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Sample records for insulin order form

  1. Ordered biological nanostructures formed from chaperonin polypeptides

    Science.gov (United States)

    Trent, Jonathan D. (Inventor); McMillan, R. Andrew (Inventor); Kagawa, Hiromi (Inventor); Paavola, Chad D. (Inventor)

    2010-01-01

    The following application relates to nanotemplates, nanostructures, nanoarrays and nanodevices formed from wild-type and mutated chaperonin polypeptides, methods of producing such compositions, methods of using such compositions and particular chaperonin polypeptides that can be utilized in producing such compositions.

  2. Quaternion orders, quadratic forms, and Shimura curves

    CERN Document Server

    Alsina, Montserrat

    2004-01-01

    Shimura curves are a far-reaching generalization of the classical modular curves. They lie at the crossroads of many areas, including complex analysis, hyperbolic geometry, algebraic geometry, algebra, and arithmetic. The text provides an introduction to the subject from a theoretic and algorithmic perspective. The main topics covered in it are Shimura curves defined over the rational number field, the construction of their fundamental domains, and the determination of their complex multiplication points. The study of complex multiplication points in Shimura curves leads to the study of families of binary quadratic forms with algebraic coefficients and to their classification by arithmetic Fuchsian groups. In this regard, the authors develop a theory full of new possibilities which parallels Gauss' theory on the classification of binary quadratic forms with integral coefficients by the action of the modular group. Each topic covered in the book begins with a theoretical discussion followed by carefully worked...

  3. Functional labeling of insulin receptor subunits in live cells. Alpha 2 beta 2 species is the major autophosphorylated form

    International Nuclear Information System (INIS)

    Le Marchand-Brustel, Y.; Ballotti, R.; Gremeaux, T.; Tanti, J.F.; Brandenburg, D.; Van Obberghen, E.

    1989-01-01

    Both receptor subunits were functionally labeled in order to provide methods allowing, in live cells and in broken cell systems, concomitant evaluation of the insulin receptor dual function, hormone binding, and kinase activity. In cell-free systems, insulin receptors were labeled on their alpha-subunit with 125I-photoreactive insulin, and on their beta-subunit by autophosphorylation. Thereafter, phosphorylated receptors were separated from the complete set of receptors by means of anti-phosphotyrosine antibodies. Using this approach, a subpopulation of receptors was found which had bound insulin, but which were not phosphorylated. Under nonreducing conditions, receptors appeared in three oligomeric species identified as alpha 2 beta 2, alpha 2 beta, and alpha 2. Mainly the alpha 2 beta 2 receptor species was found to be phosphorylated while insulin was bound to alpha 2 beta 2, alpha 2 beta, and alpha 2 forms. In live cells, biosynthetic labeling of insulin receptors was used. Receptors were first labeled with [35S]methionine. Subsequently, the addition of insulin led to receptor autophosphorylation by virtue of the endogenous ATP pool. The total amount of [35S]methionine-labeled receptors was precipitated with antireceptor antibodies, whereas with anti-phosphotyrosine antibodies, only the phosphorylated receptors were isolated. Using this approach we made the two following key findings: (1) Both receptor species, alpha 2 beta 2 and alpha 2 beta, are present in live cells and in comparable amounts. This indicates that the alpha 2 beta form is not a degradation product of the alpha 2 beta 2 form artificially generated during receptor preparation. (2) The alpha 2 beta 2 species is the prevalently autophosphorylated form

  4. Insulin

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  5. Using standardized insulin orders to improve patient safety in a tertiary care centre.

    Science.gov (United States)

    Doyle, Mary-Anne; Brez, Sharon; Sicoli, Silvana; De Sousa, Filomena; Keely, Erin; Malcom, Janine C

    2014-04-01

    To standardize insulin prescribing practices for inpatients, improve management of hypoglycemia, reduce reliance on sliding scales, increase use of basal-bolus insulin and improve patient safety. Patients with diabetes were admitted to 2 pilot inpatient units followed by corporate spread to all insulin-treated patients on noncritical care units in a Canadian tertiary care multicampus teaching hospital. Standardized preprinted insulin and hypoglycemia management orders, decision support tools and multidisciplinary education strategies were developed, tested and implemented by way of the Model for Improvement and The Ottawa Model for Research Process. Clinical and balance measures were evaluated through statistical process control. Patient safety was improved through a reduction in hypoglycemia and decreased dependence on correctional scales. Utilization of the preprinted orders approached the target of 70% at the end of the test period and was sustained at 89% corporately 3 years post-implementation. The implementation of a standardized, preprinted insulin order set facilitates best practices for insulin therapy, improves patient safety and is highly supported by treating practitioners. The utilization of formal quality-improvement methodology promoted efficiency, enhanced sustainability, increased support among clinicians and senior administrators, and was effective in instituting sustained practice change in a complex care centre. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  6. An Algorithm for Higher Order Hopf Normal Forms

    Directory of Open Access Journals (Sweden)

    A.Y.T. Leung

    1995-01-01

    Full Text Available Normal form theory is important for studying the qualitative behavior of nonlinear oscillators. In some cases, higher order normal forms are required to understand the dynamic behavior near an equilibrium or a periodic orbit. However, the computation of high-order normal forms is usually quite complicated. This article provides an explicit formula for the normalization of nonlinear differential equations. The higher order normal form is given explicitly. Illustrative examples include a cubic system, a quadratic system and a Duffing–Van der Pol system. We use exact arithmetic and find that the undamped Duffing equation can be represented by an exact polynomial differential amplitude equation in a finite number of terms.

  7. Perturbative calculations with the first order form of gauge theories

    Science.gov (United States)

    Brandt, F. T.; McKeon, D. G. C.

    2015-05-01

    The first- and second-order forms of gauge theories are classically equivalent; we consider the consequence of quantizing the first-order form using the Faddeev-Popov approach. Both the Yang-Mills and the Einstein-Hilbert actions are considered. An advantage of this approach is that the interaction vertices are quite simple, being independent of momenta. However, it is necessary to consider the propagator for two fields (including a mixed propagator). We derive the Feynman rules for both models and consider the one-loop correction for the thermal energy momentum tensor.

  8. Glass-forming liquids: one or more "order" parameters"

    DEFF Research Database (Denmark)

    Bailey, Nicholas; Christensen, Tage Emil; Jakobsen, Bo

    2008-01-01

    as a few exceptions, are briefly presented. Finally, we briefly discuss a new conjecture according to which experiments at varying temperature and pressure follow the density scaling expression for the relaxation time, τ = F(ρ^x/T ) (ρ and T are density and temperature), if and only if the liquid......We first summarize the classical arguments that the vast majority of glass-forming liquids require more than one ‘order' parameter for their description. Critiques against this conventional wisdom are then presented, and it is argued that the matter deserves to be reconsidered in the light...... that a description with a single "order" parameter applies to a good approximation whenever thermal equilibrium fluctuations of fundamental variables like energy and pressure are strongly correlated. Results from computer simulations showing that this is the case for a number of simple glass-forming liquids, as well...

  9. 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

  10. A Test of Macromolecular Crystallization in Microgravity: Large, Well-Ordered Insulin Crystals

    Science.gov (United States)

    Borgstahl, Gloria E. O.; Vahedi-Faridi, Ardeschir; Lovelace, Jeff; Bellamy, Henry D.; Snell, Edward H.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Crystals of insulin grown in microgravity on space shuttle mission STS-95 were extremely well-ordered and unusually large (many > 2 mm). The physical characteristics of six microgravity and six earth-grown crystals were examined by X-ray analysis employing superfine f slicing and unfocused synchrotron radiation. This experimental setup allowed hundreds of reflections to be precisely examined for each crystal in a short period of time. The microgravity crystals were on average 34 times larger, had 7 times lower mosaicity, had 54 times higher reflection peak heights and diffracted to significantly higher resolution than their earth grown counterparts. A single mosaic domain model could account for reflections in microgravity crystals whereas reflections from earth crystals required a model with multiple mosaic domains. This statistically significant and unbiased characterization indicates that the microgravity environment was useful for the improvement of crystal growth and resultant diffraction quality in insulin crystals and may be similarly useful for macromolecular crystals in general.

  11. Second order statistics of bilinear forms of robust scatter estimators

    KAUST Repository

    Kammoun, Abla

    2015-08-12

    This paper lies in the lineage of recent works studying the asymptotic behaviour of robust-scatter estimators in the case where the number of observations and the dimension of the population covariance matrix grow at infinity with the same pace. In particular, we analyze the fluctuations of bilinear forms of the robust shrinkage estimator of covariance matrix. We show that this result can be leveraged in order to improve the design of robust detection methods. As an example, we provide an improved generalized likelihood ratio based detector which combines robustness to impulsive observations and optimality across the shrinkage parameter, the optimality being considered for the false alarm regulation.

  12. Insulin enhances the peroxidase activity of heme by forming heme-insulin complex: Relevance to type 2 diabetes mellitus.

    Science.gov (United States)

    Huang, Yi; Yang, Zhen; Xu, Huan; Zhang, Pengfei; Gao, Zhonghong; Li, Hailing

    2017-09-01

    Evidences have implicated the involvement of heme in the type 2 diabetes mellitus (T2Dm) pathogenesis, but possible mediators linking between heme and diabetes are still poorly understood. Here, we explored a potential mechanism that linked heme, insulin and diabetes. Our results demonstrated the formation of heme-insulin complex by two classical methods, i.e. UV-vis and capillary electrophoresis-frontal analysis (CE-FA). UV-vis results implied heme binding insulin via bis-histidine sites, and CE-FA further revealed that, when insulin uses two sites binding with heme, this interaction occurs at high affinity (K d =3.13×10 -6 M). Molecule docking supported that histidine-B5 of insulin binds with heme-Fe. In addition to that, tyrosine-B26, phenylalanine-B1 and valine-B2 are also contributed to binding heme. The binding amplified the peroxidase activity of heme itself. Under oxidative and nitrative stress, it affects pathogenesis of diabetes from two aspects: promoting insulin cross-linking that leads to permanent loss of insulin functionality on one hand, and enhancing protein tyrosine nitration that may result in inactivation of proteins associated with diabetes on the other hand. This study suggested that the enhanced peroxidase activity of heme through binding with insulin might be a previously unrecognized contributor to the pathogenesis of T2Dm in some heme-associated disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Insulin Therapy

    Science.gov (United States)

    ... Your Health Resources Drugs, Procedures & Devices Prescription Medicines Insulin Therapy Insulin Therapy Share Print When you digest food, your ... you eat into glucose (a form of sugar). Insulin allows this glucose to enter all the cells ...

  14. Isolation of complexes formed between insulin-like growth factor-binding protein-3 and transferrin from the human serum

    Directory of Open Access Journals (Sweden)

    Miljuš Goran

    2012-01-01

    Full Text Available Insulin-like growth factors (IGFs play an important role in the regulation of cell growth, differentiation and metabolism. The amount of free, biologically active IGFs is regulated by the IGF-binding proteins (IGFBPs. IGFBP-3 is the most abundant binding protein and it is known to interact with other circulating proteins, including transferrin (Tf. In order to elucidate the possible role of IGF/IGFBP-3 in the iron metabolism, it is necessary to isolate IGFBP-3/Tf complexes. Several affinity-based techniques were employed. Results have shown that only double immunoprecipitation method with anti-Tf and anti-IGFBP-3 antibodies selectively separated complexes from other molecular forms, such as monomers, oligomers or fragments of IGFBP-3 and Tf. Isolated complexes can now be used to investigate the relationship between IGF/IGFBP-3 and iron, both in structural and metabolic tеrms.

  15. Single-order-parameter description of glass-forming liquids

    DEFF Research Database (Denmark)

    Ellegaard, Niels Langager; Christensen, Tage Emil; Christiansen, Peder Voetmann

    2007-01-01

    Thermoviscoelastic linear-response functions are calculated from the master equation describing viscous liquid inherent dynamics. From the imaginary parts of the frequency-dependent isobaric specific heat, isothermal compressibility, and isobaric thermal expansion coefficient, we define a "linear...... dynamic Prigogine-Defay ratio" with the property that if this ratio is unity at one frequency, then it is unity at all frequencies. This happens if and only if there is a single-order-parameter description of the thermoviscoelastic linear responses via an order parameter which may be nonexponential...

  16. Forming Circle Formations of Anonymous Mobile Agents With Order Preservation

    NARCIS (Netherlands)

    Wang, Chen; Xie, Guangming; Cao, Ming

    2013-01-01

    We propose distributed control laws for a group of anonymous mobile agents to form desired circle formations when the agents move in the one-dimensional space of a circle. The agents are modeled by kinematic points. They share the common knowledge of the orientation of the circle, but are oblivious

  17. Colour picking: the pecking order of form and function

    NARCIS (Netherlands)

    F.-M. Nack (Frank); A.S.K. Manniesing; L. Hardman (Lynda)

    2003-01-01

    textabstractMultimedia presentation generation has to be able to balance the functional aspects of a presentation that address the information needs of the user, and its aesthetic form. We demonstrate our approach using automatic colour design for which we integrate relevant aspects of colour

  18. The cephalic phase insulin response to nutritive and low-calorie sweeteners in solid and beverage form.

    Science.gov (United States)

    Dhillon, Jaapna; Lee, Janice Y; Mattes, Richard D

    2017-11-01

    The purpose of the study was to examine the role of the cephalic phase insulin response (CPIR) following exposure to nutritive and low-calorie sweeteners in solid and beverage form in overweight and obese adults. In addition, the role of learning on the CPIR to nutritive and low-calorie sweetener exposure was tested. Sixty-four overweight and obese adults (age: 18-50years, BMI: 24-37kg/m 2 , body fat percentage>25% for men and >32% for women) were sham-fed (at 2-minute intervals for 14min) a randomly assigned test load comprised of a nutritive (sucrose) or low-calorie sweetener (sucralose) in beverage or solid form in phase 1 of the study. A 2-3ml blood sample was collected before and 2, 6, 10, 14, 61, 91 and 121min after oral exposure for serum insulin and glucose analysis. During phase 2, participants underwent a 2-week training period to facilitate associative learning between the sensory properties of test loads and their post-ingestive effects. In phase 3, participants were retested for their cephalic phase responses as in phase 1. Participants were classified as responders if they demonstrated a positive insulin response (rise of serum insulin above baseline i.e. Δ insulin) 2min post-stimulus in phase 1. Among responders exposed to the same sweetener in Phases 1 and 3, the proportion of participants that displayed a rise of insulin with oral exposure to sucralose was significantly greater when the stimulus was in the solid form compared to the beverage form. Sucralose and sucrose exposure elicited similarly significant increases in serum insulin 2min after exposure and significant decreases after 2min in responders in both food forms. The solid food form elicited greater CPIR over 2, 6 and 10min than the beverage form. There was no effect of learning on insulin responses after training. The results indicate the presence of a significant CPIR in a subset of individuals with overweight or obesity after oral exposure to sucralose, especially when present in

  19. insulin

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... camel gene's structure and function were confirmed and found to be 86.36 and 87.5% similar in form and product, respectively, to that of human proinsulin. The C chain has. 27/35 identical amino acids (77.14%) and 8 of the amino acids are conserved changes. The camel proinsulin gene has similar three ...

  20. High-order upwind schemes for the wave equation on overlapping grids: Maxwell's equations in second-order form

    Science.gov (United States)

    Angel, Jordan B.; Banks, Jeffrey W.; Henshaw, William D.

    2018-01-01

    High-order accurate upwind approximations for the wave equation in second-order form on overlapping grids are developed. Although upwind schemes are well established for first-order hyperbolic systems, it was only recently shown by Banks and Henshaw [1] how upwinding could be incorporated into the second-order form of the wave equation. This new upwind approach is extended here to solve the time-domain Maxwell's equations in second-order form; schemes of arbitrary order of accuracy are formulated for general curvilinear grids. Taylor time-stepping is used to develop single-step space-time schemes, and the upwind dissipation is incorporated by embedding the exact solution of a local Riemann problem into the discretization. Second-order and fourth-order accurate schemes are implemented for problems in two and three space dimensions, and overlapping grids are used to treat complex geometry and problems with multiple materials. Stability analysis of the upwind-scheme on overlapping grids is performed using normal mode theory. The stability analysis and computations confirm that the upwind scheme remains stable on overlapping grids, including the difficult case of thin boundary grids when the traditional non-dissipative scheme becomes unstable. The accuracy properties of the scheme are carefully evaluated on a series of classical scattering problems for both perfect conductors and dielectric materials in two and three space dimensions. The upwind scheme is shown to be robust and provide high-order accuracy.

  1. [Glycemic index and insulin response to the ingestion of precooked corn flour in the form of "arepa" in healthy individuals].

    Science.gov (United States)

    Semprún-Fereira, M; Ryder, E; Morales, L M; Gómez, M E; Raleigh, X

    1994-09-01

    With the purpose of exploring the glucose and insulin responses to a breakfast composed of a complex carbohydrate (CC) in the form of a "arepa" prepared with precooked corn flour, with or without the addition of protein and fat (CC + P + F), we studied 6 healthy volunteers, ages ranging from 26-50 years and body mass index of 24.5 +/- 1.32. Three tests were performed on each individual: 1) 75 g OGTT, 2) Ingestion of 75 g of CC ("arepa") and 3) Ingestion of 75 g of CC + 6.7 g protein (low fat cheese) and 4 g fat (margarine). Glycemic values (glucose - oxidase method) and insulinemia (radioimmunoassay) were determined at basal, 30, 60, 120, 180 and 240 min. Glucose (GA) and insulin (IA) areas, glycemic index (GI) and insulin/glucose ratio (I/G) were calculated. We found that the "arepa" has a high GI (71.5%) that it is increased, although not significatively to 140% with the addition of protein and fat. Total GA as well as IA obtained for CC and for CC + P + F were similar to OGTT, however the profiles of the glucose and insulin responses during CC and CC + P + F were less abrupt but more prolonged, resulting in a greater I/G ratio for OGTT in comparison with CC or CC + P + F during the initial steps. We conclude that GI of this corn bread ("arepa") is high in comparison to other complex carbohydrates and it is not altered by the addition of protein and fat. This is possibly due to glucose and insulin responses similar to that produced by OGTT.

