01-01

(7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes. METHODS: We compared the efficacy and safety of three doses of recombinant GLP-1, ranging from 1.25 to 5.0 pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3...... months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control. RESULTS: The mean decreases in HbA1c at endpoint (week 12) were significantly greater for all three rGLP-1...... dose groups when each was compared with the placebo group, with the greatest decrease occurring in the 5.0 pkm dose group (-1.3%, s.d. ± 0.18, p fasting plasma glucose from baseline to endpoint were significantly greater for all three rGLP-1 dose groups than...

Pharmacokinetics and toxicology of continuously infused nitroimidazoles

International Nuclear Information System (INIS)

Eifel, P.J.; Brown, J.M.

1984-01-01

The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

MONITORING TETESAN INFUS BERBASIS MIKROKONTROLER ATMEGA16

Directory of Open Access Journals (Sweden)

Ardiyanto Iqbal Nugroho

2015-09-01

Penelitian ini menghasilkan suatu alat monitoring tetesan infus yang dapat memberikan informasi mengenai laju kecepatan tetesan dan kondisi cairan pada infus. Sistem yang secara realtime dimonitoring oleh perawat ini dapat mengurangi permasalahan yang timbul karena kelalaian petugas. Sehingga perawat tidak secara manual dalam mengatur kecepatan tetesan infus dan meningkatkan pelayanan kepada pasien.

TCPTP Regulates Insulin Signalling in AgRP Neurons to Coordinate Glucose Metabolism with Feeding.

Science.gov (United States)

Dodd, Garron T; Lee-Young, Robert S; Brüning, Jens C; Tiganis, Tony

2018-04-30

Insulin regulates glucose metabolism by eliciting effects on peripheral tissues as well as the brain. Insulin receptor (IR) signalling inhibits AgRP-expressing neurons in the hypothalamus to contribute to the suppression of hepatic glucose production (HGP) by insulin, whereas AgRP neuronal activation attenuates brown adipose tissue (BAT) glucose uptake. The tyrosine phosphatase TCPTP suppresses IR signalling in AgRP neurons. Hypothalamic TCPTP is induced by fasting and degraded after feeding. Here we assessed the influence of TCPTP in AgRP neurons in the control of glucose metabolism. TCPTP deletion in AgRP neurons ( Agrp -Cre; Ptpn2 fl/fl ) enhanced insulin sensitivity as assessed by the increased glucose infusion rates and reduced HGP during hyperinsulinemic-euglycemic clamps, accompanied by increased [ 14 C]-2-deoxy-D-glucose uptake in BAT and browned white adipose tissue. TCPTP deficiency in AgRP neurons promoted the intracerebroventricular insulin-induced repression of hepatic gluconeogenesis in otherwise unresponsive food-restricted mice yet had no effect in fed/satiated mice where hypothalamic TCPTP levels are reduced. The improvement in glucose homeostasis in Agrp -Cre; Ptpn2 fl/fl mice was corrected by IR heterozygosity ( Agrp -Cre; Ptpn2 fl/fl ; Insr fl/+ ), causally linking the effects on glucose metabolism with the IR signalling in AgRP neurons. Our findings demonstrate that TCPTP controls IR signalling in AgRP neurons to coordinate HGP and brown/beige adipocyte glucose uptake in response to feeding/fasting. © 2018 by the American Diabetes Association.

Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis

DEFF Research Database (Denmark)

Vilstrup, Hendrik; Gluud, C; Hardt, F

1990-01-01

We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients...

Glucose pump test can be used to measure blood flow rate of native arteriovenous fistula in chronic hemodialysis.