  2. Higher-Order Beta Matching with Solutions in Long Beta-Eta Normal Form

    DEFF Research Database (Denmark)

    Støvring, Kristian

    2006-01-01

    Higher-order matching is a special case of unification of simply-typed lambda-terms: in a matching equation, one of the two sides contains no unification variables. Loader has recently shown that higher-order matching up to beta equivalence is undecidable, but decidability of higher-order matching...... up to beta-eta equivalence is a long-standing open problem.We show that higher-order matching up to beta-eta equivalence is decidable if and only if a restricted form of higher-order matching up to beta equivalence is decidable: the restriction is that solutions must be in long beta-eta normal form....

  3. A Validated RP-HPLC Method for the Determination of Recombinant Human Insulin in Bulk and Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    B. A. Moussa

    2010-01-01

    Full Text Available A modified RP-HPLC method was developed for the quantitative determination of recombinant human insulin in bulk and pharmaceutical dosage form with reduced retention time. Study of the effects of the column temperature, pH of the mobile phase and presence of vial additives (phenol and m-cresol, or impurities (A-21 Disamido on the accuracy of the assay were assessed. Separation was achieved using a Hypersil BDS C-18 column and the mobile phase was composed of solution A (aqueous solution of 28.3 anhydrous Na2SO4g/L, pH 2.3 and solution B (28.5 g anhydrous Na2SO4 g/L in 50:50 mixture of water and acetonitrile, pH 2.3 in a ratio 48:52 (v/v at 45–50 °C. The column temperature was 40 °C, the flow rate was 1 mL/min and detection was performed at 216 nm. The procedures were validated according to international conference on harmonization (ICH guidelines. Recovery study was done applying standard addition technique for further validation of the procedure. The retention time of recombinant human insulin was 19.7 min as compared to 29 min obtained by the reference method. Analytical conditions fluctuations or presence of vial additives or impurities did not show any significant effect on the accuracy of the method. The prepared standard insulin solution in 0.01 N HCl was found to be stable for 5 days. Statistical comparison showed no significant difference between the described method and reference method regarding the accuracy and precision. The modified method can be applied for routine quality control applications for determination of recombinant human insulin.

  4. The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the old order of Amish.

    Science.gov (United States)

    Mentuccia, Daniela; Thomas, Matthew J; Coppotelli, Giuseppe; Reinhart, Laurie J; Mitchell, Braxton D; Shuldiner, Alan R; Celi, Francesco S

    2005-11-01

    A common polymorphism of the type 2 deiodinase gene (Thr92Ala DIO2) was found to be associated with insulin resistance in a mixed Caucasian population. The aim of this study was to investigate the association of the Thr92Ala DIO2 variant to indices of insulin resistance in the Old Order Amish. A genotype-phenotype association study was performed at the research clinic in Strasburg, Pennsylvania, and the molecular genetics laboratory at the University of Maryland, Baltimore, Maryland, and the National Institutes of Health, Bethesda, Maryland. A total of 1,268 subjects participated in the Amish Family Diabetes Study. An association among the Thr92Ala DIO2 variant and type 2 diabetes, indices of insulin resistance (HOMA-IR), insulin secretion, free thyroid hormones, and thyrotropin (TSH) was found. No association was found among the Thr92Ala DIO2 variant and type 2 diabetes, impaired glucose tolerance, or body mass index (BMI) in the Amish. In nondiabetics (n = 747), the Ala92 allele tended to be associated with decreased rather then increased insulin secretion. No differences were observed in thyroid hormones or TSH. Contrary to prior findings, the Thr92Ala DIO2 variant tends to be associated with increased rather then decreased insulin sensitivity in the Amish. These findings could be secondary to a different genetic background or to environmental factors specific for this population.

  5. Reliability Estimation of the Pultrusion Process Using the First-Order Reliability Method (FORM)

    NARCIS (Netherlands)

    Baran, Ismet; Tutum, Cem C.; Hattel, Jesper H.

    2013-01-01

    In the present study the reliability estimation of the pultrusion process of a flat plate is analyzed by using the first order reliability method (FORM). The implementation of the numerical process model is validated by comparing the deterministic temperature and cure degree profiles with

  6. Reliability Estimation of the Pultrusion Process Using the First-Order Reliability Method (FORM)

    DEFF Research Database (Denmark)

    Baran, Ismet; Tutum, Cem Celal; Hattel, Jesper Henri

    2013-01-01

    In the present study the reliability estimation of the pultrusion process of a flat plate is analyzed by using the first order reliability method (FORM). The implementation of the numerical process model is validated by comparing the deterministic temperature and cure degree profiles...... with corresponding analyses in the literature. The centerline degree of cure at the exit (CDOCE) being less than a critical value and the maximum composite temperature (Tmax) during the process being greater than a critical temperature are selected as the limit state functions (LSFs) for the FORM. The cumulative...... distribution functions of the CDOCE and Tmax as well as the correlation coefficients are obtained by using the FORM and the results are compared with corresponding Monte-Carlo simulations (MCS). According to the results obtained from the FORM, an increase in the pulling speed yields an increase...

  7. Long and short range order structural analysis of In-situ formed biphasic calcium phosphates.

    Science.gov (United States)

    Kim, Dong-Hyun; Hwang, Kyu-Hong; Lee, Ju Dong; Park, Hong-Chae; Yoon, Seog-Young

    2015-01-01

    Biphasic calcium phosphates (BCP) have attracted considerable attention as a bone graft substitute. In this study, BCP were prepared by aqueous co-precipitation and calcination method. The crystal phases of in-situ formed BCP consisting of hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) were controlled by the degree of calcium deficiency of precursors. The long and short range order structures of biphasic mixtures was investigated using Rietveld refinement technique and high resolution Raman spectroscopy. The refined structural parameters of in-situ formed BCP confirmed that all the investigated structures have crystallized in the corresponding hexagonal (space group P63/m) and rhombohedral (space group R3c) structures. The crystal phases, Ca/P molar ratio, and lattice parameters of in-situ formed BCP consisting of HAp and β-TCP were controlled by the degree of calcium deficiency of calcium phosphate precursors. The significant short range order structural change of BCP was determined by Raman analysis. The long and short range order structural changes of in-situ formed BCP might be due to the coexistence of β-TCP and HAp crystal phases.

  8. First-order systems of linear partial differential equations: normal forms, canonical systems, transform methods

    Directory of Open Access Journals (Sweden)

    Heinz Toparkus

    2014-04-01

    Full Text Available In this paper we consider first-order systems with constant coefficients for two real-valued functions of two real variables. This is both a problem in itself, as well as an alternative view of the classical linear partial differential equations of second order with constant coefficients. The classification of the systems is done using elementary methods of linear algebra. Each type presents its special canonical form in the associated characteristic coordinate system. Then you can formulate initial value problems in appropriate basic areas, and you can try to achieve a solution of these problems by means of transform methods.

  9. Cross-Cultural Adaptation of the Physician Orders for Life-Sustaining Treatment Form to Brazil.

    Science.gov (United States)

    Mayoral, Vania F S; Fukushima, Fernanda B; Rodrigues, Aniela M; Carvalho, Raissa P; Carvalho, Larissa P; Pinheiro, Leandro A F V; Polegato, Bertha F; Minicucci, Marcos F; Bassett, Rick; Moss, Alvin H; Steinberg, Karl E; Vidal, Edison I O

    2018-02-12

    The Physician Orders for Life-Sustaining Treatment (POLST) paradigm is considered one of the most important strategies to respect patients' values at the end of life in the United States. The cross-cultural adaptation of POLST entailed several methodological considerations, which may be informative for international researchers who may also consider bringing POLST to their countries as a means to promote care at the end of life that is consistent with patients' preferences. To report the methods and outcome of the cross-cultural adaptation of the POLST form to Brazil. Cross-cultural adaptation study. Twenty physicians and 10 patients at a university hospital participated in the pilot tests. The cross-cultural adaptation process included choosing which existing POLST form(s) to use as a source, deciding the intended reading level, which healthcare professionals should be allowed to sign the form, and consultation with attorneys, bioethicists, and members of the National POLST Paradigm Task Force. Pilot tests occurred in two stages using different approaches. First, 20 physicians were trained about POLST and asked for any unclear aspects related to the form. Second, trained investigators completed POLST forms after engaging in advance care planning conversations with 10 hospitalized patients or patients' surrogates. This report provides a basis for future cross-cultural adaptations of POLST to other countries. The authors hope such new adaptations will broaden the possibilities of research using POLST and also may promote wider provision of care at the end of life that is consistent with patients' preferences.

  10. Sharper focal spot formed by higher-order radially polarized laser beams.

    Science.gov (United States)

    Kozawa, Yuichi; Sato, Shunichi

    2007-06-01

    The intensity distributions near the focal point for radially polarized laser beams including higher-order transverse modes are calculated based on vector diffraction theory. For higher-order radially polarized mode beams as well as a fundamental mode (R-TEM01*) beam, the strong longitudinal component forms a sharper spot at the focal point under a high-NA focusing condition. In particular, double-ring-shaped radially polarized mode (R-TEM11*) beams can effectively reduce the focal spot size because of destructive interference between the inner and the outer rings with pi phase shift. Compared with an R-TEM01* beam focusing in a limit of NA=1, the full width at half-maximum values of the focal spot for an R-TEM11* beam are decreased by 13.6% for the longitudinal component and 25.8% for the total intensity.

  11. A simple design rule for 1st order form-closure of underactuated hands

    Directory of Open Access Journals (Sweden)

    S. Krut

    2011-02-01

    Full Text Available The property of form-closure of a grasp, as generally defined in the literature, is based on the assumption that contact points between the hand and the object are fixed in space. However, this assumption is false when considering a grasp exerted by an underactuated hand, since in this case, it is not possible to control the position of each phalanx independently. In spite of researchers' interest in studying form-closure, none of the available published work on this subject takes into consideration the particular kinematics of underactuated hands. Actually, there are few available tools to qualify or quantify the stability of a grasp exerted by an underactuated hand, thus the design of underactuated hands mostly results from an intuitive approach. This paper aims to reduce this gap.

    A classification of underactuated hands is proposed, based on the expression of contact forces. This highlights the influence of non-backdrivable mechanisms introduced in the transmission of the closing motion of the hand on the stability of the grasp. The way to extend the original definition of form-closure to underactuated grasps is illustrated. A more general definition is formulated, which checks the stability of the set "object + hand". Using this new definition, a simple rule is proposed for designing a hand capable of achieving 1st order form-closed grasps.

    This paper was presented at the IFToMM/ASME International Workshop on Underactuated Grasping (UG2010, 19 August 2010, Montréal, Canada.

  12. Optimization of accelerator parameters using normal form methods on high-order transfer maps

    Energy Technology Data Exchange (ETDEWEB)

    Snopok, Pavel [Michigan State Univ., East Lansing, MI (United States)

    2007-05-01

    Methods of analysis of the dynamics of ensembles of charged particles in collider rings are developed. The following problems are posed and solved using normal form transformations and other methods of perturbative nonlinear dynamics: (1) Optimization of the Tevatron dynamics: (a) Skew quadrupole correction of the dynamics of particles in the Tevatron in the presence of the systematic skew quadrupole errors in dipoles; (b) Calculation of the nonlinear tune shift with amplitude based on the results of measurements and the linear lattice information; (2) Optimization of the Muon Collider storage ring: (a) Computation and optimization of the dynamic aperture of the Muon Collider 50 x 50 GeV storage ring using higher order correctors; (b) 750 x 750 GeV Muon Collider storage ring lattice design matching the Tevatron footprint. The normal form coordinates have a very important advantage over the particle optical coordinates: if the transformation can be carried out successfully (general restrictions for that are not much stronger than the typical restrictions imposed on the behavior of the particles in the accelerator) then the motion in the new coordinates has a very clean representation allowing to extract more information about the dynamics of particles, and they are very convenient for the purposes of visualization. All the problem formulations include the derivation of the objective functions, which are later used in the optimization process using various optimization algorithms. Algorithms used to solve the problems are specific to collider rings, and applicable to similar problems arising on other machines of the same type. The details of the long-term behavior of the systems are studied to ensure the their stability for the desired number of turns. The algorithm of the normal form transformation is of great value for such problems as it gives much extra information about the disturbing factors. In addition to the fact that the dynamics of particles is represented

  13. Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice.

    Directory of Open Access Journals (Sweden)

    Sudhanshu P Raikwar

    Full Text Available Type 1 diabetes (T1D is caused by autoimmune disease that leads to the destruction of pancreatic β-cells. Transplantation of cadaveric pancreatic organs or pancreatic islets can restore normal physiology. However, there is a chronic shortage of cadaveric organs, limiting the treatment of the majority of patients on the pancreas transplantation waiting list. Here, we hypothesized that human iPS cells can be directly differentiated into insulin producing cells (IPCs capable of secreting insulin. Using a series of pancreatic growth factors, we successfully generated iPS cells derived IPCs. Furthermore, to investigate the capability of these cells to secrete insulin in vivo, the differentiated cells were transplanted under the kidney capsules of diabetic immunodeficient mice. Serum glucose levels gradually declined to either normal or near normal levels over 150 days, suggesting that the IPCs were secreting insulin. In addition, using MRI, a 3D organoid appeared as a white patch on the transplanted kidneys but not on the control kidneys. These organoids showed neo-vascularization and stained positive for insulin and glucagon. All together, these data show that a pancreatic organ can be created in vivo providing evidence that iPS cells might be a novel option for the treatment of T1D.

  14. Beating Homogeneous Nucleation and Tuning Atomic Ordering in Glass-Forming Metals by Nanocalorimetry.

    Science.gov (United States)

    Zhao, Bingge; Yang, Bin; Abyzov, Alexander S; Schmelzer, Jürn W P; Rodríguez-Viejo, Javier; Zhai, Qijie; Schick, Christoph; Gao, Yulai

    2017-12-13

    In this paper, the amorphous Ce 68 Al 10 Cu 20 Co 2 (atom %) alloy was in situ prepared by nanocalorimetry. The high cooling and heating rates accessible with this technique facilitate the suppression of crystallization on cooling and the identification of homogeneous nucleation. Different from the generally accepted notion that metallic glasses form just by avoiding crystallization, the role of nucleation and growth in the crystallization behavior of amorphous alloys is specified, allowing an access to the ideal metallic glass free of nuclei. Local atomic configurations are fundamentally significant to unravel the glass forming ability (GFA) and phase transitions in metallic glasses. For this reason, isothermal annealing near T g from 0.001 s to 25,000 s following quenching becomes the strategy to tune local atomic configurations and facilitate an amorphous alloy, a mixed glassy-nanocrystalline state, and a crystalline sample successively. On the basis of the evolution of crystallization enthalpy and overall latent heat on reheating, we quantify the underlying mechanism for the isothermal nucleation and crystallization of amorphous alloys. With Johnson-Mehl-Avrami method, it is demonstrated that the coexistence of homogeneous and heterogeneous nucleation contributes to the isothermal crystallization of glass. Heterogeneous rather than homogeneous nucleation dominates the isothermal crystallization of the undercooled liquid. For the mixed glassy-nanocrystalline structure, an extraordinary kinetic stability of the residual glass is validated, which is ascribed to the denser packed interface between amorphous phase and ordered nanocrystals. Tailoring the amorphous structure by nanocalorimetry permits new insights into unraveling GFA and the mechanism that correlates local atomic configurations and phase transitions in metallic glasses.

  15. Crystallographic characterization of two novel crystal forms of human insulin induced by chaotropic agents and a shift in pH

    Directory of Open Access Journals (Sweden)

    Norrman Mathias

    2007-12-01

    Full Text Available Abstract Background Insulin is a therapeutic protein that is widely used for the treatment of diabetes. Its biological function was discovered more than 80 years ago and it has since then been characterized extensively. Crystallization of the insulin molecule has always been a key activity since the protein is often administered by subcutaneous injections of crystalline insulin formulations. Over the years, insulin has been crystallized and characterized in a number of crystal systems. Results Interestingly, we have now discovered two new crystal forms of human insulin. The crystals were obtained when the two chaotropic agents, urea and thiocyanate were present in the crystallization experiments, and their structures were determined by X-ray crystallography. The crystals belong to the orthorhombic and monoclinic crystal systems, with space groups C2221 and C2 respectively. The orthorhombic crystals were obtained at pH 6.5 and contained three insulin hexamers in R6 conformation in the asymmetric unit whilst the monoclinic C2 crystals were obtained at pH 7.0 and contained one R6 hexamer in the asymmetric unit. Common for the two new crystals is a hexamer-hexamer interaction that has not been found in any of the previous crystal forms of insulin. The contacts involve a tight glutamate-glutamate interaction with a distance of 2.3 Å between groups. The short distance suggests a low barrier hydrogen bond. In addition, two tyrosine-tyrosine interactions occupying a known phenol binding pocket contribute to the stabilization of the contacts. Within the crystals, distinct binding sites for urea were found, adding further to the discussion on the role of urea in protein denaturation. Conclusion The change in space group from C2221 to C2 was primarily caused by an increase in pH. The fewer number of hexamer-hexamer interactions comprising the short hydrogen bond in the C2 space group suggest that pH is the driving force. In addition, the distance between

  16. Modified Inverse First Order Reliability Method (I-FORM) for Predicting Extreme Sea States.

    Energy Technology Data Exchange (ETDEWEB)

    Eckert-Gallup, Aubrey Celia; Sallaberry, Cedric Jean-Marie; Dallman, Ann Renee; Neary, Vincent Sinclair

    2014-09-01

    Environmental contours describing extreme sea states are generated as the input for numerical or physical model simulation s as a part of the stand ard current practice for designing marine structure s to survive extreme sea states. Such environmental contours are characterized by combinations of significant wave height ( ) and energy period ( ) values calculated for a given recurrence interval using a set of data based on hindcast simulations or buoy observations over a sufficient period of record. The use of the inverse first - order reliability method (IFORM) i s standard design practice for generating environmental contours. In this paper, the traditional appli cation of the IFORM to generating environmental contours representing extreme sea states is described in detail and its merits and drawbacks are assessed. The application of additional methods for analyzing sea state data including the use of principal component analysis (PCA) to create an uncorrelated representation of the data under consideration is proposed. A reexamination of the components of the IFORM application to the problem at hand including the use of new distribution fitting techniques are shown to contribute to the development of more accurate a nd reasonable representations of extreme sea states for use in survivability analysis for marine struc tures. Keywords: In verse FORM, Principal Component Analysis , Environmental Contours, Extreme Sea State Characteri zation, Wave Energy Converters

  17. Insulin Secretagogues

    Science.gov (United States)

    ... the Spikes Is mealtime insulin right for you? Insulin Secretagogues September 2017 Download PDFs English Espanol Editors ... Additional Resources Affordable Insulin Project FDA What are insulin secretagogues? Insulin secretagogues are one type of medicine ...

  18. Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues

    Czech Academy of Sciences Publication Activity Database

    Jiráček, Jiří; Žáková, Lenka; Antolíková, Emília; Watson, C. J.; Turkenburg, J. P.; Dodson, G. G.; Brzozowski, A. M.

    2010-01-01

    Roč. 107, č. 5 (2010), s. 1966-1970 ISSN 0027-8424 R&D Projects: GA MŠk(CZ) LC06077; GA AV ČR KJB400550702 Institutional research plan: CEZ:AV0Z40550506 Keywords : insulin * analogue * conformation * beta-turn * N-methylation Subject RIV: CC - Organic Chemistry Impact factor: 9.771, year: 2010

  19. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  20. A comparison of second order derivative based models for time domain reflectometry wave form analysis

    Science.gov (United States)

    Adaptive waveform interpretation with Gaussian filtering (AWIGF) and second order bounded mean oscillation operator Z square 2(u,t,r) are TDR analysis methods based on second order differentiation. AWIGF was originally designed for relatively long probe (greater than 150 mm) TDR waveforms, while Z s...

  1. Stability of linear systems in second-order form based on structure preserving similarity transformations

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Pommer, Christian; Kliem, Wolfhard

    2015-01-01

    of the transformation parameters into a new system (I, B 1, C 1) with a symmetrizable matrix C 1. This procedure facilitates stability investigations. We also consider systems with a Hamiltonian spectrum which discloses marginal stability after a Jordan form preserving transformation.......This paper deals with two stability aspects of linear systems of the form Ix¨+Bx˙+Cx=0 given by the triple (I, B, C). A general transformation scheme is given for a structure and Jordan form preserving transformation of the triple. We investigate how a system can be transformed by suitable choices...

  2. Dietary amino acids fed in free form and as protein components do not differently affect postprandial plasma insulin, glucagon, growth hormone and corticosterone responses in rats.

    Science.gov (United States)

    Nolles, J A; Van Straten, E M E; Bremer, B I; Koopmanschap, R E; Verstegen, M W A; Schreurs, V V A M

    2006-08-01

    This study examined, whether the postprandial fate of dietary amino acids from different amino acid sources is regulated by the responses of insulin, glucagon, corticosterone and growth hormone (GH). Male Wistar rats were cannulated in the vena jugularis and assigned to dietary groups. The diets contained 21% casein or the same amino acids in free form. In the free amino acid diets, methionine level was varied between the groups. The feed was supplied in two distinct meals. In previous experiments it was established that oxidative amino acid losses of the free amino acid diets and protein diets were different. After 3 weeks on those diets, it appeared that the differences in postprandial oxidative losses had been diminished. GH was measured every 12 min, from 144 min before the start of the experimental meal over the following 144 min. Insulin and corticosterone were measured six times from the start of the meal until 270 min after the meal. No differences have been observed between the hormonal responses to both meals at day 5 and at day 26. In conclusion, it has been found that the differences in the oxidative losses between protein and free amino acid meals are not mediated by the combined action of the insulin, glucagon, corticosterone and GH. Postprandial catabolism of amino acids is most probably regulated by substrate induction.

  3. Masked form priming is moderated by the size of the letter-order-free orthographic neighbourhood.

    Science.gov (United States)

    Burt, Jennifer S; Duncum, Sophie

    2016-03-16

    University students made lexical decisions to targets preceded by masked primes. In Experiment 1, transposed-letter primes were used also in the sandwich priming paradigm, in which the target is briefly pre-presented prior to the prime. The priming effects in the masked paradigm, but not in the sandwich paradigm, were moderated by the density of the letter-order-free neighbourhood of the target. In Experiment 2, letter-order-free neighbour prime words produced a priming cost in masked priming. These results are consistent with the idea that sandwich priming attenuates letter-order-free neighbour competition in target identification. Unexpectedly, no priming cost was produced by conventional (letter-position-preserving) word neighbour primes. Order-free neighbours may produce facilitation of target processing less, and more variably, than conventional neighbours.

  4. Insulin Pumps

    Science.gov (United States)

    ... Size: A A A Listen En Español Insulin Pumps Insulin pumps are small computerized devices that deliver insulin in ... tissue and is taped in place. The insulin pump is not an artificial pancreas (because you still ...

  5. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  6. Hexagonally Ordered Arrays of α-Helical Bundles Formed from Peptide-Dendron Hybrids

    Energy Technology Data Exchange (ETDEWEB)

    Barkley, Deborah A. [Department; Rokhlenko, Yekaterina [Department; Marine, Jeannette E. [Department; David, Rachelle [Department; Sahoo, Dipankar [Department; Watson, Matthew D. [Department; Koga, Tadanori [Department; Department; Osuji, Chinedum O. [Department; Rudick, Jonathan G. [Department

    2017-10-24

    Combining monodisperse building blocks that have distinct folding properties serves as a modular strategy for controlling structural complexity in hierarchically organized materials. We combine an α-helical bundle-forming peptide with self-assembling dendrons to better control the arrangement of functional groups within cylindrical nanostructures. Site-specific grafting of dendrons to amino acid residues on the exterior of the α-helical bundle yields monodisperse macromolecules with programmable folding and self-assembly properties. The resulting hybrid biomaterials form thermotropic columnar hexagonal mesophases in which the peptides adopt an α-helical conformation. Bundling of the α-helical peptides accompanies self-assembly of the peptide-dendron hybrids into cylindrical nanostructures. The bundle stoichiometry in the mesophase agrees well with the size found in solution for α-helical bundles of peptides with a similar amino acid sequence.

  7. Cutting blade dentitions in squaliform sharks form by modification of inherited alternate tooth ordering patterns

    OpenAIRE

    Underwood, Charlie J.; Johanson, Z.; Smith, M.M.

    2016-01-01

    The squaliform sharks represent one of the most speciose shark clades. Many adult squaliforms have blade-like teeth, either on both jaws or restricted to the lower jaw, forming a continuous, serrated blade along the jaw margin. These teeth are replaced as a single unit and successor teeth lack the alternate arrangement present in other elasmobranchs. Micro-CT scans of embryos of squaliforms and a related outgroup (Pristiophoridae) revealed that the squaliform dentition pattern represents a hi...

  8. Second-order nonlinear optical properties of mexylaminotriazine-functionalized glass-forming azobenzene derivatives

    Science.gov (United States)

    Umezawa, Hirohito; Jackson, Matthew; Lebel, Olivier; Nunzi, Jean-Michel; Sabat, Ribal Georges

    2016-10-01

    The second-order nonlinear optical coefficients of thin films of mexylaminotriazine-functionalized azobenzene molecular glass derivatives were measured using second harmonic generation. The thin films were poled using a custom corona poling set-up and the second harmonic light from a pulsed 1064-nm laser was detected. Four out of the six tested compounds showed optical nonlinearity and a maximum coefficient of 75 pm/V was obtained. The time dependence of the nonlinear coefficients was studied under ambient light and under dark; the second harmonic generation intensity stayed constant for thiazole-containing derivatives while a significant decay was measured for the other compounds.

  9. Enhancement of high-order harmonics in a plasma waveguide formed in clustered Ar gas.

    Science.gov (United States)

    Geng, Xiaotao; Zhong, Shiyang; Chen, Guanglong; Ling, Weijun; He, Xinkui; Wei, Zhiyi; Kim, Dong Eon

    2018-02-05

    Generation of high-order harmonics (HHs) is intensified by using a plasma waveguide created by a laser in a clustered gas jet. The formation of a plasma waveguide and the guiding of a laser beam are also demonstrated. Compared to the case without a waveguide, harmonics were strengthened up to nine times, and blue-shifted. Numerical simulation by solving the time-dependent Schrödinger equation in strong field approximation agreed well with experimental results. This result reveals that the strengthening is the result of improved phase matching and that the blue shift is a result of change in fundamental laser frequency due to self-phase modulation (SPM).

  10. Cutting blade dentitions in squaliform sharks form by modification of inherited alternate tooth ordering patterns

    Science.gov (United States)

    Underwood, Charlie; Johanson, Zerina; Smith, Moya Meredith

    2016-11-01

    The squaliform sharks represent one of the most speciose shark clades. Many adult squaliforms have blade-like teeth, either on both jaws or restricted to the lower jaw, forming a continuous, serrated blade along the jaw margin. These teeth are replaced as a single unit and successor teeth lack the alternate arrangement present in other elasmobranchs. Micro-CT scans of embryos of squaliforms and a related outgroup (Pristiophoridae) revealed that the squaliform dentition pattern represents a highly modified version of tooth replacement seen in other clades. Teeth of Squalus embryos are arranged in an alternate pattern, with successive tooth rows containing additional teeth added proximally. Asynchronous timing of tooth production along the jaw and tooth loss prior to birth cause teeth to align in oblique sets containing teeth from subsequent rows; these become parallel to the jaw margin during ontogeny, so that adult Squalus has functional tooth rows comprising obliquely stacked teeth of consecutive developmental rows. In more strongly heterodont squaliforms, initial embryonic lower teeth develop into the oblique functional sets seen in adult Squalus, with no requirement to form, and subsequently lose, teeth arranged in an initial alternate pattern.

  11. Presbycusis phenotypes form a heterogeneous continuum when ordered by degree and configuration of hearing loss.

    Science.gov (United States)

    Allen, Paul D; Eddins, David A

    2010-06-01

    Many reports have documented age-by-frequency increases in average auditory thresholds in various human populations. Despite this, the prevalence of different patterns of hearing loss in presbycusis remains uncertain. We examined 'presbycusis phenotypes' in a database of 960 subjects (552 female, 408 male, 18-92 years) that each had 30 measures of peripheral hearing sensitivity: pure tone audiograms for left and right ears from 0.25 to 8 kHz and DPOAE for each ear with F(mean)=1-6.4 kHz. Surprisingly, the hearing phenotypes did not naturally separate into discrete classes of presbycusis. Principal component (PC) analysis revealed that two principal components account for 74% of the variance among the 30 measures of hearing. The two components represent the overall degree (PC1) and configuration of loss (Flat vs. Sloping; PC2) and the phenotypes form a continuum when plotted against them. A heuristic partitioning of this continuum produced classes of presbycusis that vary in their degree of Sloping or Flat hearing loss, suggesting that the previously reported sub-types of presbycusis arise from the categorical segregation of a continuous and heterogeneous distribution. Further, most phenotypes lie intermediate to the extremes of either Flat or Sloping loss, indicating that if audiometric configuration does predict presbycusis etiology, then a mixed origin is the most prevalent. Copyright 2010 Elsevier B.V. All rights reserved.

  12. Serial order in word form retrieval: New insights from the auditory picture-word interference task.

    Science.gov (United States)

    Wilshire, Carolyn; Singh, Sunita; Tattersall, Catherine

    2016-02-01

    One important theoretical question about word production concerns whether the phonemes of a word are retrieved in parallel or in sequential order. To address this question, Meyer and Schriefers (Journal of Experimental Psychology: Learning, Memory, and Cognition 17:1146-1160, 1991) used an auditory picture-word interference task and manipulated the position of the phonemes shared between a distractor word and a target picture. They found that begin-related distractors (e.g., boat-bone) facilitated naming times when they were presented within 150 ms before or after the picture, whereas end-related distractors (e.g., cone-bone) were effective only if presented within 150 ms after the picture. This suggested that the word's end phonemes were activated later than the beginning ones. However, it remained unclear whether these effects genuinely reflected facilitation at the level of phonological retrieval. In this study, we examined later distractor presentation onsets, so that the distractors had little opportunity to influence earlier, lexical selection processes. At the latest onset tested, end-related-but not begin-related-distractors significantly facilitated naming. We concluded that late-presented distractors do indeed influence phonological encoding, and that their asymmetric effects support a sequential model of phoneme retrieval.

  13. The electric dipole form factor of the nucleon in chiral perturbation theory to sub-leading order

    Energy Technology Data Exchange (ETDEWEB)

    Mereghetti, E., E-mail: emanuele@physics.arizona.ed [Department of Physics, University of Arizona, Tucson, AZ 85721 (United States); Vries, J. de [KVI, Theory Group, University of Groningen 9747 AA Groningen (Netherlands); Hockings, W.H. [Department of Mathematics and Natural Sciences, Blue Mountain College, Blue Mountain, MS 38610 (United States); Maekawa, C.M. [Instituto de Matematica, Estatistica e Fisica, Universidade Federal do Rio Grande, Campus Carreiros, PO Box 474, 96201-900 Rio Grande, RS (Brazil); Kolck, U. van [Department of Physics, University of Arizona, Tucson, AZ 85721 (United States)

    2011-01-24

    The electric dipole form factor (EDFF) of the nucleon stemming from the QCD {theta}-bar term and from the quark color-electric dipole moments is calculated in chiral perturbation theory to sub-leading order. This is the lowest order in which the isoscalar EDFF receives a calculable, non-analytic contribution from the pion cloud. In the case of the {theta}-bar term, the expected lower bound on the deuteron electric dipole moment is |d{sub d}|{>=}1.4.10{sup -4{theta}}-bar e fm. The momentum dependence of the isovector EDFF is proportional to a non-derivative time-reversal-violating pion-nucleon coupling, and the scale for momentum variation-appearing, in particular, in the radius of the form factor-is the pion mass.

  14. Multifunctional Composite Microcapsules for Oral Delivery of Insulin.

    Science.gov (United States)

    Sun, Shaoping; Liang, Na; Gong, Xianfeng; An, Weiwei; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

    2016-12-28

    In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide- co -glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of -29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery.

  15. Multifunctional Composite Microcapsules for Oral Delivery of Insulin

    Science.gov (United States)

    Sun, Shaoping; Liang, Na; Gong, Xianfeng; An, Weiwei; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

    2016-01-01

    In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery. PMID:28036045

  16. Rapid fabrication of an ordered nano-dot array by the combination of nano-plastic forming and annealing methods

    International Nuclear Information System (INIS)

    Yoshino, Masahiko; Ohsawa, Hiroki; Yamanaka, Akinori

    2011-01-01

    In this paper, a new fabrication method for an ordered nano-dot array is developed. Combination of coating, nano-plastic forming and annealing processes is studied to produce uniformly sized and ordered gold nano-dot array on a quartz glass substrate. The experimental results reveal that patterning of a groove grid on the gold-coated substrate with NPF is effective to obtain the ordered gold nano-dot array. In the proposed fabrication process, the size of the gold nano-dot can be controlled by adjusting the groove grid size. A minimum gold nano-dot array fabricated on a quartz-glass substrate was 93 nm in diameter and 100 nm in pitch. Furthermore, the mechanism of nano-dot array generation by the presented process is investigated. Using a theoretical model it is revealed that the proposed method is capable of fabrication of smaller nano-dots than 10 nm by controlling process conditions adequately.

  17. Adherence to a Standardized Order Form for Gastric Cancer in a Referral Chemotherapy Teaching Hospital, Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    Mitra Asgarian

    2017-09-01

    Full Text Available Background: Standardized forms for prescription and medication administration are one solution to reduce medication errors in the chemotherapy process. Gastric cancer is the most common cancer in Iran. In this study, we have attempted to design and validate a standard printed chemotherapy form and evaluate adherence by oncologists and nurses to this form. Methods: We performed this cross-sectional study in a Mashhad, Iran teaching hospital from August 2015 until January 2016. A clinical pharmacist designed the chemotherapy form that included various demographic and clinical parameters and approved chemotherapy regimens for gastric cancer. Clinical oncologists that worked in this center validated the form. We included all eligible patients. A pharmacy student identified adherence by the oncologists and nurses to this form and probable medication errors. Results are mean ± standard deviation or number (percentages for nominal variables. Data analysis was performed using the SPSS 16.0 statistical package. Results:We evaluated 54 patients and a total of 249 chemotherapy courses. In 146 (58.63% chemotherapy sessions, the administered regimens lacked compatibility with the standard form. Approximately 66% of recorded errors occurred in the prescription phase and the remainder during the administration phase. The most common errors included improper dose (61% and wrong infusion time (34%. We observed that 37 dose calculation errors occurred in 32 chemotherapy sessions. Conclusions: In general, adherence by oncologists and nurses with the developed form for chemotherapy treatment of gastric cancer was not acceptable. These findings indicated the necessity for a standardized order sheet to simplify the chemotherapy process for the clinicians, and reduce prescription and administration errors.

  18. Fourth-order derivative spectrophotometric method for simultaneous determination of pseudoephedrine and naproxen in pharmaceutical dosage forms

    Science.gov (United States)

    Souri, Effat; Mosafer, Amir; Tehrani, Maliheh Barazandeh

    2016-01-01

    Combination dosage forms of naproxen sodium and pseudoephedrine hydrochloride are used for symptomatic treatment of cold and sinus disorders. In this study, fourth-order derivative spectrophotometric method was used for simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride. The method was linear over the range of 2-28 μg/ml for pseudoephedrine hydrochloride and 4-200 μg/ml for naproxen sodium. The within-day and between-day coefficient of variation values were less than 5.8% and 2.5% for pseudoephedrine hydrochloride and naproxen sodium, respectively. The application of the proposed method for simultaneous determination of naproxen and pseudoephedrine in dosage forms was demonstrated without any special pretreatment. PMID:27168748

  19. Surface enhanced Raman scattering by organic and inorganic semiconductors formed on laterally ordered arrays of Au nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Milekhin, Alexander G., E-mail: milekhin@thermo.isp.nsc.ru [A.V. Rzhanov Institute of Semiconductor Physics, Lavrentiev av. 13, 630090, Novosibirsk (Russian Federation); Novosibirsk State University, Pirogov str. 2, 630090, Novosibirsk (Russian Federation); Yeryukov, Nikolay A., E-mail: yeryukov@isp.nsc.ru [A.V. Rzhanov Institute of Semiconductor Physics, Lavrentiev av. 13, 630090, Novosibirsk (Russian Federation); Sveshnikova, Larisa L.; Duda, Tatyana A.; Rodyakina, Ekaterina E. [A.V. Rzhanov Institute of Semiconductor Physics, Lavrentiev av. 13, 630090, Novosibirsk (Russian Federation); Sheremet, Evgeniya S.; Ludemann, Michael; Gordan, Ovidiu D. [Semiconductor Physics, Chemnitz University of Technology, D-09107, Chemnitz (Germany); Latyshev, Alexander V. [A.V. Rzhanov Institute of Semiconductor Physics, Lavrentiev av. 13, 630090, Novosibirsk (Russian Federation); Novosibirsk State University, Pirogov str. 2, 630090, Novosibirsk (Russian Federation); Zahn, Dietrich R.T. [Semiconductor Physics, Chemnitz University of Technology, D-09107, Chemnitz (Germany)

    2013-09-30

    This work is devoted to the investigation of surface-enhanced Raman scattering by vibrational modes of cobalt phthalocyanine ultrathin films and CuS nanocrystals prepared using by organic molecular beam vapor deposition and the Langmuir–Blodgett technique, respectively, on laterally ordered arrays of Au nanoclusters formed by electron beam lithography on Si and GaAs substrates. The surface-enhanced Raman scattering study of cobalt phthalocyanine films demonstrates the strong dependence of Raman intensity of vibrational modes in cobalt phthalocyanine on the laser excitation wavelength as well as on the size and period of Au nanoclusters. By tuning the optical resonance conditions a maximal enhancement factor of 2 × 10{sup 4} is achieved. The investigation of surface-enhanced Raman scattering by cobalt phthalocyanine deposited on laterally ordered arrays of paired Au nanoclusters (dimers) reveals anisotropic enhancement with respect to polarization of the scattered light parallel or perpendicular to the dimer axis. - Highlights: • Controllable and reproducible Au nanocluster and dimer arrays were fabricated. • Surface enhanced Raman scattering (SERS) by CuS nanocrystals was observed. • SERS by ultrathin cobalt phthalocyanine (CoPc) films was observed. • Dependence of SERS enhancement factor on the size of Au nanoclusters is resonant. • SERS by ultrathin CoPc films formed on Au dimer arrays is polarization dependent.