Science.gov (United States)

Yavuz, Y C; Selcuk, N Y; Altıntepe, L; Güney, I; Yavuz, S

2018-01-01

In chronic hemodialysis patients, the low flow of vascular access may leads to inadequate dialysis, increased rate of hospitalization, morbidity, and mortality. It was found that surveillance should be performed for native arteriovenous (AV) should not be performed for AV graft in various studies. However, surveillance was done in graft AV fistulas in most studies. Doppler ultrasonography (US) was suggested for surveillance of AV fistulas by the last vascular access guideline of National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI). The aim of study is to determine whether glucose pump test (GPT) is used for surveillance of native AV fistulas by using Doppler US as reference. In 93 chronic hemodialysis patients with native AV fistula, blood flow rates were measured by Doppler US and GPT. For GPT, glucose was infused to 16 mL/min by pump and was measured at basal before the infusion and 11 s after the start of the infusion by glucometer. Doppler US was done by an expert radiologist. Used statistical tests were Mann-Whitney U test, Friedman test, regression analysis, and multiple regression analysis. Median values of blood flow rates measured by GPT (707 mL/min) and by Doppler US (700 mL/min) were not different (Z = 0.414, P = 0.678). Results of GPT and Doppler US measurements were positive correlate by regression analysis. The mean GPT value of diabetic patients (n = 39; 908 mL/min) was similar to that of nondiabetic patients (n = 54; 751 mL/min; Z = 1.31, P = 0.188). GPT values measured at three different dialysis session did not differ from each other that by Friedman test (F = 0.92, P = 0.39). This showed that GPT was stable and reliable. Glucose pump test can be used to measure blood flow rate of native AV fistula. GPT is an accurate and reliable test.

Evaluation of an adult insulin infusion protocol at an academic medical center.

Science.gov (United States)

Petrov, Katerina I; Burns, Tammy L; Drincic, Andjela

2012-05-01

Acknowledging evidence of possible detrimental effects of tightly controlled blood glucose levels, the American Association of Clinical Endocrinologists and the American Diabetes Association published a consensus statement recommending less strict control for most diabetic patients. As a result of these recommendations, our academic center at Creighton University Medical Center revised its adult insulin infusion protocol to target blood glucose levels ranging from 120 to 180 mg/dL for regular (standard) glycemic control and 80 to 120 mg/dL for tight control; previous targets had ranged from 80 to 180 mg/dL and 70 to 110 mg/dL, respectively. The primary objective was to evaluate the time that blood glucose values were within the target range for patients receiving the new protocol, compared with patients receiving the previous protocol. Our study was designed to evaluate the effectiveness and safety of the revised protocol. Using a retrospective chart review, we collected data for 4 months from patients on the old insulin protocol (May to August 2009) and for 4 months from patients on the new protocol (September to December 2009). Secondary endpoints included the number of hypoglycemic episodes (blood glucose below 70 mg/dL) and severe hypoglycemic episodes (blood glucose 40 mg/dL or lower) experienced by patients receiving the new insulin protocol compared with those receiving the former protocol. Patient characteristics were similar at baseline. Blood glucose values stayed within the target range for a significantly shorter time with the new protocol than with the former protocol (44.6% vs. 56.8%, respectively; P protocol. No statistically significant differences in hypoglycemia were observed after the protocol was changed. Hypoglycemia occurred in 31% of the former-protocol patients compared with 18% of the revised-protocol patients. Severe hypoglycemia was experienced by 2.1% of patients on the old protocol and by 3.1% of patients on the new protocol. Rates of

Blood glucose control in the intensive care unit: benefits and risks.

Science.gov (United States)

Gunst, Jan; Van den Berghe, Greet

2010-01-01

Abnormal blood glucose levels are common during critical illness and are associated with outcomes that correspond to a J-shaped curve, the lowest risk associated with normoglycemia. Three proof-of-concept randomized-controlled-trials performed in the surgical, medical, and pediatric intensive care units of the Leuven University Hospital in Belgium demonstrated that maintaining strict age-adjusted normal fasting levels of glycemia (80-110 mg/dl in adults, 70-100 mg/dl in children, 50-80 mg/dl in infants) with intensive insulin therapy reduced morbidity and mortality as compared with tolerating stress hyperglycemia as a potentially beneficial response. Recently, concern has risen about the safety of this intervention, as a multicenter adult study reported an, as yet unexplained, increased mortality with targeting normoglycemia as compared with an intermediate blood glucose level of around 140 mg/dl. This apparent contradiction may be explained by several methodological differences among studies, comprising, among others, different glucose target ranges in the control groups, different feeding policies, and variable accuracy of tools used for glucose measurement and insulin infusion. Hence, efficacy and safety of intensive insulin therapy may be affected by patient-related and ICU setting-related variables. Therefore, no single optimal blood glucose target range for ICU patients can be advocated. It appears safe not to embark on targeting "age-normal" levels in intensive care units (ICUs) that are not equipped to accurately and frequently measure blood glucose, and have not acquired extensive experience with intravenous insulin administration using a customized guideline. A simple fallback position could be to control blood glucose levels as close to normal as possible without evoking unacceptable blood glucose fluctuations, hypoglycemia, and hypokalemia.