  20. Prediction of the shape of inline wave force and free surface elevation using First Order Reliability Method (FORM)

    DEFF Research Database (Denmark)

    Ghadirian, Amin; Bredmose, Henrik; Schløer, Signe

    2017-01-01

    In design of substructures for offshore wind turbines, the extreme wave loads which are of interest in Ultimate Limit States are often estimated by choosing extreme events from linear random sea states and replacing them by either stream function wave theory or the NewWave theory of a certain...... as the free surface elevation time series. The discrepancies between the FORM results and the measurements is found to be a result of more nonlinearity in the selected events than second order and negligence of the drag forces above still water level in the present analysis. This paper is one step toward more...... precise prediction of extreme wave shape and loads. Ultimately such waves can be used in the design process of offshore structures. The approach can be generalized to fully nonlinear models....

  1. Revisiting the vector form factor at next-to-leading order in 1/N{sub C}

    Energy Technology Data Exchange (ETDEWEB)

    Rosell, Ignasi, E-mail: rosell@uch.ceu.e [Departamento de Ciencias Fisicas, Matematicas y de la Computacion, Universidad CEU Cardenal Herrera, c/ Sant Bartomeu 55, E-46115 Alfara del Patriarca, Valencia (Spain); IFIC, Universitat de Valencia - CSIC, Apt. Correus 22085, E-46071 Valencia (Spain)

    2010-10-15

    Using the Resonance Chiral Theory lagrangian, we perform a calculation of the vector form factor of the pion at the next-to-leading order (NLO) in the 1/N{sub C} expansion. Imposing the correct QCD short-distance constraints, one determines it in terms of F, G{sub V}, F{sub A} and resonance masses. Its low momentum expansion fixes then the low-energy chiral couplings L{sub 9} and C{sub 88} -C{sub 90} at NLO, keeping full control of their renormalization scale dependence. At {mu}{sub 0} = 0.77 GeV, we obtain L{sup r}{sub 9}({mu}{sub 0}) = (7.6 {+-} 0.6) . 10{sup -3} and C{sup r}{sub 88}({mu}{sub 0}) -C{sup r}{sub 90}({mu}{sub 0}) = (-4.5 {+-} 0.5) . 10{sup -5}.

  2. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant.

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-06-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.

  3. Guided proliferation and bone-forming functionality on highly ordered large diameter TiO{sub 2} nanotube arrays

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ruopeng; Wu, Hongliu; Ni, Jiahua, E-mail: jiahua.ni@sjtu.edu.cn; Zhao, Changli; Chen, Yifan; Zheng, Chengjunyi; Zhang, Xiaonong, E-mail: xnzhang@sjtu.edu.cn

    2015-08-01

    The significantly enhanced osteoblast adhesion, proliferation and alkaline phosphatase (ALP) activity were observed on TiO{sub 2} nanotube surface in recent studies in which the scale of nanotube diameter was restricted under 100 nm. In this paper, a series of highly ordered TiO{sub 2} nanotube arrays with larger diameters ranging from 150 nm to 470 nm were fabricated via high voltage anodization. The behaviors of MC3T3-E1 cells in response to the diameter-controlled TiO{sub 2} nanotubes were investigated. A contrast between the trend of proliferation and the trend of cell elongation was observed. The highest cell elongation (nearly 10:1) and the lowest cell number were observed on the TiO{sub 2} nanotube arrays with 150 nm diameter. While, the lowest cell elongation and highest cell number were achieved on the TiO{sub 2} nanotube arrays with 470 nm diameter. Furthermore, the ALP activity peaked on the 150 nm diameter TiO{sub 2} nanotube arrays and decreased dramatically with the increase of nanotube diameter. Thus a narrow range of diameter (100–200 nm) that could induce the greatest bone-forming activity is determined. It is expected that more delicate design of orthopedic implant with regional abduction of cell proliferation or bone forming could be achieved by controlling the diameter of TiO{sub 2} nanotubes. - Highlights: • Improved anodization methods leading to more ordered large diameter TiO{sub 2} nanotubes • Significantly enhanced ALP activity was observed on 150 nm diameter TiO{sub 2} nanotubes. • The highest cell density was observed on 470 nm diameter TiO{sub 2} nanotube arrays. • Similar cell response was observed on the amorphous and anatase phased nanotube surface.

  4. Guided proliferation and bone-forming functionality on highly ordered large diameter TiO2 nanotube arrays.

    Science.gov (United States)

    Zhang, Ruopeng; Wu, Hongliu; Ni, Jiahua; Zhao, Changli; Chen, Yifan; Zheng, Chengjunyi; Zhang, Xiaonong

    2015-08-01

    The significantly enhanced osteoblast adhesion, proliferation and alkaline phosphatase (ALP) activity were observed on TiO2 nanotube surface in recent studies in which the scale of nanotube diameter was restricted under 100 nm. In this paper, a series of highly ordered TiO2 nanotube arrays with larger diameters ranging from 150 nm to 470 nm were fabricated via high voltage anodization. The behaviors of MC3T3-E1 cells in response to the diameter-controlled TiO2 nanotubes were investigated. A contrast between the trend of proliferation and the trend of cell elongation was observed. The highest cell elongation (nearly 10:1) and the lowest cell number were observed on the TiO2 nanotube arrays with 150 nm diameter. While, the lowest cell elongation and highest cell number were achieved on the TiO2 nanotube arrays with 470 nm diameter. Furthermore, the ALP activity peaked on the 150 nm diameter TiO2 nanotube arrays and decreased dramatically with the increase of nanotube diameter. Thus a narrow range of diameter (100-200 nm) that could induce the greatest bone-forming activity is determined. It is expected that more delicate design of orthopedic implant with regional abduction of cell proliferation or bone forming could be achieved by controlling the diameter of TiO2 nanotubes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The changes in levels of C-P and insulin in glucose tolerance test in rats with experimental non-insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Liu Xinqiu; Lei Ming

    2001-01-01

    The changes in levels of C-P and insulin were investigated in the GT test in rats with non-insulin dependent diabetes mellitus. In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), the authors injected rats with small dose streptozocoi (i.v.). Two weeks after the injection, the rats developed impaired glucose tolerance (IGT). Then, they were fed with high energy diet for eight weeks to form NIDDM. The results showed that the highest peak time of C-P and insulin in NIDDM was remarkably later than that in normal subjects, the highest peak time was in two hours (P < 0.05). The data suggest that level of C-P could accurately respond to level of insulin, and this experimental non-insulin dependent diabetes mellitus model is ideal

  6. The Barbados Insulin Matters (BIM study: Barriers to insulin therapy among a population-based sample of people with type 2 diabetes in the Caribbean island of Barbados

    Directory of Open Access Journals (Sweden)

    Charles G. Taylor, Jr.

    2017-06-01

    Conclusions: Multiple factors related to patient beliefs and attitudes need to be considered and addressed when initiating insulin in order to minimise psychological insulin resistance and delay. Patients using insulin had less negative perceptions than those not on insulin.

  7. ORAL LONG-ACTING PHARMACEUTICAL FORM OF INSULIN ON THE BASIS OF SELF-ORGANIZING KVASI-LIVING SYSTEM OF COMBINATORIAL PEPTIDES

    Directory of Open Access Journals (Sweden)

    Nosalskaya T.N.,

    2012-06-01

    Full Text Available The paper discusses the results of studies on physical and chemical properties of kvasi-living self-organizing insulin-based system, and on the effectiveness of its oral administration. The purpose of the studies was to modify positively charged amino acid residues into negatively charged residues of dicarboxylic acids. The process of bioorganic combinatorial synthesis produced more than 100 thousand fragments capable of self-organization in the insulin receptor. Self-organization is due to the fact that peptides were previously a part of the whole – namely, insulin molecule. These peptides had small size, and could be easily absorbed by intestines. They also had a long duration of circulation in blood and reacted with insulin receptor in a fashion similar to injected insulin. It is shown that a single oral application of such system leads to statistically significant and sustained reduction in blood glucose levels within 24 hours of application. The effect is observed in both cases: while taking the drug on an empty stomach, and with glucose and food load up to 7.11 mmol / L. A single dose of the drug led to a plateau of stable glucose levels and prevented hypoglycemia and glucose level jumps when applied to rats (control group. The kvasi-living system was obtained by partial proteolysis of recombinant insulin with pepsin, followed by partial modification of peptides with succinic anhydride

  8. Artificial Neural Networks as an Architectural Design Tool-Generating New Detail Forms Based On the Roman Corinthian Order Capital

    Science.gov (United States)

    Radziszewski, Kacper

    2017-10-01

    The following paper presents the results of the research in the field of the machine learning, investigating the scope of application of the artificial neural networks algorithms as a tool in architectural design. The computational experiment was held using the backward propagation of errors method of training the artificial neural network, which was trained based on the geometry of the details of the Roman Corinthian order capital. During the experiment, as an input training data set, five local geometry parameters combined has given the best results: Theta, Pi, Rho in spherical coordinate system based on the capital volume centroid, followed by Z value of the Cartesian coordinate system and a distance from vertical planes created based on the capital symmetry. Additionally during the experiment, artificial neural network hidden layers optimal count and structure was found, giving results of the error below 0.2% for the mentioned before input parameters. Once successfully trained artificial network, was able to mimic the details composition on any other geometry type given. Despite of calculating the transformed geometry locally and separately for each of the thousands of surface points, system could create visually attractive and diverse, complex patterns. Designed tool, based on the supervised learning method of machine learning, gives possibility of generating new architectural forms- free of the designer’s imagination bounds. Implementing the infinitely broad computational methods of machine learning, or Artificial Intelligence in general, not only could accelerate and simplify the design process, but give an opportunity to explore never seen before, unpredictable forms or everyday architectural practice solutions.

  9. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

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

    2014-01-01

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

  10. Insulin Lispro Injection

    Science.gov (United States)

    ... diabetes, insulin lispro is always used with another type of insulin, unless it is used in an external insulin ... diabetes, insulin lispro may be used with another type of insulin or with oral medication(s) for diabetes. Insulin lispro ...

  11. State of insulin self-association does not affect its absorption from the pulmonary route.

    Science.gov (United States)

    Hussain, Alamdar; Ahsan, Fakhrul

    2005-06-01

    This study is designed to compare and contrast the pulmonary absorption profiles of monomeric and hexameric insulin in the presence or absence of ethylene diamine tetraacetic acid (EDTA) or n-tetradecyl-beta-d-maltoside (TDM). The pulmonary absorption of two forms of insulin was studied by monitoring the changes in plasma insulin and glucose levels after intratracheal administration of monomeric or hexameric insulin into anesthetized rodents. EDTA or TDM was added to the formulation in order to evaluate if either of these agents has effects on the rate and extent of pulmonary absorption of monomeric and hexameric insulin. The biochemical changes that may occur after acute administration of TDM-based formulation have also been investigated by estimating lung injury markers in bronchoalveolar lavage fluid. A dose-dependent increase in the plasma insulin and decrease in plasma glucose levels was observed when increasing concentrations of hexameric or monomeric insulin were administered via the pulmonary route. Pulmonary administration of monomeric and hexameric insulin produced comparable absorption profiles in the presence or absence of EDTA or TDM. The bronchoalveolar lavage fluid analysis did not show differences in the levels of injury markers produced in TDM-treated rats and that produced in saline-treated rats, indicating no evidence for adverse effects of TDM in these short-term studies. Overall, in terms of rapidity of action and efficacy to reduce blood sugar, monomeric insulin did not provide advantages over hexameric insulin when administered via the pulmonary route.

  12. Dietary amino acids fed in free form and as protein components do not differently affects postprandial plasma insulin, glucagon, growth hormone and corticosterone responses in rats

    NARCIS (Netherlands)

    Nolles, J.A.; Straten, van E.M.E.; Bremer, B.I.; Koopmanschap, R.E.; Verstegen, M.W.A.; Schreurs, V.V.A.M.

    2006-01-01

    This study examined, whether the postprandial fate of dietary amino acids from different amino acid sources is regulated by the responses of insulin, glucagon, corticosterone and growth hormone (GH). Male Wistar rats were cannulated in the vena jugularis and assigned to dietary groups. The diets

  13. Insulin inhalation: NN 1998.

    Science.gov (United States)

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  14. Estimation of Length and Order of Polynomial-based Filter Implemented in the Form of Farrow Structure

    Directory of Open Access Journals (Sweden)

    S. Vukotic

    2016-08-01

    Full Text Available Digital polynomial-based interpolation filters implemented using the Farrow structure are used in Digital Signal Processing (DSP to calculate the signal between its discrete samples. The two basic design parameters for these filters are number of polynomial-segments defining the finite length of impulse response, and order of polynomials in each polynomial segment. The complexity of the implementation structure and the frequency domain performance depend on these two parameters. This contribution presents estimation formulae for length and polynomial order of polynomial-based filters for various types of requirements including attenuation in stopband, width of transitions band, deviation in passband, weighting in passband/stopband.

  15. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper

    2015-01-01

    The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. The N-terminus of insulin's B......-chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Thus...

  16. EFFICIENCY OF FORMING NUCLEUS COLONIES IN ORDER TO DECREASE POPULATION OF Varroa destructor (ANDRESON AND TRUEMAN, 2000 IN BEEHIVES

    Directory of Open Access Journals (Sweden)

    Zlatko Puškadija

    2003-12-01

    Full Text Available Forming of nucleus colonies is efficient method in growth control of Varroa destructor population. Its goal is to decrease parasite’s pressure on bee colony. The advantage of this bio-technical measurement lays in its implement during vegetation season which delays use of the chemical resources for Varroa destructor control population in beehives for the post major honey harvest period. Nucleus colonies were formed from approx. half of sealed brood (35.5 ± 5.8 dm² and average of 5915 ± 912 bees. Results showed that there were 37.2 ± 5.6% mites removed from parental colonies. Minimum was 30.8%, and maximum was 45.5%. Due to such relatively small efficiency, this method cannot be recommended as unique, but it can be effective if it is applied in the post spring's honey harvest period as a part of growth reduction strategy of Varroa destructor population in beehive.

  17. Insulin Test

    Science.gov (United States)

    ... Syndrome Staph Infections and MRSA Stroke Testicular Cancer Thalassemia Thyroid Cancer Thyroid ... Get Tested? To help evaluate insulin production by the beta cells in the pancreas; to help diagnose the ...

  18. Insulin Basics

    Science.gov (United States)

    ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... be imported for personal use. Inside the pancreas, beta cells make the hormone insulin. With each meal, ...

  19. Association of Physician Orders for Life-Sustaining Treatment Form Use With End-of-Life Care Quality Metrics in Patients With Cancer.

    Science.gov (United States)

    Pedraza, Sandra L; Culp, Stacey; Knestrick, Mark; Falkenstine, Evan; Moss, Alvin H

    2017-10-01

    Many patients with advanced cancer receive aggressive treatment near the end of life. The Physician Orders for Life-Sustaining Treatment (POLST) form is an innovation that converts patient preferences into medical orders. We compared the end-of-life care of patients with advanced cancer who had completed POLST forms with that of patients who had advance directives (ADs). We studied 2,159 West Virginians with ADs and/or POLST forms in the West Virginia e-Directive Registry who died as a result of cancer between January 2011 and February 2016. Data from the Vital Registration Office (date, site, and cause of death) were merged with those from the registry (form type, completion date, and hospice admission). The primary outcome variables were out-of-hospital death (OHD) and hospice admission. The percentage of patients with OHD was 85.7% for patients with POLST forms compared with 72.0% for those with ADs ( P < .001). The odds of OHD for patients with POLST forms were 2.33 times those of patients with ADs. The percentage of patients admitted to hospice was 49.9% for those with POLST forms compared with 27.0% for those with ADs ( P < .001). The odds of being admitted to hospice for patients with POLST forms were 2.69 times those of patients with ADs. Advance care planning with completion of POLST forms compared with ADs in patients with advanced cancer was associated with two quality end-of-life care metrics: OHD and hospice admission. Our study suggests that goals-of-care discussions including POLST form completion may improve end-of-life care for patients with advanced cancer.

  20. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  1. About Some Of The Properties Of A Guest Molecule Confined In A Water Network, In Order To Form A Clathrate

    Science.gov (United States)

    Pérez, G. Bravo; Cruz-Torres, A.; Romero-Martínez, A.

    2008-03-01

    At conditions of high pressure and or low temperature, like a sea bottom from even 1 Km deep, hydrates formation may take place. Its presence is facilitated at the water/oil interface inside conducting oil pipelines. Once formed, the hydrates nucleate further to agglomerations, sticking to the inner surface of the tube. This represents a big problem to flow assurance. We present results contributing to a better understanding of the interaction of a guest molecule with a water cage confining it, that give rise to a hydrate formation. The hydrate structure, its formation energy, and the role that the H bond and its cooperative effect in the water network play in the electrostatic dipole moment of the hydrate, are presented. Molecular calculations using the HF/6-311g(d, p), B3LYP/6-311g(d, p), and B3LYP/6-311++g(d,p) methods, have been applied to compare three different hydrates, each one confining one, two CH4 molecules, and a CO2 molecule, requiring respectively n = 14, 35, and 15 water molecules for the confinement.

  2. [Types of insulin therapy].

    Science.gov (United States)

    Sáez de la Fuente, J; Granja Berna, V; Ferrari Piquero, J M; Valero Zanuy, M A; Herreros de Tejada López-Coterilla, A

    2008-02-01

    Diabetes mellitus is a chronic disease associated with a series of long-term microvascular and macrovascular complications that requires continuing therapeutic control. In recent years, the pharmaceutical industry has developed new types of insulin and administration systems in order to more closely mimic human insulin secretion. In this way, insulin therapy is divided into conventional and intensive regimens according to their complexity. In type 1 diabetes mellitus (T1DM) patients, the treatment of choice is the one which achieves intensive glycemic control. In type 2 diabetes mellitus, we can start with a simplified conventional regimen which could progress into an intensive one similar to that of T1DM treatment. Both types of diabetes require an individualized treatment prescription based on the needs and characteristics of each patient.

  3. Is insulin binding followed by disulfide interchange between insulin and the receptor?

    International Nuclear Information System (INIS)

    Phillips, P.E.; Lipkin, E.W.; Teller, D.C.; de Haeen, C.

    1986-01-01

    The kinetics of insulin binding to rat adipocytes at 15 0 C can best be described by a 2-step model. Insulin, I, first binds to the receptor, R. Occupied receptors, RI, then convert reversibly to another form, R'I, from which insulin cannot dissociate directly. At equilibrium, the R'I:RI ratio is ∼3:2. To elucidate the nature of R'I, the effects of 5,5'-dithiobis-(2-nitrobenzoate) (DTNB) on the kinetics of insulin binding were investigated. DTNB (2.5 mM) added with 1 nM 125 I-iodoinsulin doubled insulin binding relative to cells without DTNB. When labeled insulin prebound to cells was dissociated with excess unlabeled insulin, DTNB added with the unlabeled insulin reduced the amount of dissociating label. Treatment of adipocytes with DTNB prior to insulin exposure did not alter the subsequent response of insulin binding to DTNB. These data suggest that the receptor exists in at least two conformational states: R, the unoccupied receptor, with a cryptic sulfhydryl group, and the occupied receptors RI and R'I, in which a sulfhydryl group is sensitive to DTNB. The authors propose that R'I formation is the result of disulfide exchange between the receptor and insulin, in accordance with the kinetics evidence that insulin cannot directly dissociate from R'I. The disulfide exchange generates a free sulfhydryl on insulin, with which DTNB reacts to trap insulin covalently bound in the R'I form

  4. Bilinear forms, N-soliton solutions and soliton interactions for a fourth-order dispersive nonlinear Schrödinger equation in condensed-matter physics and biophysics

    International Nuclear Information System (INIS)

    Liu, Rong-Xiang; Tian, Bo; Liu, Li-Cai; Qin, Bo; Lü, Xing

    2013-01-01

    In this paper we investigate a fourth-order dispersive nonlinear Schrödinger equation, which governs the dynamics of a one-dimensional anisotropic Heisenberg ferromagnetic spin chain with the octuple–dipole interaction in condensed-matter physics as well as the alpha helical proteins with higher-order excitations and interactions in biophysics. Beyond the existing constraint, upon the introduction of an auxiliary function, bilinear forms and N-soliton solutions are constructed with the Hirota method. Asymptotic analysis on the two-soliton solutions indicates that the soliton interactions are elastic. Soliton velocity varies linearly with the coefficient of discreteness and higher-order magnetic interactions. Bound-state solitons can also exist under certain conditions. Period of a bound-state soliton is inversely correlated to the coefficient of discreteness and higher-order magnetic interactions. Interactions among the three solitons are all pairwise elastic

  5. Diabetes and Insulin

    Science.gov (United States)

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  6. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... in the normal range. What happens with insulin resistance? In insulin resistance, muscle, fat, and liver cells do not ... they do not usually test specifically for insulin resistance. Insulin resistance can be assessed by measuring the level ...

  7. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

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

  8. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

    Directory of Open Access Journals (Sweden)

    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  9. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

    Science.gov (United States)

    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms

    International Nuclear Information System (INIS)

    Haselbacher, G.K.; Schwab, M.E.; Pasi, A.; Humbel, R.E.

    1985-01-01

    Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain

  11. Kinetics of subcutaneous NPH insulin in diabetics

    Energy Technology Data Exchange (ETDEWEB)

    Kolendorf, K.; Bojsen, J.

    1982-04-01

    Kinetics of subcutaneous NPH insulin were studied in newly diagnosed insulin-dependent diabetics. Using a biotelemetric technique with small Geiger-Mueller detectors applied to the skin surface, the disappearance of 125I-NPH insulin fron subcutis was monoexponential with a mean half-life of 6.6 +/- 3.3 (SD) hr. A model is presented to compare the disappearance rates of subcutaneous 125I-NPH insulin and the calculated plasma appearance insulin curve derived from the actual plasma insulin concentration measurements, assuming a one-compartment model and first-order kinetics. Areas under the absorption- and appearance-time curves calculated from external measurements and from plasma insulin concentrations were identical. There was a strong correlation between plasma concentrations and absorbed amounts of labeled insulin (r . 0.8782, P less than 0.001), as there was between the blood glucose-lowering effects and percent absorbed insulin per hour (r . 0.7659, P less than 0.001). Our results indicate that the disappearance rate of iodine-labeled insulin was a relevant biological expression of insulin absorption from subcutis and a reliable noninvasive method of quantitative determination of insulin concentration in blood.

  12. Evaluation of diabetic patients after three month use of continuous subcutaneous insulin infusion, dispensed by a protocolled form at outpatient reference clinic of Taguatinga Regional Hospital.

    Science.gov (United States)

    Miranda, Leonardo Garcia; Pedrosa, Hermelinda Cordeiro; Falleiros, Roberta Kelly Menezes Maciel; Oliveira, Renata de Moraes; Tolentino, Monica; Casulari, Luiz Augusto

    2015-02-01

    To evaluate the data of continuous subcutaneous insulin infusion protocol (CSII) for diabetics waived by the Health State Secretariat of Distrito Federal (HSSDF) and therapeutic responses three months after the transfer of multiple daily injections regimen for CSII. Eighty patients (49 female) took part in this experimental study, mean age and disease duration were 27.9 years and 13 years, respectively; 96% patients had type 1 diabetes mellitus. The entire sample (ECO) and 3 subgroups (group 1 - A1c decrease, group 2 - A1c stable, and group 3 - A1c increase), stratified according to a ≥ 0.5% change in A1c, were analyzed. Group 1 involved 64% of the patients. The ECO showed a significant A1c decrease: MDI 8.1 ± 1.4% vs. CSII 7.3 ± 0.9%, p < 0.0001 (0.8% difference pro CSII therapy). Group 1 demonstrated an A1c decrease from 8.7% to 7.3% (1.4% difference). Group 2 mean A1c was 7.1%. Rate of hypoglycemia (< 50 mg/dL) decreased 61% in the ECO and 79% in Group 2. This study reinforces the safety and efficacy of CSII with a robust A1c reduction and hypoglycemia. The pioneer care HSSDF ambulatory attests to be achievable the free dispensing by Unified Health System (UHS) following a protocol, and this approach results in less wastage to the patient and represents a rational policy of therapy with CSII for UHS.

  13. New Closed-Form Results on Ordered Statistics of Partial Sums of Gamma Random Variables and its Application to Performance Evaluation in the Presence of Nakagami Fading

    KAUST Repository

    Nam, Sung Sik

    2017-06-19

    Complex wireless transmission systems require multi-dimensional joint statistical techniques for performance evaluation. Here, we first present the exact closed-form results on order statistics of any arbitrary partial sums of Gamma random variables with the closedform results of core functions specialized for independent and identically distributed Nakagami-m fading channels based on a moment generating function-based unified analytical framework. These both exact closed-form results have never been published in the literature. In addition, as a feasible application example in which our new offered derived closed-form results can be applied is presented. In particular, we analyze the outage performance of the finger replacement schemes over Nakagami fading channels as an application of our method. Note that these analysis results are directly applicable to several applications, such as millimeter-wave communication systems in which an antenna diversity scheme operates using an finger replacement schemes-like combining scheme, and other fading scenarios. Note also that the statistical results can provide potential solutions for ordered statistics in any other research topics based on Gamma distributions or other advanced wireless communications research topics in the presence of Nakagami fading.

  14. Analysis of a No Equilibrium Linear Resistive-Capacitive-Inductance Shunted Junction Model, Dynamics, Synchronization, and Application to Digital Cryptography in Its Fractional-Order Form

    Directory of Open Access Journals (Sweden)

    Sifeu Takougang Kingni

    2017-01-01

    Full Text Available A linear resistive-capacitive-inductance shunted junction (LRCLSJ model obtained by replacing the nonlinear piecewise resistance of a nonlinear resistive-capacitive-inductance shunted junction (NRCLSJ model by a linear resistance is analyzed in this paper. The LRCLSJ model has two or no equilibrium points depending on the dc bias current. For a suitable choice of the parameters, the LRCLSJ model without equilibrium point can exhibit regular and fast spiking, intrinsic and periodic bursting, and periodic and chaotic behaviors. We show that the LRCLSJ model displays similar dynamical behaviors as the NRCLSJ model. Moreover the coexistence between periodic and chaotic attractors is found in the LRCLSJ model for specific parameters. The lowest order of the commensurate form of the no equilibrium LRCLSJ model to exhibit chaotic behavior is found to be 2.934. Moreover, adaptive finite-time synchronization with parameter estimation is applied to achieve synchronization of unidirectional coupled identical fractional-order form of chaotic no equilibrium LRCLSJ models. Finally, a cryptographic encryption scheme with the help of the finite-time synchronization of fractional-order chaotic no equilibrium LRCLSJ models is illustrated through a numerical example, showing that a high level security device can be produced using this system.

  15. Characteristics of binding of a low affinity, noncooperative insulin [(LeuB25]insulin) to IM-9 lymphocytes

    International Nuclear Information System (INIS)

    Green, A.; Frank, B.H.; Rubenstein, A.; Tager, H.; Olefsky, J.M.

    1983-01-01

    [Leu-B25]insulin is a low affinity insulin analog which does not increase the rate of dissociation of 125 I-insulin from insulin receptors (i.e. does not display negative cooperativity). We have studied the characteristics of binding of this analog to IM-9 cultured lymphocytes, in order to determine the contribution of negative cooperativity to the curvilinear nature of Scatchard plots typical of insulin binding data. The affinity of [LeuB25]insulin for receptors was approximately 1% that of insulin, as determined by its ability to inhibit 125 I-insulin binding. Monoiodinated preparations of insulin and of [LeuB25]insulin were produced, labeled in the tyrosine at position 14 of the A chain. These 125 I-TyrA14-labeled species were used in all studies. Both native insulin and a serum containing antiinsulin receptor antibodies were equally potent at inhibiting binding of 125 I-[LeuB25]insulin and 125 I-native insulin, suggesting that they bind to the same population of receptors. Native insulin (100 ng/ml) increased the rate of dissociation of both 125 I-insulin and 125 I-[LeuB25]insulin. However, [LeuB25]insulin (2.5 micrograms/ml) did not increase the rates of dissociation of either 125 I-insulin or 125 I-[LeuB25]insulin (i.e. it did not display negative cooperativity). Competition curves and Scatchard plots were constructed using 125 I-[LeuB25]insulin and unlabeled analog. Half-maximal inhibition of 125 I-[LeuB25]insulin binding was seen at a [LeuB25]insulin concentration of approximately 500 ng/ml. More importantly, the Scatchard plot of these binding data was markedly curvilinear, as is typical of insulin binding data

  16. A third-order computational method for numerical fluxes to guarantee nonnegative difference coefficients for advection-diffusion equations in a semi-conservative form

    Science.gov (United States)

    Sakai, K.; Watabe, D.; Minamidani, T.; Zhang, G. S.

    2012-10-01

    According to Godunov theorem for numerical calculations of advection equations, there exist no higher-order schemes with constant positive difference coefficients in a family of polynomial schemes with an accuracy exceeding the first-order. We propose a third-order computational scheme for numerical fluxes to guarantee the non-negative difference coefficients of resulting finite difference equations for advection-diffusion equations in a semi-conservative form, in which there exist two kinds of numerical fluxes at a cell surface and these two fluxes are not always coincident in non-uniform velocity fields. The present scheme is optimized so as to minimize truncation errors for the numerical fluxes while fulfilling the positivity condition of the difference coefficients which are variable depending on the local Courant number and diffusion number. The feature of the present optimized scheme consists in keeping the third-order accuracy anywhere without any numerical flux limiter. We extend the present method into multi-dimensional equations. Numerical experiments for advection-diffusion equations showed nonoscillatory solutions.

  17. Plasma insulin disturbances in primary hyperparathyroidism

    Science.gov (United States)

    Kim, Hakjoong; Kalkhoff, Ronald K.; Costrini, Nicholas V.; Cerletty, James M.; Jacobson, Mitchell

    1971-01-01

    Plasma insulin dynamics were evaluated in 10 patients with primary hyperparathyroidism before and after parathyroidectomy and correction of hypercalcemia. Before surgery fasting plasma insulin concentrations and insulin responses to administered glucose, tolbutamide, and glucagon were significantly greater than postoperative values. Hyperinsulinemia was not associated with altered glucose curves during glucose or glucagon tolerance tests, but a relatively greater insulin response to tolbutamide resulted in an increased hypoglycemic effect following its administration. The glucose-lowering action of intravenous insulin was slightly impaired before treatment. Intramuscular injections of parathormone to six normal men for 8 days induced mild hypercalcemia and hypophosphatemia and reproduced augmented plasma insulin responses to oral glucose and intravenous tolbutamide. 4-hr intravenous infusions of calcium to another group of six normal men raised serum calcium concentrations above 11 mg/100 ml. This did not alter glucose or insulin curves during oral glucose tolerance but markedly accentuated insulin responses to tolbutamide and potentiated its hypoglycemic effect. When highly purified parathormone was incubated with isolated pancreatic islets of male rats, glucose-stimulated insulin secretion was unaffected. These findings suggest that chronic hypercalcemia of hyperparathyroidism sustains a form of endogenous insulin resistance that necessitates augmented insulin secretion to maintain plasma glucose homeostasis. This state is insufficient to oppose tolbutamide-induced hypoglycemia because of an additional direct, selective enhancement of hypercalcemia on pancreatic beta cell responsiveness to the sulfonylurea. The possible direct role of parathormone in these events has not been established. PMID:5129311

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

    Science.gov (United States)

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

    2013-08-01

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

  19. D-optimal mixture design: optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms.

    Science.gov (United States)

    El-Malah, Yasser; Nazzal, Sami; Khanfar, Nile M

    2006-01-01

    The objective of the present study was to develop a tablet formulation with a zero-order drug release profile based on a balanced blend of three matrix ingredients. To accomplish this goal, a 17-run, three-factor, two-level D-Optimal mixture design was employed to evaluate the effect of Polyox (X1), Carbopol (X2), and lactose (X3) concentrations on the release rate of theophylline from the matrices. Tablets were prepared by direct compression and were subjected to an in vitro dissolution study in phosphate buffer at pH 7.2. Polynomial models were generated for the responses Y4 (percent released in 8 h) and Y6 (similarity factor or f2). Fitted models were used to predict the composition of a formulation that would have a similar dissolution profile to an ideal zero-order release at a rate of 8.33% per hour. When tested, dissolution profile of the optimized formulation was comparable to the reference profile (f2 was 74.2, and n [release exponent] was 0.9). This study demonstrated that a balanced blend of matrix ingredients could be used to attain a zero-order release profile. Optimization was feasible by the application of response surface methodology, which proved efficient in designing controlled-release dosage forms.

  20. Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine

    NARCIS (Netherlands)

    Birkeland, Kåre I.; Home, Philip D.; Wendisch, Ulrich; Ratner, Robert E.; Johansen, Thue; Endahl, Lars A.; Lyby, Karsten; Jendle, Johan H.; Roberts, Anthony P.; DeVries, J. Hans; Meneghini, Luigi F.

    2011-01-01

    Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1

  1. Insulin Human Inhalation

    Science.gov (United States)

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  2. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  3. Clinical utility of insulin and insulin analogs

    Science.gov (United States)

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  4. Dissecting the role of disulfide bonds on the amyloid formation of insulin

    International Nuclear Information System (INIS)

    Li, Yang; Gong, Hao; Sun, Yue; Yan, Juan; Cheng, Biao; Zhang, Xin; Huang, Jing; Yu, Mengying; Guo, Yu; Zheng, Ling; Huang, Kun

    2012-01-01

    Highlights: ► We dissect how individual disulfide bond affects the amyloidogenicity of insulin. ► A controlled reduction system for insulin is established in this study. ► Disulfide breakage is associated with unfolding and increased amyloidogenicity. ► Breakage of A6-A11 is associated with significantly increased cytotoxicity. ► Analogs without A6-A11 have a higher potency to form high order toxic oligomers. -- Abstract: Disulfide bonds play a critical role in the stability and folding of proteins. Here, we used insulin as a model system, to investigate the role of its individual disulfide bond during the amyloid formation of insulin. Tris(2-carboxyethyl)phosphine (TCEP) was applied to reduce two of the three disulfide bonds in porcine insulin and the reduced disulfide bonds were then alkylated by iodoacetamide. Three disulfide bond-modified insulin analogs, INS-2 (lack of A6-A11), INS-3 (lack of A7-B7) and INS-6 (lack of both A6-A11 and A7-B7), were obtained. Far-UV circular dichroism (CD) spectroscopy results indicated that the secondary structure of INS-2 was the closest to insulin under neutral conditions, followed by INS-3 and INS-6, whereas in an acidic solution all analogs were essentially unfolded. To test how these modifications affect the amyloidogenicity of insulin, thioflavin-T (ThT) fluorescence and transmission electronic microscopy (TEM) were performed. Our results showed that all analogs were more prone to aggregation than insulin, with the order of aggregation rates being INS-6 > INS-3 > INS-2. Cross-linking of unmodified proteins (PICUP) assay results showed that analogs without A6-A11 (INS-2 and INS-6) have a higher potential for oligomerization than insulin and INS-3, which is accompanied with a higher cytotoxicity as the hemolytic assays of human erythrocytes suggested. The results indicated that breakage of A7-B7 induced more unfolding of the insulin structure and a higher amyloidogenicity than breakage of A6-A11, but breakage of A6

  5. Description of Christensenella minuta gen. nov., sp. nov., isolated from human faeces, which forms a distinct branch in the order Clostridiales, and proposal of Christensenellaceae fam. nov.