The acute effect of metformin on glucose production in the conscious dog is primarily attributable to inhibition of glycogenolysis.

Science.gov (United States)

Chu, C A; Wiernsperger, N; Muscato, N; Knauf, M; Neal, D W; Cherrington, A D

2000-12-01

Although metformin has been used worldwide to treat type 2 diabetes for several decades, its mechanism of action on glucose homeostasis remains controversial. To further assess the effect of metformin on glucose metabolism, 10 42-hour-fasted conscious dogs were studied in the absence ([Con] n = 5) and presence ([Met] n = 5) of a portal infusion of metformin (0.15 mg x kg(-1) x min(-1)) over 300 minutes. Hepatic glucose production was measured by both arteriovenous-difference and tracer methods. All dogs were maintained on a pancreatic clamp and in a euglycemic state to ensure that any changes in glucose metabolism would result directly from the effects of metformin. The arterial metformin level was 21 +/- 3 microg/mL during the test period. Net hepatic glucose output (NHGO) decreased in Met dogs from 1.9 +/- 0.2 to 0.7 +/- 0.1 mg x kg(-1) x min(-1) (P metformin on glucose metabolism was an inhibition of hepatic glucose production and not a stimulation of glucose utilization; and (2) the inhibition of glucose production was attributable to a decrease in hepatic glycogenolysis and not to an alteration in gluconeogenic flux.

Infusing PDA technology into nursing education.

Science.gov (United States)

White, Ann; Allen, Patricia; Goodwin, Linda; Breckinridge, Daya; Dowell, Jeffery; Garvy, Ryan

2005-01-01

Use of the personal digital assistant (PDA) has been infused into the accelerated baccalaureate program at Duke University to help prepare nursing students for professional practice. The authors provide an overview of the use of PDAs in the classroom, laboratory, and clinical setting. Technical aspects of PDA infusion and steps to ensure regulatory compliance are explored. Benefits of PDA use by both faculty and students in the program and challenges met with the infusion of this technology are also described.

Assessment of quality of glycemic control in intensive care patients treated with an insulin infusion at a teaching hospital.

Science.gov (United States)

Gauthier, Lyne; Ferguson, Jessica; Dubé, Anne-Isabelle; Nguyen, Patrick Viet-Quoc; Beauchesne, Marie-France; Boutin, Jean-Marie

2014-04-01

To describe the quality of glycemic control in patients in intensive care units (ICUs) treated with an intravenous (IV) insulin infusion at a teaching hospital. This retrospective study included patients admitted to the ICU and treated with an IV insulin infusion for at least 12 h between August 1 and November 30, 2011. Medical charts were reviewed. The primary quality indicator for glycemic control was the mean percent of blood glucose values per patient in the 6.1 to 8 mmol/L target range. A total of 351 patients were included; 61.5% of subjects had no known diabetes. Admissions were mainly for surgery (61.3%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16.8±7.3. The mean percent of blood glucose values per patient in the 6.1 to 8 mmol/L range was 35% for all subjects and 26.2% for patients with diabetes. If a target of 6.1 to 10 mmol/L was considered, those values became 63% and 54.6%. At least 1 episode of hyperglycemia (>10 mmol/L), hypoglycemia (quality of glycemic control in patients in the ICU at our hospital needs to be improved. A new computerized IV insulin protocol is currently being tested. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Quantitative kinetics of renal glucose metabolism by the isotope dilution method in the unanesthetized sheep

International Nuclear Information System (INIS)

Sasaki, Shin-ichi; Watanabe, Yasukuni; Ambo, Kaichi; Tsuda, Tsuneyuki.

1982-01-01

Renal glucose production and utilization rates in normal fed and fasted sheep were determined by the measurements of renal blood flow and arteriovenous 14 C-glucose and glucose concentration differences using the method of primed continuous infusion of u- 14 C-glucose. At the same time total body glucose turnover rate was measured, and the contribution of renal glucose production to glucose requirement in the whole animal was quantitatively estimated. The renal blood flow for fed and fasted sheep were 20 +- 1 and 20 +- 3 ml/min/kg, respectively. No significant difference in the renal blood flow existed between the groups. The total body glucose turnover rate in fasted sheep (1.68 +- 0.20 mg/min/kg) was significantly lowered (P < 0.01) than that of fed sheep (2.20 +- 0.13 mg/min/kg). The renal glucose production rate in fed sheep was 0.47 +- 0.05 mg/min/kg and this rate accounted for about 21.4% of the glucose turnover rate. The renal glucose production rate in fasted sheep decreased to about 45% of that in fed sheep. However, the renal glucose utilization rate was similar in fed (0.26 +- 0.04 mg/min/kg) and fasted sheep (0.27 +- 0.04 mg/min/kg). Net renal glucose production rate in fed sheep, which was measured by the method of arteriovenous glucose concentration differences, was 0.22 +- 0.05 mg/min/kg, but that in fasted sheep was a negative value. These results suggest that the kidney of ruminant seems to produce a significant amount of glucose and to utilize it simultaneously with production. (author)

Comparative Simulation Study of Glucose Control Methods Designed for Use in the Intensive Care Unit Setting via a Novel Controller Scoring Metric.

Science.gov (United States)

DeJournett, Jeremy; DeJournett, Leon

2017-11-01

Effective glucose control in the intensive care unit (ICU) setting has the potential to decrease morbidity and mortality rates and thereby decrease health care expenditures. To evaluate what constitutes effective glucose control, typically several metrics are reported, including time in range, time in mild and severe hypoglycemia, coefficient of variation, and others. To date, there is no one metric that combines all of these individual metrics to give a number indicative of overall performance. We proposed a composite metric that combines 5 commonly reported metrics, and we used this composite metric to compare 6 glucose controllers. We evaluated the following controllers: Ideal Medical Technologies (IMT) artificial-intelligence-based controller, Yale protocol, Glucommander, Wintergerst et al PID controller, GRIP, and NICE-SUGAR. We evaluated each controller across 80 simulated patients, 4 clinically relevant exogenous dextrose infusions, and one nonclinical infusion as a test of the controller's ability to handle difficult situations. This gave a total of 2400 5-day simulations, and 585 604 individual glucose values for analysis. We used a random walk sensor error model that gave a 10% MARD. For each controller, we calculated severe hypoglycemia (140 mg/dL), and coefficient of variation (CV), as well as our novel controller metric. For the controllers tested, we achieved the following median values for our novel controller scoring metric: IMT: 88.1, YALE: 46.7, GLUC: 47.2, PID: 50, GRIP: 48.2, NICE: 46.4. The novel scoring metric employed in this study shows promise as a means for evaluating new and existing ICU-based glucose controllers, and it could be used in the future to compare results of glucose control studies in critical care. The IMT AI-based glucose controller demonstrated the most consistent performance results based on this new metric.

The effect of glucagon on infusion cholangiography

International Nuclear Information System (INIS)

Evans, A.F.; Whitehouse, G.H.