    Science.gov (United States)

    Morotomi, Masami; Nagai, Fumiko; Watanabe, Yohei

    2012-01-01

    A novel, strictly anaerobic, non-motile, non-spore-forming, Gram-negative, short, straight rod with tapered ends, designated YIT 12065(T), was isolated from human faeces. Strain YIT 12065(T) was saccharolytic and negative for catalase, oxidase and urease, hydrolysis of aesculin and gelatin, nitrate reduction and indole production. The end products of glucose fermentation were acetic acid and a small amount of butyric acid. The DNA G+C content was 51.3 mol%. The predominant fatty acids were iso-C(15:0), C(16:0) and C(14:0). Respiratory quinones were not detected. The cell wall contained glutamic acid, serine, alanine and ll-diaminopimelic acid. The whole-cell sugars were ribose, rhamnose, galactose and glucose. Phylogenetic analyses based on 16S rRNA gene sequences using three treeing algorithms revealed that the strain formed a novel family-level lineage within the phylum Firmicutes, class Clostridia, order Clostridiales. Caldicoprobacter oshimai JW/HY-331(T) was shown to be the closest named relative on the basis of 16S rRNA gene sequence similarity (86.9%), followed by Tindallia californiensis DSM 14871(T) (86.3%) and Clostridium ganghwense JCM 13193(T) (86.1%). Similar 16S rRNA gene sequences (98.6-96.7%) were found amongst faecal uncultured clones of human and dugong (Dugong dugon). They clustered with strain YIT 12065(T) in a distinct and deep evolutionary lineage of descent in the order Clostridiales. The distinct phylogenetic position supports the proposal of Christensenella gen. nov., with the type species Christensenella minuta sp. nov. (type strain YIT 12065(T) =DSM 22607(T) =JCM 16072(T)). A new family Christensenellaceae fam. nov. is also proposed.

  6. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi

    2010-01-01

    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  7. Degludec insulin: A novel basal insulin

    OpenAIRE

    Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

    2011-01-01

    This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

  8. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2010-02-01

    When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

  9. JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.

    Science.gov (United States)

    Yin, T; Tsang, M L; Yang, Y C

    1994-10-28

    Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors. Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes. We further identify the 170-kDa tyrosine-phosphorylated protein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130-kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L protein following ligand-receptor interaction. In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.

  10. Normal growth spurt and final height despite low levels of all forms of circulating insulin-like growth factor-I in a patient with acid-labile subunit deficiency

    DEFF Research Database (Denmark)

    Domené, Horacio M; Martínez, Alicia S; Frystyk, Jan

    2007-01-01

    BACKGROUND: In a recently described patient with acid-labile subunit (ALS) deficiency, the inability to form ternary complexes resulted in a marked reduction in circulating total insulin-like growth factor (IGF)-I, whereas skeletal growth was only marginally affected. To further study the role...... of circulating versus locally produced IGF-I in skeletal growth in this patient, we now describe in detail growth changes and their relationship with several components of the circulating IGF system. DESIGN AND METHODS: We followed growth and development up to the final height in a patient with complete ALS...... and pubertal onset. Six months of GH treatment had no effect on growth. At the age of 19.3 years, he spontaneously completed puberty and had a normal growth spurt for a late adolescent (peak height velocity of 8.4 cm/year). A normal final height was attained at 21.3 years (167.5 cm; -0.78 SDS). During as well...

  11. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  12. [Adverse reactions to insulin].

    Science.gov (United States)

    Liñana, J J; Montoro, F J; Hernández, M D; Basomba, A

    1997-07-01

    The prevalence of allergic reactions to insuline has decreased during the last few years. Probably this is due to the use of the newly-developed recombinant human insuline. At present, adverse reactions to insuline occur in 5-10% of patients on therapy with insuline. Adverse reactions may be local (more frequent) or systemic (rare). Insuline resistance consists in a different type of immunological reaction. Diagnosis of allergy to insuline is based on clinical history and cutaneous and serological tests. Treatment depends upon the severity of the reaction. When insuline is indispensable despite a previous allergic reaction, a desensitization protocol may be implemented.

  13. Insulin causes insulin-receptor internalization in human erythrocyte ghosts.

    OpenAIRE

    Kelleher, R S; Murray, E F; Peterson, S W

    1987-01-01

    The effect of incubation with insulin on insulin-receptor internalization by erythrocyte ghosts was investigated. The number of surface insulin receptors decreased by 30-40% after incubation of ghosts with insulin. Total insulin-receptor binding to solubilized ghosts was the same in insulin-incubated and control ghosts, whereas insulin binding to an internal vesicular fraction was substantially increased in insulin-incubated ghosts. Our findings suggest that erythrocyte-ghost insulin receptor...

  14. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    mean that more patients are willing to start insulin therapy earlier than with conventional SC insulin therapy? With TI we have a product that has improved pharmacological properties (also in comparison to Exubera) for coverage of prandial insulin requirements. Subsequently, in the clinical trials performed, postprandial glycaemic excursions were lower than with SC injection of RHI or rapid-acting insulin analogues. This only in part (if at all) results in an improved metabolic control in general (= lower HbA1c) (see below). The outlook for 2011 is that there are chances that we shall have an inhaled insulin product on the market. Probably also the first OI will be submitted to the regulatory authorities for market approval or will even be available in less regulated markets. In order to select all relevant publications about new ways of insulin delivery I performed a PUBMED search and also checked the table of contents of a number of journals that publish heavily in this area of research as well references in the publications I found for additional references. Selection of the manuscripts from all publications was predominately based on the fact whether they presented data from clinical studies or not. The selected studies were critically reviewed for novelty and appropriate study design etc. In some cases also reviews about a given topic were selected if they provide relevant novel insights. © 2011 Blackwell Publishing Ltd.

  15. Pseudo ?insulin allergy?

    OpenAIRE

    Chettiar, Pradeep Raman; Sanalkumar, Nishanth; John, Mathew

    2008-01-01

    Allergy to human insulin is relatively rare in clinical practice. This report describes a patient referred for suspected ?insulin allergy? due to lesions appearing at all sites of insulin injection. Careful evaluation confirmed contamination of the insulin syringes due to faulty techniques used by the patient. The report discusses the various types of insulin allergies and the need for proper diabetic education to avoid such infections.

  16. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  17. Mechanisms of cross-suppression of TNP-specific plaque forming cell responses by TMA-specific first-order T suppressor factor

    Energy Technology Data Exchange (ETDEWEB)

    Jendrisak, G.S.; Bellone, C.J.

    1986-03-05

    The addition of hybridoma-derived phenyltrimethylammonium (TMA)-specific first-order T suppressor factor (TsF/sub 1/) into cultures containing Brucella abortus coupled with the TMA and trinitrophenol haptens (TMA-BA-TNP) results in the cross-suppression of TNP-specific plaque forming cell (PFC) responses. The suppression mediated by TMA-TsF/sub 1/ is dependent on the presence of T cells and specific antigen (TMA). Subculturing of whole spleen cells with TMA-TsF/sub 1/ and specific soluble antigen (TMA-BSA) is able to induce suppressor T cells which cross-suppress the TNP-specific PFC of spleen cell cultures stimulated with TMA-BA-TNP in an antigen (TMA)-dependent manner at the effector phase of the response. The effector acting T suppressor cells (Tse) are nylon wool nonadherent and appears to require whole spleen cells in responding cultures for suppression, suggesting that the target of the Tse is not the TNP-specific B cell. The authors are presently characterizing the mechanisms of cross-suppression by TMA-TsF/sub 1/ and Tse utilizing the described primary in vitro antibody assay.

  18. Analog computing for a new nuclear reactor dynamic model based on a time-dependent second order form of the neutron transport equation

    International Nuclear Information System (INIS)

    Pirouzmand, Ahmad; Hadad, Kamal; Suh, Kune Y.

    2011-01-01

    This paper considers the concept of analog computing based on a cellular neural network (CNN) paradigm to simulate nuclear reactor dynamics using a time-dependent second order form of the neutron transport equation. Instead of solving nuclear reactor dynamic equations numerically, which is time-consuming and suffers from such weaknesses as vulnerability to transient phenomena, accumulation of round-off errors and floating-point overflows, use is made of a new method based on a cellular neural network. The state-of-the-art shows the CNN as being an alternative solution to the conventional numerical computation method. Indeed CNN is an analog computing paradigm that performs ultra-fast calculations and provides accurate results. In this study use is made of the CNN model to simulate the space-time response of scalar flux distribution in steady state and transient conditions. The CNN model also is used to simulate step perturbation in the core. The accuracy and capability of the CNN model are examined in 2D Cartesian geometry for two fixed source problems, a mini-BWR assembly, and a TWIGL Seed/Blanket problem. We also use the CNN model concurrently for a typical small PWR assembly to simulate the effect of temperature feedback, poisons, and control rods on the scalar flux distribution

  19. The future of basal insulin supplementation.

    Science.gov (United States)

    Simon, Airin C R; DeVries, J Hans

    2011-06-01

    This review presents an overview of the candidates for an improved basal insulin in the pharmaceutical pipeline. The first new basal insulin to enter the market is most likely insulin degludec (IDeg), currently reporting in phase 3 of development, from Novo Nordisk (Bagsvaerd, Denmark). IDeg has a longer duration of action than currently available analogs. Phase 2 studies show comparable efficacy and safety outcomes compared with insulin glargine once daily with less hypoglycemia in type 1 diabetes. The final results of phase 3 studies seem to confirm this, also in type 2 diabetes. Biodel (Danbury, CT) has two long-acting basal insulin formulations in the pipeline, both in the preclinical phase of development: BIOD-Adjustable Basal, a modified formulation of insulin glargine, is available in long-, medium-, and short-acting forms and could be mixed, and BIOD-Smart Basal releases insulin proportional to the subcutaneous glucose concentration. Eli Lilly (Indianapolis, IN) is also developing a basal insulin. Phase 2 trials have been completed, but no results are published yet. Clinical trials with the new patch pump from CeQur (Montreux, Switzerland) have recently started in Europe. This patch pump delivers both basal and bolus doses subcutaneously and is intended for people with type 2 diabetes who need multiple daily injection insulin therapy.

  20. Insulin resistance in porphyria cutanea tarda.

    Science.gov (United States)

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

    1989-06-01

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

  1. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  2. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  3. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...

  4. Immunoreactive insulin and insulin-degrading activity in rat fecal extracts

    International Nuclear Information System (INIS)

    Pillion, D.J.

    1986-01-01

    The insulin-degrading activity and insulin content of aqueous extracts of rat fecal material isolated from the proximal colon were measured by radioimmunoassay in the presence and absence of various inhibitors of proteolysis. In the absence of protease inhibitors, up to 40% of the [ 125 I]-insulin present in radioimmunoassay tubes was degraded to a form that was not precipitated by trichloroacetic acid. In the presence of bacitracin, EDTA or a mixture of protease inhibitors, insulin degradation was diminished to 125 I]-insulin by the aqueous fecal extract was time- and temperature-dependent. Fecal samples obtained from streptozotocin-diabetic rats contained reduced amounts of insulin, suggesting that the fecal insulin was produced partially, but not exclusively, in the pancreas. These results indicate that fecal material in the rat proximal colon contains small amounts of insulin, as well as a rich supply of insulinase activity, and that insulin receptors located on the mucosal surface of proximal colon epithelial cells may be exposed to insulin in vivo

  5. Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue

    Directory of Open Access Journals (Sweden)

    Stephen B. Hughes

    2013-08-01

    Full Text Available The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation, real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/µLand 891 copies/µL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin receptor respectively (95%limit of detection, and efficient: 1.01 for the insulin-like growth factor 1 receptor assay and 0.95 for the insulin receptor assay. The assays had a broad linear range of detection (seven logs for insulin-like growth factor 1 receptor and six logs for insulin receptor. This allowed for analysis of very small amounts of messenger ribonucleic acid. Low concentrations of both insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were detected in endometrium, lung and spleen samples, whilst high concentrations were detected in heart, muscle and kidney samples, this was most likely due to the high level of glucose metabolism and glucose utilisation by these tissues. The assays developed for insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid expression have been shown to work on equine tissue and will contribute to the understanding of insulin and insulin-like growth factor 1

  6. Insulin inhalation for diabetic patients: Nursing considerations

    Directory of Open Access Journals (Sweden)

    Hanan Mohammed Mohammed

    2016-04-01

    Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

  7. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  8. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

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

    2009-01-01

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

  9. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    International Nuclear Information System (INIS)

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-01-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

  10. Insulin Biosynthetic Interaction Network Component, TMEM24, Facilitates Insulin Reserve Pool Release

    Directory of Open Access Journals (Sweden)

    Anita Pottekat

    2013-09-01

    Full Text Available Insulin homeostasis in pancreatic β cells is now recognized as a critical element in the progression of obesity and type II diabetes (T2D. Proteins that interact with insulin to direct its sequential synthesis, folding, trafficking, and packaging into reserve granules in order to manage release in response to elevated glucose remain largely unknown. Using a conformation-based approach combined with mass spectrometry, we have generated the insulin biosynthetic interaction network (insulin BIN, a proteomic roadmap in the β cell that describes the sequential interacting partners of insulin along the secretory axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane protein 24 (TMEM24 that manages glucose-stimulated insulin secretion from a reserve pool of granules, a critical event impaired in patients with T2D. The identification of TMEM24 in the context of a comprehensive set of sequential insulin-binding partners provides a molecular description of the insulin secretory pathway in β cells.

  11. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  12. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin.

    Science.gov (United States)

    Cengiz, Eda; Swan, Karena L; Tamborlane, William V; Sherr, Jennifer L; Martin, Melody; Weinzimer, Stuart A

    2012-04-01

    Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans. Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order. Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04). These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.

  13. Insulin resistance and laminitis in horses

    OpenAIRE

    Horn, Isabella

    2009-01-01

    Laminitis is a common painful condition in horses that often has a poor outcome. The aetiology of laminitis has been widely studied, but still not completely understood. There is some evidence that pasture associated laminitis is one of the most common forms of laminitis , and this is most likely associated with underlying endocrine dysfunction i.e. insulin resistance. However, what the prevalence of insulin resistance in horses presented with laminitis is, that is currently unknown and it ha...

  14. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  15. Insulin-derived amyloidosis

    Directory of Open Access Journals (Sweden)

    Yashdeep Gupta

    2015-01-01

    Full Text Available Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms "insulin amyloidosis". Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014.

  16. Time Resolved Spectroscopic Studies on a Novel Synthesized Photo-Switchable Organic Dyad and Its Nanocomposite Form in Order to Develop Light Energy Conversion Devices.

    Science.gov (United States)

    Dutta Pal, Gopa; Paul, Abhijit; Yadav, Somnath; Bardhan, Munmun; De, Asish; Chowdhury, Joydeep; Jana, Aindrila; Ganguly, Tapan

    2015-08-01

    UV-vis absorption, steady state and time resolved spectroscopic investigations in pico and nanosecond time domain were made in the different environments on a novel synthesized dyad, 3-(2-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl)prop-2-en-1-one (MNTMA) in its pristine form and when combined with gold (Au) nanoparticles i.e., in its nanocomposite structure. Both steady state and time resolved measurements coupled with the DFT calculations performed by using Gaussian 03 suit of software operated in the linux operating system show that though the dyad exhibits mainly the folded conformation in the ground state but on photoexcitation the nanocomposite form of dyad prefers to be in elongated structure in the excited state indicating its photoswitchable nature. Due to the predominancy of elongated isomeric form of the dyad in the excited state in presence of Au Nps, it appears that the dyad MNTMA may behave as a good light energy converter specially in its nanocomposite form. As larger charge separation rate (kcs ~ 4 x 10(8) s-1) is found relative to the rate associated with the energy wasting charge recombination processes (kcR ~ 3 x 10(5) s-1) in the nanocomposite form of the dyad, it demonstrates the suitability of constructing the efficient light energy conversion devices with Au-dyad hybrid nanomaterials.

  17. A Dual Modulated Homochiral Helical Nanofilament Phase with Local Columnar Ordering Formed by Bent Core Liquid Crystals: Effects of Molecular Chirality.

    Science.gov (United States)

    Li, Lin; Salamonczyk, Miroslaw; Jákli, Antal; Hegmann, Torsten

    2016-08-01

    Helical nanofilament (HNF) phases form as a result of an intralayer mismatch between top and bottom molecular halves in bent-core liquid crystals (BC-LCs) that is relieved by local saddle-splay geometry. HNFs are immensely attractive for photovoltaic and chiral separation applications and as templates for the chiral spatial assembly of guest molecules. Here, the synthesis and characterization of two unichiral BC-LCs and one racemic mixture with tris-biphenyl-diester cores featuring chiral (R,R) and (S,S) or racemic 2-octyloxy aliphatic side chains are presented. In comparison to the achiral compound with linear side chains forming an intralayer modulated HNF phase (HNFmod ), synchrotron small angle X-ray diffraction indicates that the unichiral derivatives form a dual modulated HNF phase with intra- as well as interlayer modulations (HNFmod2 ) suggesting a columnar local structure of the nanofilaments. Transmission electron microscopy and circular dichroism spectropolarimetry confirm that the unichiral materials exclusively form homochiral HNFs with a twist sense-matching secondary twist. A contact preparation provides the first example of two identical chiral liquid crystal phases only differing in their handedness that do not mix and form an achiral liquid crystal phase with an entirely different structure in the contact zone. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Quantitative Estimation of Insulin Sensitivity in Type 1 Diabetic Subjects Wearing a Sensor-Augmented Insulin Pump

    Science.gov (United States)

    Schiavon, Michele; Dalla Man, Chiara; Kudva, Yogish C.; Basu, Ananda; Cobelli, Claudio

    2014-01-01

    OBJECTIVE The goal was to develop a new index of insulin sensitivity in patients with type 1 diabetes estimated from continuous glucose monitoring (CGM) and subcutaneous insulin delivery data under carefully controlled conditions. RESEARCH DESIGN AND METHODS The database consists of 12 subjects with type 1 diabetes, studied during breakfast, lunch, and dinner, in a clinical research unit, wearing both subcutaneous insulin pump and CGM device. Frequent blood samples were drawn for measurements of plasma glucose and insulin concentrations in order to estimate insulin sensitivity with the oral minimal model (SIMM). The new index of insulin sensitivity (SISP) was calculated with a simple algebraic formula for each meal, using only CGM and insulin pump data and compared with SIMM. RESULTS SISP was well correlated with SIMM (r = 0.825; P insulin sensitivity in subjects with type 1 diabetes on sensor-augmented insulin pump therapy has been presented. This new index correlates well with the reference oral minimal model estimate of insulin sensitivity. The knowledge of patient-specific insulin sensitivity and its diurnal variation can help in optimizing insulin therapy in type 1 diabetes and could also inform next-generation closed-loop control systems. PMID:24319120

  19. Insulin Aspart (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin aspart is usually used with another type of insulin, unless it is used in an external insulin ... insulin aspart also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin aspart ...