1979-01-01

An assessment has been made of the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min -1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min -1 over 30 min. Radiographs were taken in both series immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series then assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography. (author)

Discrete Blood Glucose Control in Diabetic Göttingen Minipigs

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Berno J.E. Misgeld

2016-07-01

Full Text Available Despite continuous research effort, patients with type 1 diabetes mellitus (T1D experience difficulties in daily adjustments of their blood glucose concentrations. New technological developments in the form of implanted intravenous infusion pumps and continuous blood glucose sensors might alleviate obstacles for the automatic adjustment of blood glucose concentration. These obstacles consist, for example, of large time-delays and insulin storage effects for the subcutaneous/interstitial route. Towards the goal of an artificial pancreas, we present a novel feedback controller approach that combines classical loop-shaping techniques with gain-scheduling and modern H ∞ -robust control approaches. A disturbance rejection design is proposed in discrete frequency domain based on the detailed model of the diabetic Göttingen minipig. The model is trimmed and linearised over a large operating range of blood glucose concentrations and insulin sensitivity values. Controller parameters are determined for each of these operating points. A discrete H ∞ loop-shaping compensator is designed to increase robustness of the artificial pancreas against general coprime factor uncertainty. The gain scheduled controller uses subcutaneous insulin injection as a control input and determines the controller input error from intravenous blood glucose concentration measurements, where parameter scheduling is achieved by an estimator of the insulin sensitivity parameter. Thus, only one controller stabilises a family of animal models. The controller is validated in silico with a total number of five Göttingen Minipig models, which were previously obtained by experimental identification procedures. Its performance is compared with an experimentally tested switching PI-controller.

Pulsatile versus steady infusions for hepatic artery chemotherapy

International Nuclear Information System (INIS)

Kim, E.E.; Haynie, T.P.; Wright, K.C.; Chaynsangavej, C.; Gianturco, C.; Lamki, L.; Wallace, S.

1984-01-01

Hepatic artery chemotherapy for unresectable liver tumors requires an even distribution of the drugs in the tumor or vascular bed. This cannot be determined angiographically because the drugs are infused at a much lower rate than the contrast media. It is easy, however, to determine the quality of the perfusion by injecting a small volume of Tc-99m MAA in one of the side ports while chemotherapeutic agent is being infused at the same rate. Usually this shows a uniform, satisfactory distribution of isotope. Occasionally, however, some areas fail to receive Tc-99m in spite of what appears to be a good position of the catheter tip. Since ''streaming'' of the infused drugs has been blamed for their uneven distribution, the authors decided to compare the usual steady flow infusions with infusions made pulsatile by the addition of a pulsing device (Gianturco Pump) attached to the infusion tubing. Eighty-three patients were studied with steady as well as pulsatile infusions. In 16 of these patients the perfusion pattern was definitely changed by the pulsatile infusion. In one patient the pulsatile mode resulted in an unwanted gastric perfusion. In 5 patients the distribution was improved in one hepatic lobe and in 10 patients it was improved in both lobes. These results show that hepatic artery perfusions can occasionally be improved by pulsing the infusate. However, pulsing can produce the unwanted perfusion of extra-hepatic areas

The Diabetes Assistant: A Smartphone-Based System for Real-Time Control of Blood Glucose

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Patrick Keith-Hynes

2014-11-01

Full Text Available Type 1 Diabetes Mellitus (T1DM is an autoimmune disease in which the insulin-producing beta cells of the pancreas are destroyed and insulin must be injected daily to enable the body to metabolize glucose. Standard therapy for T1DM involves self-monitoring of blood glucose (SMBG several times daily with a blood glucose meter and injecting insulin via a syringe, pen or insulin pump. An “Artificial Pancreas” (AP is a closed-loop control system that uses a continuous glucose monitor (CGM, an insulin pump and an internal algorithm to automatically manage insulin infusion to keep the subject’s blood glucose within a desired range. Although no fully closed-loop AP systems are currently commercially available there are intense academic and commercial efforts to produce safe and effective AP systems. In this paper we present the Diabetes Assistant (DiAs, an ultraportable AP research platform designed to enable home studies of Closed Loop Control (CLC of blood glucose in subjects with Type 1 Diabetes Mellitus. DiAs consists of an Android (Google Inc., Mountain View, CA, USA smartphone equipped with communication, control and user interface software wirelessly connected to a continuous glucose monitor and insulin pump. The software consists of a network of mobile applications with well-defined Application Programming Interfaces (APIs running atop an enhanced version of Android with non-essential elements removed. CLC and safety applications receive real-time data from the CGM and pump, estimate the patient’s metabolic state and risk of hypo- and hyperglycemia, adjust the insulin infusion rate, raise alarms as needed and transmit de-identified data to a secure remote server. Some applications may be replaced by researchers wishing to conduct outpatient ambulatory studies of novel Closed Loop Control, Safety or User Interface modules. Over the past three years the DiAs platform has been used in a series of AP clinical trials sponsored by the National

Liquid-liquid displacement in slippery liquid-infused membranes (SLIMs)

OpenAIRE

Bazyar, Hanieh; Lv, Pengyu; Wood, Jeffery A.; Porada, Slawomir; Lohse, Detlef; Lammertink, Rob G. H.