  20. An immunochemical method for the quantitation of insulin antibodies

    International Nuclear Information System (INIS)

    Reeves, W.G.; Kelly, U.

    1980-01-01

    A 125 I-labelled insulin binding assay is described in which IgG antibody is precipitated by the addition of an optimal concentration of second antibody. Other features include the removal of unlabelled insulin from test sera prior to assay and the use of 22 Na as a volume marker. This approach overcomes problems associated with previous assays for insulin antibodies. Clear differences are seen in the IgG insulin binding capacity (IBC) of sera from patients with insulin resistance and injection site lipo-atrophy when compared with insulin-treated diabetics who lack such complications. The precision and flexibility of this technique make it particularly suitable for studies of the immune response to different species and forms of insulin. (Auth.)

  1. Inkjet printing of insulin microneedles for transdermal delivery.

    Science.gov (United States)

    Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

    2015-08-01

    Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

  2. 41 CFR 102-36.125 - How do we process a Standard Form 122 (SF 122), Transfer Order Excess Personal Property, through...

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false How do we process a... Excess Personal Property For Our Agency Processing Transfers § 102-36.125 How do we process a Standard.... Standard Forms 7 FMP Ft. Worth, TX 76102. Vessels, civilian 4 FD Atlanta, GA 30365. Vessels, DOD 3 FPD...

  3. High order methods for the integration of the Bateman equations and other problems of the form of y‧ = F(y,t)y

    Science.gov (United States)

    Josey, C.; Forget, B.; Smith, K.

    2017-12-01

    This paper introduces two families of A-stable algorithms for the integration of y‧ = F (y , t) y: the extended predictor-corrector (EPC) and the exponential-linear (EL) methods. The structure of the algorithm families are described, and the method of derivation of the coefficients presented. The new algorithms are then tested on a simple deterministic problem and a Monte Carlo isotopic evolution problem. The EPC family is shown to be only second order for systems of ODEs. However, the EPC-RK45 algorithm had the highest accuracy on the Monte Carlo test, requiring at least a factor of 2 fewer function evaluations to achieve a given accuracy than a second order predictor-corrector method (center extrapolation / center midpoint method) with regards to Gd-157 concentration. Members of the EL family can be derived to at least fourth order. The EL3 and the EL4 algorithms presented are shown to be third and fourth order respectively on the systems of ODE test. In the Monte Carlo test, these methods did not overtake the accuracy of EPC methods before statistical uncertainty dominated the error. The statistical properties of the algorithms were also analyzed during the Monte Carlo problem. The new methods are shown to yield smaller standard deviations on final quantities as compared to the reference predictor-corrector method, by up to a factor of 1.4.

  4. Het instellen op insuline van patiënten met diabetes mellitus type 2: In een transmurale organisatievorm minstens even effectief als poliklinisch; een retrospectief onderzoek met 4 jaar follow-up [Initiating insulin therapy in patients with diabetes mellitus type 2: In a transmural form of care at least as effective as an outpatients form; a retrospective study with a 4-year follow-up

    NARCIS (Netherlands)

    Rosendal, H.; Vondeling, H.; Witte, L.P. de; Hutubessy, R.C.W.; Beekum, W.T. van; Heine, R.J.

    2002-01-01

    Objective. Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. Design. Retrospective comparative cohort study. Method. In 1997 data were

  5. Lipodystrophy: Syndrome of severe insulin resistance.

    Science.gov (United States)

    Bindlish, Shagun; Presswala, Lubaina S; Schwartz, Frank

    2015-06-01

    Lipodystrophy (LD) is a relatively rare complex collection of diseases that can be congenital or acquired. It is commonly missed in the clinical setting. Thus, the spectrum of disease presentation mandates clinician expertise in the pathophysiology and management of all forms of LD, obesity, and insulin resistance. An extensive literature search of clinical trials, systematic reviews, and narrative reviews was completed in PubMed for the years 1970 to 2013. The search terms were lipodystrophy, congenital LD, acquired LD, HIV-associated LD, severe insulin resistance, adiposity, obesity, and dyslipidemia. Lipodystrophies are a heterogeneous group of disorders with abnormal adipose tissue distribution, utilization, and metabolism. Adipose tissue can undergo significant changes in composition (hypertrophy and atrophy) in response to a nutritional state. Paradoxically, both excess and deficient adipose tissue is associated with insulin resistance and the metabolic syndrome. Bone density scan (DEXA) for body fat composition analysis or magnetic resonance imaging are optimal modalities for the assessment of abnormal adipose tissue distribution. Ongoing clinical studies suggest thiazolidinediones, insulin like growth factor-1, leptin, and growth hormone-releasing hormone as possible treatment for LPD; however, none of them is approved to reverse fat loss or treat severe insulin resistance due to LPD. The underlying mechanisms for LPD causing insulin resistance may be lipotoxicity and derangements in adipose tissue-derived proteins (adipocytokines). However, the lack of evidence to support this model means that clinicians are on their own as they navigate through the phenotypic presentation of lipodystrophies, obesity, insulin resistance, and the metabolic syndrome.

  6. Insulin in the brain: there and back again.

    Science.gov (United States)

    Banks, William A; Owen, Joshua B; Erickson, Michelle A

    2012-10-01

    Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule. Brain endothelial cells (BECs), the cells that form the vascular BBB and contain the transporter that translocates insulin from blood to brain, are themselves regulated by insulin. The insulin transporter is altered by physiological and pathological factors including hyperglycemia and the diabetic state. The latter can lead to BBB disruption. Pericytes, pluripotent cells in intimate contact with the BECs, protect the integrity of the BBB and its ability to transport insulin. Most of insulin's known actions within the CNS are mediated through two canonical pathways, the phosphoinositide-3 kinase (PI3)/Akt and Ras/mitogen activated kinase (MAPK) cascades. Resistance to insulin action within the CNS, sometimes referred to as diabetes mellitus type III, is associated with peripheral insulin resistance, but it is possible that variable hormonal resistance syndromes exist so that resistance at one tissue bed may be independent of that at others. CNS insulin resistance is associated with Alzheimer's disease, depression, and impaired baroreceptor gain in pregnancy. These aspects of CNS insulin action and the control of its entry by the BBB are likely only a small part of the story of insulin within the brain. Published by Elsevier Inc.

  7. Quantifying Na(I)-insulin and K(I)-insulin non-covalent complexes by ESI-MS method and calculation of their equilibrium constants.

    Science.gov (United States)

    Gülfen, Mustafa; Özdemir, Abdil; Lin, Jung-Lee; Chen, Chung-Hsuan

    2017-10-01

    In this study, the dissociation and formation equilibrium constants of Na(I)-insulin and K(I)-insulin complexes have been calculated after the quantifying them on ESI mass spectrometer. The ESI-MS spectra of the complexes were measured by using the solvents as 50% MeOH in water and 100% water. The effect of pH on the Na(I)-insulin and K(I)-insulin complex formation were examined. Serial binding of Na(I) and K(I) ions to the insulin molecule were observed in the ESI-MS measurements. The first formation equilibrium constants were calculated as K f1 : 5.48×10 3 1/M for Na(I)-insulin complex and K f1 : 4.87×10 3 1/M for K(I)-insulin in water. The binding capability of Na(I) ions to insulin molecule is higher than the capability of K(I) ions. In case of a comparison together with Ca(II)-insulin and Mg(II)-insulin, the formation equilibrium constants (K f1 ) are in order of Ca(II)-insulin>Mg(II)-insulin>Na(I)-insulin>K(I)-insulin in water. The results showed that Na(I) and K(I) ions are involved in the formation of the non-covalent complexes with insulin molecule, since high extracellular and intracellular concentrations of them in the body. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    OpenAIRE

    Radermecker, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  9. Formulation and in vitro evaluation of highly dispersive insulin dry powder formulations for lung administration.

    Science.gov (United States)

    Depreter, Flore; Amighi, Karim

    2010-11-01

    The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. A physiological lipid composition based on a mixture of cholesterol and phospholipids was used to form the coating film around micronised drug particles. The production technique and excipients were chosen in order to limit the degradation of the active ingredient. The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs, and good aerodynamic features were obtained for the different formulations tested, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic behaviour, and the coated formulations also exhibited a decreased residual moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should improve the long-term stability of the protein formulations. No degradation of the insulin molecule occurred during the HPH/spray-drying process, as it was shown using an HPLC method (insulin content between 98.4% and 100.5%), and the content in high molecular weight proteins, assessed using a gel filtration method, stayed below 0.4%. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Insulin pump therapy: what is the evidence for using different types of boluses for coverage of prandial insulin requirements?

    Science.gov (United States)

    Heinemann, Lutz

    2009-11-01

    Bolus infusion of insulin along with a meal is a standard procedure with continuous subcutaneous insulin infusion. Modern insulin pumps allow applying this bolus in four different ways: infusion of the total dose at once or splitting the dose into two boluses, infusion of a part of the bolus in the usual manner plus infusion of the other part over a prolonged period of time (with a higher infusion rate than the basal rate), or infusion of the total dose in the form of an elevated basal rate. Depending on the composition of the given meal and its glycemic index, this is an attempt to match the circulating insulin levels to the rate of glucose absorption from the gut in order to minimize postprandial glycemic excursions. However, in the framework of evidence-based medicine, the benefits of this approach should be proven in appropriately designed clinical studies. Performance of meal-related studies requires careful attention to many aspects in order to allow meaningful evaluation of a given intervention (i.e., type of bolus). Critical evaluation of the clinical experimental studies and the one clinical study published about the impact of different types of boluses on postprandial metabolic control revealed fundamental shortcomings in study design and performance in these studies. Insufficient establishment of comparable preprandial glycemia and insulinemia on the different study days within and between the patients studied is one key aspect. Therefore, the recommendation made in most of these studies (i.e., use of dual-wave bolus) has to be accepted with care, until we have better evidence.

  11. A model to estimate insulin sensitivity in dairy cows

    Directory of Open Access Journals (Sweden)

    Holtenius Kjell

    2007-10-01

    Full Text Available Abstract Impairment of the insulin regulation of energy metabolism is considered to be an etiologic key component for metabolic disturbances. Methods for studies of insulin sensitivity thus are highly topical. There are clear indications that reduced insulin sensitivity contributes to the metabolic disturbances that occurs especially among obese lactating cows. Direct measurements of insulin sensitivity are laborious and not suitable for epidemiological studies. We have therefore adopted an indirect method originally developed for humans to estimate insulin sensitivity in dairy cows. The method, "Revised Quantitative Insulin Sensitivity Check Index" (RQUICKI is based on plasma concentrations of glucose, insulin and free fatty acids (FFA and it generates good and linear correlations with different estimates of insulin sensitivity in human populations. We hypothesized that the RQUICKI method could be used as an index of insulin function in lactating dairy cows. We calculated RQUICKI in 237 apparently healthy dairy cows from 20 commercial herds. All cows included were in their first 15 weeks of lactation. RQUICKI was not affected by the homeorhetic adaptations in energy metabolism that occurred during the first 15 weeks of lactation. In a cohort of 24 experimental cows fed in order to obtain different body condition at parturition RQUICKI was lower in early lactation in cows with a high body condition score suggesting disturbed insulin function in obese cows. The results indicate that RQUICKI might be used to identify lactating cows with disturbed insulin function.

  12. Starting Insulin in Type 2 Diabetes: Real-World Outcomes After the First 12?Months of Insulin Therapy in a New Zealand Cohort

    OpenAIRE

    Sehgal, Shekhar; Khanolkar, Manish

    2015-01-01

    Aims Currently, there is no consensus on which form of insulin to use when initiating insulin in type 2 diabetes (T2D). Our aim was to compare glycated hemoglobin (HbA1C) reduction, weight change and severe hypoglycemia rates during the first year after initiation of intermediate-acting insulin isophane, insulin glargine and pre-mixed insulin in patients with T2D. Methods Electronic clinical records of patients with T2D, starting insulin at a tertiary referral center in Auckland, New Zealand,...

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  14. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  15. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  16. [Hypertension and insulin resistance].

    Science.gov (United States)

    Voiculescu, A; Kutkuhn, B; Rösen, P; Grabensee, B

    1997-10-17

    Non insulin dependent diabetes mellitus (NIDDM) and obesity are defined as classical insulin resistant states. Essential hypertension is now also considered to be an insulin resistant state, even in absence of NIDDM or obesity, as shown in epidemiological, clinical and experimental studies. Neither the underlying mechanism nor a direct causality between the two phenomena has been detected as yet, but different hypotheses have been postulated where, on the one hand, insulin resistance and hypertension are considered to be causally related and, on the other hand, they are considered to be parallel phenomena due to genetic and acquired factors. The clarification of the connection between hypertension and insulin resistance seems to be of great clinical importance, since they are both independent risk factors for cardiovascular disease and mortality from cardiovascular complications. This paper gives an overview of the results of recent research on the possible underlying pathogenetic mechanisms linking hypertension and insulin resistance.

  17. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS......OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...

  18. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

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

  19. Generation of Insulin-Producing Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells: Comparison of Three Differentiation Protocols

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Gabr

    2014-01-01

    Full Text Available Introduction. Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs to form insulin-producing cells (IPCs. We compared the relative efficiency of three differentiation protocols. Methods. Human bone marrow-derived MSCs (HBM-MSCs were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol, trichostatin-A-based (two-step protocol, and β-mercaptoethanol-based (three-step protocol. At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. Results. By immunolabeling, the proportion of generated IPCs was modest (≃3% in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. Conclusion. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.

  20. Future of Automated Insulin Delivery Systems.

    Science.gov (United States)

    Castle, Jessica R; DeVries, J Hans; Kovatchev, Boris

    2017-06-01

    Advances in continuous glucose monitoring (CGM) have brought on a paradigm shift in the management of type 1 diabetes. These advances have enabled the automation of insulin delivery, where an algorithm determines the insulin delivery rate in response to the CGM values. There are multiple automated insulin delivery (AID) systems in development. A system that automates basal insulin delivery has already received Food and Drug Administration approval, and more systems are likely to follow. As the field of AID matures, future systems may incorporate additional hormones and/or multiple inputs, such as activity level. All AID systems are impacted by CGM accuracy and future CGM devices must be shown to be sufficiently accurate to be safely incorporated into AID. In this article, we summarize recent achievements in AID development, with a special emphasis on CGM sensor performance, and discuss the future of AID systems from the point of view of their input-output characteristics, form factor, and adaptability.

  1. 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

  2. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.

    Science.gov (United States)

    Ryu, Jiyoon; Galan, Amanda K; Xin, Xiaoban; Dong, Feng; Abdul-Ghani, Muhammad A; Zhou, Lijun; Wang, Changhua; Li, Cuiling; Holmes, Bekke M; Sloane, Lauren B; Austad, Steven N; Guo, Shaodong; Musi, Nicolas; DeFronzo, Ralph A; Deng, Chuxia; White, Morris F; Liu, Feng; Dong, Lily Q

    2014-05-22

    Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  3. APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor

    Directory of Open Access Journals (Sweden)

    Jiyoon Ryu

    2014-05-01

    Full Text Available Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2 to the insulin receptor (IR is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.

  4. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  5. Insulin and the brain.

    Science.gov (United States)

    Derakhshan, Fatemeh; Toth, Cory

    2013-03-01

    Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

  6. Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nazia Raja-Khan

    2008-01-01

    Full Text Available Nazia Raja-Khan, Sarah S Warehime, Robert A GabbayDivision of Endocrinology, Diabetes, and Metabolism, Penn State Institute for Diabetes and Obesity, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USABackground: Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.Objective: Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.Methods: A MEDLINE search was conducted using the terms “biphasic insulin aspart” to identify clinical studies and reviews.Results: Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.Conclusion: Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.Keywords: biphasic insulin aspart, insulin, diabetes

  7. High electric conductivity of liquid crystals formed by ordered self-assembly of nonionic surfactant N,N-bis(2-hydroxyethyl)dodecanamide in water.

    Science.gov (United States)

    Zhang, Yan; Li, Dechun; Li, Yaping; Zhang, Sen; Wang, Meng; Li, Ying

    2015-03-07

    This work reports the ordered self-assembly of nonconductive small molecules that achieved extra high conductivity, thereby stating an convenient approach for constructing a biofriendly soft material that is suitable to be used as implantable biosensors and electro-stimulated drug delivery systems. The microstructure and the conductive mechanism were investigated in detail by combining experimental methods and molecular simulation. This research demonstrated that self-assembly of amide groups with delocalized electrons into π-stacked arrays exhibited high mobilities for charge carriers. The excellent biocompatibility and processability of soft materials such as liquid crystals ensure that the system has high potential in the advance fields of biosensors and drug delivery devices.

  8. Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

    Directory of Open Access Journals (Sweden)

    Pilvi Taru K

    2009-10-01

    Full Text Available Abstract Background The glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied. Methods In the present study, we investigated the effects of 1 a lactose-free milk drink, 2 a novel fibre-enriched, fat- and lactose-free milk drink and 3 normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline. Results The insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, P = 0.007. There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products. Conclusion The present results suggest that this novel milk drink could have positive effects on insulin response.