2018-01-01

Liquid-infused membranes inspired by slippery liquid-infused porous surfaces (SLIPS) have been recently introduced to membrane technology. The gating mechanism of these membranes is expected to give rise to anti-fouling properties and multi-phase transport capabilities. However, the long-term retention of the infusion liquid has not yet been explored. To address this issue, we investigate the retention of the infusion liquid in slippery liquid-infused membranes (SLIMs) via liquid-liquid displ...

A mathematical model for predicting glucose levels in critically-ill patients: the PIGnOLI model

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Zhongheng Zhang

2015-06-01

Full Text Available Background and Objectives. Glycemic control is of paramount importance in the intensive care unit. Presently, several BG control algorithms have been developed for clinical trials, but they are mostly based on experts’ opinion and consensus. There are no validated models predicting how glucose levels will change after initiating of insulin infusion in critically ill patients. The study aimed to develop an equation for initial insulin dose setting.Methods. A large critical care database was employed for the study. Linear regression model fitting was employed. Retested blood glucose was used as the independent variable. Insulin rate was forced into the model. Multivariable fractional polynomials and interaction terms were used to explore the complex relationships among covariates. The overall fit of the model was examined by using residuals and adjusted R-squared values. Regression diagnostics were used to explore the influence of outliers on the model.Main Results. A total of 6,487 ICU admissions requiring insulin pump therapy were identified. The dataset was randomly split into two subsets at 7 to 3 ratio. The initial model comprised fractional polynomials and interactions terms. However, this model was not stable by excluding several outliers. I fitted a simple linear model without interaction. The selected prediction model (Predicting Glucose Levels in ICU, PIGnOLI included variables of initial blood glucose, insulin rate, PO volume, total parental nutrition, body mass index (BMI, lactate, congestive heart failure, renal failure, liver disease, time interval of BS recheck, dextrose rate. Insulin rate was significantly associated with blood glucose reduction (coefficient: −0.52, 95% CI [−1.03, −0.01]. The parsimonious model was well validated with the validation subset, with an adjusted R-squared value of 0.8259.Conclusion. The study developed the PIGnOLI model for the initial insulin dose setting. Furthermore, experimental study is

Financial analysis for the infusion alliance.

Science.gov (United States)

Perucca, Roxanne

2010-01-01

Providing high-quality, cost-efficient care is a major strategic initiative of every health care organization. Today's health care environment is transparent; very competitive; and focused upon providing exceptional service, safety, and quality. Establishing an infusion alliance facilitates the achievement of organizational strategic initiatives, that is, increases patient throughput, decreases length of stay, prevents the occurrence of infusion-related complications, enhances customer satisfaction, and provides greater cost-efficiency. This article will discuss how to develop a financial analysis that promotes value and enhances the financial outcomes of an infusion alliance.

Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes

Science.gov (United States)

Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C.

2016-01-01

Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, Pprediabetic state. PMID:26999667

Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

Science.gov (United States)

Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

2016-04-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight

DEFF Research Database (Denmark)

Hermann, T S; Rask-Madsen, C; Ihlemann, N

2003-01-01

of acetylcholine and sodium nitroprusside in the forearm of fourteen 21-yr-old men with low birth weight and 16 controls of normal birth weight. Glucose uptake was measured during intraarterial insulin infusion. Dose-response studies were repeated during insulin infusion. The maximal blood flow during......Low birth weight has been linked to insulin resistance and cardiovascular disease. We hypothesized that insulin sensitivity of both muscle and vascular tissues were impaired in young men with low birth weight. Blood flow was measured by venous occlusion plethysmography during dose-response studies...... acetylcholine infusion was 14.1 +/- 2.7 and 14.4 +/- 2.1 [ml x (100 ml forearm)(-1) x min(-1)] in low and normal birth weight subjects, respectively. Insulin coinfusion increased acetylcholine-stimulated flow in both groups: 18.0 +/- 3.1 vs. 17.9 +/- 3.1 [ml x (100 ml forearm)(-1) x min(-1)], NS. Insulin...

Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

Science.gov (United States)

Darlington, Daniel N.; Chew, Gordon; Ha, Taryn; Keil, Lanny C.; Dallman, Mary F.

1990-01-01

Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to

Infusion Antihypoxants in Children with Critical Conditions

Directory of Open Access Journals (Sweden)

Yu. S. Aleksandrovich

2014-01-01

Full Text Available Hypoxia and mitochondrial damage are a key component of the pathogenesis and tanatogenesis of a critical condition, suggesting the need for its prevention and maximally rapid elimination. Objective: to analyze the efficacy and safety of infusion antihypoxants used in critically ill children from the results of researches. Materials and methods. Available investigations dealing with infusion therapy in children and papers on the use of infusion antihypoxants in adults in 2005 to 2013 were sought in the medical databases PubMed and Cochrane Library with their free availability and analyzed. Results. The analysis included 70 trials. The pathophysiology and pathobiochemistry of hypoxia in critically ill children are given; the current principles of its correction by infusion therapy are considered in detail. Particular emphasis is placed on trials evaluating the efficacy and safety of succinic acid solutions in children. Main indications for and contraindications to their use are demonstrated. Conclusion. The use of Krebs cycle substrate-based infusion antihypoxants (malate, succinate is an effective and promising procedure for the intensive therapy and correction of hypoxia in both adults and children with critical conditions. Considering the fact that papers on the use of infusion antihypoxants in children are scanty, there is a need for further investigations. 

Exenatide improves glucocorticoid-induced glucose intolerance in mice

Directory of Open Access Journals (Sweden)

Ruiying Zhao

2011-01-01

Full Text Available Ruiying Zhao1,2*, Enrique Fuentes-Mattei1,2*, Guermarie Velazquez-Torres1,3, Chun-Hui Su1,2, Jian Chen1, Mong-Hong Lee1,2, Sai-Ching Jim Yeung4,51Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Program in Genes and Development, 3Program in Cancer Biology, Graduate School of Biomedical Sciences, University of Texas Health Science Center in Houston, Houston, TX, USA; 4Department of Endocrine Neoplasia and Hormonal Disorders, 5Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA *Both authors contributed equally.Abstract: Exenatide is an incretin mimetic that is recently available in the US for the treatment of diabetes. There is a paucity of information on the effects of exenatide in glucocorticoid (GC-induced diabetes. Although the effect of continuous intravenous infusion of exenatide on GC-induced glucose intolerance has been investigated before in healthy human males receiving oral prednisolone, we investigated the efficacy of a single subcutaneous dose of exenatide (3 µg/kg in lowering blood glucose in GC-induced glucose intolerance in C57BL/6 mice. In a longitudinal experiment, the area under the curve (AUC of oral glucose tolerance tests (OGTT significantly increased after dexamethasone (P = 0.004, which was subsequently decreased by exenatide (P < 0.001. A cross-sectional experiment showed that exenatide improved glucose tolerance compared with placebo in a mouse model of dexamethasone-induced glucose intolerance. AUC of OGTT in the exenatide group were significantly (P < 0.001 lower than in the placebo group. Insulin tolerance tests (ITT demonstrated that exenatide decreased the ability of the mice to tolerate insulin compared with placebo. The AUC of ITT in the exenatide group were also significantly (P = 0.006 lower than in the placebo group. In conclusion, a single dose of exenatide was able to decrease glucose intolerance and

[The impacts of low-dose corticosteroids infusion given in different manners on refractory septic shock patients].

Science.gov (United States)

Chen, Zhi; Yang, Chunli; He, Huiwei; He, Zhaohui

2015-06-01

To discuss the influence of different ways of low-dose corticosteroids infusion on hemodynamics, changes in blood glucose level and prognosis in patients with refractory septic shock. A prospective single-blind randomized controlled trial was conducted. Refractory septic shock patients admitted to the Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from April 1st, 2013 to October 31st, 2014 were enrolled for the study. The patients were divided into control group and research group by random number table. Besides conventional treatment for septic shock, patients in control group were given 200 mg/d hydrocortisone intravenous infusion lasting for 2 hours, while those of research group were given 8.33 mg/h hydrocortisone per hour with an intravenous pump. Treatment lasted for 5 continuous days for both groups. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) and arterial blood lactic acid in both groups were observed at the time of enroldment and 6 hours, 24 hours, 48 hours, and 5 days after the treatment. With a dynamic blood glucose monitor, mean blood glucose (MBG) level, largest amplitude of glycemic excursions (LAGE), glucose variability (GV), and the ratio of hyperglycaemia time were recorded. The duration of shock, length of intensive care unit (ICU) stay, total length of hospital stay, and 28-day mortality of both groups were recorded. Seventy-nine septic shock patients were assigned to the treatment, with 41 in control group, and 38 in research group. Compared with control group, 6-hour MAP in research group was obviously lowered [mmHg (1 mmHg=0.133 kPa): 66.31±4.38 vs. 68.58±4.86, t=1.062, P=0.033], but there were no significant differences in HR, MAP, CVP, lactic acid clearance and norepinephrine (NE) utilization rates at other time points between two groups. No significant difference in MBG was found between research group and control group (mmol/L: 8.69±2.14 vs. 9.95±3.87, t=1

The History of Target-Controlled Infusion

NARCIS (Netherlands)

Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

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Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

2014-04-08

Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

Science.gov (United States)

Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

2014-01-01

Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

International Nuclear Information System (INIS)

Wong, K.L.; Tyce, G.M.

1983-01-01

The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

Science.gov (United States)

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

An experimental study on the influence of infusion speed on the early mechanism of embolic effect of arterially infused absolute Ethanol in the rat

International Nuclear Information System (INIS)

Han, Joon Koo; Kim, Woo Ho; Lee, Byung Hee; Park, Kil Sun; Park, Jae Hyung; Kim, Chu Wan; Han, Man Chung

1990-01-01

In order to clarify the early mechanism of action of the tissue necrosis induced by intraarterially infused absolute ethanol, abdominal aortography and histopathologic examination after absolute ethanol infusion into aorta at fast (0.4ml/sec) and slow speed (0.04ml/sec) were performed on 22 rats (2 controls, 7 in fast infusion group, 7 in slow infusion group, 3 in fast and 3 in slow infusion groups during aorta compression, respectively). Histopathologic features under the light and scanning electron microscope were correlated with the angiographic findings within 30 minutes after ethanol infusion. The results are as follows : 1. In fast infusion group, histopathologic examination of the kidney showed severe glomerular and tubular damage. Extensive damage on endothelial and medial layer was noted in arteries, and fresh thrombi originated from the damaged arterial wall were seen. 2. Angiographic findings in the fast infusion group were luminal irregularity and early obstruction of large arteries. And circulation time was prolonged. 3. In slow infusion group, histopathologic examination of the kidney showed focal area of severe glomerular and tubular damage on relatively normal background. Endothelial and muscular damage was noted in arteries, but the degree of the damage was less severe than that of the fast infusion group. 4. Angiographic findings in the slow infusion group were focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but obstruction of the major arteries was not seen

Infusing Systems Thinking into Career Counseling

Science.gov (United States)

Ryan, Charles W.; Tomlin, James H.

2010-01-01

This study examined the role of career counselors in infusing systems thinking into occupational advising. The authors conducted a qualitative review and analysis of selected literature on systems thinking and analyzed trends for adaptation to career counseling practice. This analysis suggests that career counselors need to infuse systems…

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

DEFF Research Database (Denmark)

Storgaard, H; Song, X M; Jensen, C B

2001-01-01

before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide......To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P

Is continuous infusion of imipenem always the best choice?

Science.gov (United States)

Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.