  9. Formation of low-dimensional crystalline nucleus region during insulin amyloidogenesis process

    Energy Technology Data Exchange (ETDEWEB)

    Amdursky, Nadav; Gazit, Ehud [Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); Rosenman, Gil, E-mail: gilr@eng.tau.ac.il [School of Electrical Engineering, Iby and Aladar Fleischman, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer We observe lag-phase crystallization process in insulin. Black-Right-Pointing-Pointer The crystallization is a result of the formation of higher order oligomers. Black-Right-Pointing-Pointer The crystallization also changes the secondary structure of the protein. Black-Right-Pointing-Pointer The spectroscopic signature can be used for amyloid inhibitors assay. -- Abstract: Insulin, as other amyloid proteins, can form amyloid fibrils at certain conditions. The self-assembled aggregation process of insulin can result in a variety of conformations, starting from small oligomers, going through various types of protofibrils, and finishing with bundles of fibrils. One of the most common consensuses among the various self-assembly processes that are suggested in the literature is the formation of an early stage nucleus conformation. Here we present an additional insight for the self-assembly process of insulin. We show that at the early lag phase of the process (prior to fibril formation) the insulin monomers self-assemble into ordered nanostructures. The most notable feature of this early self-assembly process is the formation of nanocrystalline nucleus regions with a strongly bound electron-hole confinement, which also change the secondary structure of the protein. Each step in the self-assembly process is characterized by an optical spectroscopic signature, and possesses a narrow size distribution. By following the spectroscopic signature we can measure the potency of amyloid fibrils inhibitors already at the lag phase. We further demonstrate it by the use of epigallocatechin gallate, a known inhibitor for insulin fibrils. The findings can result in a spectroscopic-based application for the analysis of amyloid fibrils inhibitors.

  10. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of ...

  11. Insulin in the Brain: There and Back Again

    Science.gov (United States)

    Banks, William A.; Owen, Joshua B.; Erickson, Michelle A

    2012-01-01

    Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule. Brain endothelial cells (BEC), the cells that form the vascular BBB and contain the transporter that translocates insulin from blood to brain, is itself regulated by insulin. The insulin transporter is altered by physiological and pathological factors including hyperglycemia and the diabetic state. The latter can lead to BBB disruption. Pericytes, pluripotent cells in intimate contact with the BEC, protect the integrity of the BBB and its ability to transport insulin. Most of insulin’s known actions within the CNS are mediated through two canonical pathways, the phosphoinositide-3 kinase (PI3)/Akt and Ras/mitogen activated kinase (MAPK) cascades. Resistance to insulin action within the CNS, sometimes referred to as diabetes mellitus type III, is associated with peripheral insulin resistance, but it is possible that variable hormonal resistance syndromes exist so that resistance at one tissue bed may be independent of that at others. CNS insulin resistance is associated with Alzheimer’s disease, depression, and impaired baroreceptor gain in pregnancy. These aspects of CNS insulin action and the control of its entry by the BBB are likely only a small part of the story of insulin within the brain. PMID:22820012

  12. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    Full Text Available Recently, the prevalence of type 2 diabetes has reached pandemic levels all over the world, and the problem is still growing. Type 2 diabetes is a progressive disease, in which insulin resistance and decrease in beta cell function accompany obesity. Early disorder, which ensues in clinical progression of the disease, is the defect of early phase insulin secretion. Patients have already lost approximately half of their beta cell reserve at the time of diagnosis. Aims of type 2 diabetes treatment are to eliminate hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, to slow down beta cell destruction/depletion, to improve concomitant metabolic problems and to prevent complications. In treatment algorithms, insulin is evaluated as a replacement therapy at the following stage after life style changes (medical nutrition therapy, exercise and oral anti-diabetic drugs (OADs options. Since beta cell depletion is present at initial stages of the disease, it transforms insulin therapy into an earlier approach in treatment stages. Premixed insulin forms are one of the proposed treatment options in patients with hyperglycemia that is not controlled by OADs. These types of insulins are developed to meet both basal and postprandial insulin requirements of patients. Currently, premixed human insulin forms are replaced by analogue insulin forms, which can mimic the physiological secretion in more acceptable manner. Biphasic analogue insulin is one of the readily available pre-mixed analogue insulin forms, an example of this, Biphasic Insulin aspart 30 which is the one of the premixed analoge insulin forms, contains 30% insulin aspart and 70% protaminated insulin aspart. Consensus recommending the individualized approach in insulin therapy implies that physicians should have more detailed information about the use of different insulin forms. Although a global consensus report about initiation, titration and intensification and the use

  13. METABOTROPIC GLUTAMATE TYPE 5, DOPAMINE D2 AND ADENOSINE A2A RECEPTORS FORM HIGHER-ORDER OLIGOMERS IN LIVING CELLS

    Science.gov (United States)

    Cabello, Nuria; Gandía, Jorge; Bertarelli, Daniela C. G.; Watanabe, Masahiko; Lluís, Carme; Franco, Rafael; Ferré, Sergi; Luján, Rafael; Ciruela, Francisco

    2009-01-01

    G protein-coupled receptors are known to form homo- and heteromers at the plasma membrane, but the stoichiometry of these receptor oligomers are relatively unknown. Here, by using bimolecular fluorescence complementation, we visualized for the first time the occurrence of heterodimers of metabotropic glutamate mGlu5 receptors (mGlu5R) and dopamine D2 receptors (D2R) in living cells. Furthermore, the combination of bimolecular fluorescence complementation and bioluminescence resonance energy transfer techniques, as well as the sequential resonance energy transfer (SRET) technique, allowed us to detect the occurrence receptor oligomers containing more than two protomers, mGlu5R, D2R and adenosine A2A receptor (A2AR). Interestingly, by using high-resolution immunoelectron microscopy we could confirm that the three receptors co-distribute within the extrasynaptic plasma membrane of the same dendritic spines of asymmetrical, putative glutamatergic, striatal synapses. Also, co-immunoprecipitation experiments in native tissue demonstrated the existence of an association of mGlu5R, D2R and A2AR in rat striatum homogenates. Overall, these results provide new insights into the molecular composition of G protein-coupled receptor oligomers in general and the mGlu5R/D2R/A2AR oligomer in particular, a receptor oligomer that might constitute an important target for the treatment of some neuropsychiatric disorders. PMID:19344374

  14. Ordering kinetics of lamella-forming block copolymers under the guidance of various external fields studied by dynamic self-consistent field theory.

    Science.gov (United States)

    Wan, Xiaomin; Gao, Tong; Zhang, Liangshun; Lin, Jiaping

    2017-03-01

    Self-consistent field theory with a dynamic extension is exploited to investigate the kinetics of the lamellar formation of symmetric block copolymers under the direction of external fields. In particular, three types of directed self-assembly methods - a permanent field for chemo-epitaxy, a dynamic field for zone annealing and an integrated permanent/dynamic field - are examined. For the chemo-epitaxy involving sparsely prepatterned substrates or zone annealing, the block copolymers generally develop into polycrystalline nanostructures with multiple orientations due to the lack of strong driving forces for eliminating the long-lived imperfections in a limited time. As the integrated chemo-epitaxy and zone annealing method is applied to the block copolymer systems, single-crystalline nanostructures with precisely registered orientations are achieved in a short annealing time owing to the mutual acceleration of defect annihilations, which cannot be produced by the conventional techniques alone. Furthermore, the integrated method allows the rapid fabrication of well-ordered nanostructures on the extremely sparse prepatterned substrates. Our theoretical work may serve to rationalize the faster modern nanolithographic fabrication of smaller microelectronic components using lower-spatial-frequency templates.

  15. Higher-order Zeeman and spin terms in the electron paramagnetic resonance spin Hamiltonian; their description in irreducible form using Cartesian, tesseral spherical tensor and Stevens' operator expressions

    International Nuclear Information System (INIS)

    McGavin, Dennis G; Tennant, W Craighead

    2009-01-01

    In setting up a spin Hamiltonian (SH) to study high-spin Zeeman and high-spin nuclear and/or electronic interactions in electron paramagnetic resonance (EPR) experiments, it is argued that a maximally reduced SH (MRSH) framed in tesseral combinations of spherical tensor operators is necessary. Then, the SH contains only those terms that are necessary and sufficient to describe the particular spin system. The paper proceeds then to obtain interrelationships between the parameters of the MRSH and those of alternative SHs expressed in Cartesian tensor and Stevens operator-equivalent forms. The examples taken, initially, are those of Cartesian and Stevens' expressions for high-spin Zeeman terms of dimension BS 3 and BS 5 . Starting from the well-known decomposition of the general Cartesian tensor of second rank to three irreducible tensors of ranks 0, 1 and 2, the decomposition of Cartesian tensors of ranks 4 and 6 are treated similarly. Next, following a generalization of the tesseral spherical tensor equations, the interrelationships amongst the parameters of the three kinds of expressions, as derived from equivalent SHs, are determined and detailed tables, including all redundancy equations, set out. In each of these cases the lowest symmetry, 1-bar Laue class, is assumed and then examples of relationships for specific higher symmetries derived therefrom. The validity of a spin Hamiltonian containing mixtures of terms from the three expressions is considered in some detail for several specific symmetries, including again the lowest symmetry. Finally, we address the application of some of the relationships derived here to seldom-observed low-symmetry effects in EPR spectra, when high-spin electronic and nuclear interactions are present.

  16. Dimethyl Sulfoxide Induced Destabilization and Disassembly of Various Structural Variants of Insulin Fibrils Monitored by Vibrational Circular Dichroism.

    Science.gov (United States)

    Zhang, Ge; Babenko, Viktoria; Dzwolak, Wojciech; Keiderling, Timothy A

    2015-12-15

    Dimethyl sulfoxide (DMSO) induced destabilization of insulin fibrils has been previously studied by Fourier transform infrared spectroscopy and interpreted in terms of secondary structural changes. The variation of this process for fibrils with different types of higher-order morphological structures remained unclear. Here, we utilize vibrational circular dichroism (VCD), which has been reported to provide a useful biophysical probe of the supramolecular chirality of amyloid fibrils, to characterize changes in the macroscopic chirality following DMSO-induced disassembly for two types of insulin fibrils formed under different conditions, at different reduced pH values with and without added salt and agitation. We confirm that very high concentrations of DMSO can disaggregate both types of insulin fibrils, which initially maintained a β-sheet conformation and eventually changed their secondary structure to a disordered form. The two types responded to varying concentrations of DMSO, and disaggregation followed different mechanisms. Interconversion of specific insulin fibril morphological types also occurred during the destabilization process as monitored by VCD. With transmission electron microscopy, we were able to correlate the changes in VCD sign patterns to alteration of morphology of the insulin fibrils.

  17. Insulin in ramadan.

    Science.gov (United States)

    Kalra, Sanjay; Jawad, Fatema

    2015-05-01

    Many people with diabetes, both type 1 and type 2, require insulin for maintainance of glycaemic control and health. Most of these people can observe the Ramadan fast, provided appropriate dosage adjustments are made, and basic rules of safety followed. This article describes modifications and precautions that are needed while prescribing insulin during Ramadan.

  18. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    -called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

  19. Oral insulin-mimetic compounds that act independently of insulin.

    Science.gov (United States)

    García-Vicente, Silvia; Yraola, Francesc; Marti, Luc; González-Muñoz, Elena; García-Barrado, María José; Cantó, Carles; Abella, Anna; Bour, Sandy; Artuch, Rafael; Sierra, Cristina; Brandi, Nuria; Carpéné, Christian; Moratinos, Julio; Camps, Marta; Palacín, Manuel; Testar, Xavier; Gumà, Anna; Albericio, Fernando; Royo, Miriam; Mian, Alec; Zorzano, Antonio

    2007-02-01

    The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance.

  20. [Insulin resistance in children].

    Science.gov (United States)

    Stąpor, Natalia; Beń-Skowronek, Iwona

    2015-01-01

    Insulin resistance is the state of reduced tissue sensitivity to insulin. The frequency of this occurrence is increasing dramatically in developed countries. Both, environmental and genetic factors are involved in the pathogenesis of insulin resistance. Sedentary lifestyle and the excessive calorie intake cause the substantial increase of the fat issue, leading to overweight and obesity. Insulin resistance occurs physiologically during puberty, but it is also a pathological condition predisposing children to develop abnormal glucose tolerance, diabetes, hypertension and polycystic ovary syndrome among girls. More frequent occurrence of metabolic syndrome can be observed among children born small for gestational age (SGA). The article presents the current views on risk factors, etiology, diagnosis and consequences insulin resistance and disorders of glucose tolerance. © Polish Society for Pediatric Endocrinology and Diabetology.

  1. Newton Leibniz integration for ket-bra operators in quantum mechanics (V)—Deriving normally ordered bivariate-normal-distribution form of density operators and developing their phase space formalism

    Science.gov (United States)

    Fan, Hong-yi

    2008-06-01

    We show that Newton-Leibniz integration over Dirac's ket-bra projection operators with continuum variables, which can be performed by the technique of integration within ordered product (IWOP) of operators [Hong-yi Fan, Hai-liang Lu, Yue Fan, Ann. Phys. 321 (2006) 480], can directly recast density operators and generalized Wigner operators into normally ordered bivariate-normal-distribution form, which has resemblance in statistics. In this way the phase space formalism of quantum mechanics can be developed. The Husimi operator, entangled Husimi operator and entangled Wigner operator for entangled particles with different masses are naturally introduced by virtue of the IWOP technique, and their physical meanings are explained.

  2. Differential effects of insulin injections and insulin infusions on levels ...

    African Journals Online (AJOL)

    Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

  3. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...... and concepts from real designs by studying form in abstract contexts. The challenge for the first approach is how to support students in decoupling form from the work as a whole. The challenge for the second approach is how to translate general form into real design. Hence, choosing between the two approaches...

  4. Frederick Banting and Insulin Discovery (75th Anniversary of Tragic Death)

    OpenAIRE

    A.G. Reznikov

    2016-01-01

    The article has been written in order to commemorate Canadian scientist Frederick Banting, the discoverer of insulin. There are briefly enlightened biography of the scientist and a history of insulin discovery. There is mentioned the role of scientist’s predecessors in decoding pathogenesis of diabetes and resolving the problem of development of therapeutic preparation of insulin.

  5. Frederick Banting and Insulin Discovery (75th Anniversary of Tragic Death

    Directory of Open Access Journals (Sweden)

    A.G. Reznikov

    2016-08-01

    Full Text Available The article has been written in order to commemorate Canadian scientist Frederick Banting, the discoverer of insulin. There are briefly enlightened biography of the scientist and a history of insulin discovery. There is mentioned the role of scientist’s predecessors in decoding pathogenesis of diabetes and resolving the problem of development of therapeutic preparation of insulin.

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

    International Nuclear Information System (INIS)

    Naidoo, C.

    1986-01-01

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

  7. Comparison of insulin signaling gene expression in insulin sensitive tissues between cats and dogs.

    Science.gov (United States)

    Mori, A; Lee, P; Takemitsu, H; Sako, T; Arai, T

    2009-03-01

    Diabetes mellitus (DM) is a common endocrine disease in cats and dogs with increasing prevalence. Type 1 DM appears to be the most common form of diabetes in dogs whereas Type 2 DM prevails for cats. Since insulin resistance is more frequently encountered in cats than dogs, our laboratory was interested in determining whether differences at the insulin signaling pathway level and differences in glucose and lipid metabolism could be observed between cats and dogs. Insulin resistance has been positively correlated to insulin signaling pathway abnormalities. As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85alpha mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. Different tissues were sampled because it is currently unknown where insulin-resistance arises from. In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. No distinct expression pattern emerged; however, differences were noted between canines and felines. In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85alpha mRNA expression levels which would predispose cats to develop insulin resistance. Moreover

  8. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    International Nuclear Information System (INIS)

    Duckworth, W.C.; Garcia, J.V.; Liepnieks, J.J.; Hamel, F.G.; Hermodson, M.A.; Frank, B.H.; Rosner, M.R.

    1989-01-01

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with 125 I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function

  9. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna; Söder, Olle; Johansson, Jan; Jörnvall, Hans

    2012-01-01

    Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  10. Beryllium and boron decoration form planar tetracoordinate carbon strips at the edge of BCN nanoribbons result in energy gap opposite variation and third-order nonlinear optical response improvement

    Science.gov (United States)

    Zhang, Minyi; Song, Jinshuai; Lu, Qianqian; Wei, Jing; Wu, Peng; Li, Chunsen

    2017-10-01

    Planar tetracoordinate carbon (ptC) with intriguing planar bond structure has triggered great attentions. In this work, B/Be-terminated decoration form armchair hybridized boron nitride and graphene nanoribbons with ptC structure (ptC-aBCNNRs) are investigated theoretically for third-order nonlinear optical (NLO) response by employing time-dependent density functional theory combined with sum-over-states method. Our calculations reveal Be and B decorated on ptC-aBCNNRs would result in opposite variation of energy gaps, and strongly enhance the NLO response in different third-order NLO processes. The strong third-order NLO response predicted for ptC-aBCNNRs is originated from the charge redistribution induced by ptC structure and hexagonal-BN ribbon insertion.

  11. Insulin regulation of (Na+, K+)-ATPase

    International Nuclear Information System (INIS)

    Lytton, J.

    1985-01-01

    This thesis describes an investigation into the mechanism of insulin stimulation of (Na + ,K + )=ATPase in rat adipocytes. Two molecular forms of the catalytic subunit of the enzyme were identified and denoted α and α(+), due to their similarity to those isozymes previously described from rat brain. Insulin specifically stimulated the α(+) form of the enzyme. The two forms of the enzyme had quite different affinities for intracellular sodium ion; insulin affected only the lower affinity of α(+), shifting it toward a higher value. However, the sodium affinity of (Na + ,K + )-ATPase activity in isolated membranes was equally high for both forms of the enzyme. This suggests that the difference in sodium affinity between the two forms observed in the cell is not inherent within the structure of the sodium pump, but must depend upon a selective interaction with another molecule which has been lost upon membrane isolation. Immunoprecipitation of both the catalytic subunits either from extracts of whole cells which had been labelled with [ 32 P] orthophosphate, or from membranes which had been labelled with γ-[ 32 P]ATP demonstrated that less than 1 in 100 molecules had a covalently bound phosphate insulin had no influence on this value. The amino terminal sequences of the first 4 amino acids of the catalytic subunits of both α (isolated from rat kidney) and α(+) (from rat brainstem axolemma) were determined. The result shows two highly homologous but clearly different molecules. It can thus be concluded that the insulin sensitive version of the enzyme is not derived from the common α form by a post-translational modification

  12. Continuous intraperitoneal insulin infusion in the treatment of type 1 diabetes mellitus: Glycaemia and beyond

    OpenAIRE

    van Dijk, Peter R.

    2015-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As compared to the most commonly used forms of insulin administration -injections and an externally placed pump- which deliver insulin in the subcutaneous (SC) tissue, CIPII delivers the insulin in the intraperitoneal space. CIPII using an implantable pump is an unique treatment which has been available for more than 30 year...

  13. 21 CFR 522.1160 - Insulin.

    Science.gov (United States)

    2010-04-01

    ... clinical signs in dogs with diabetes mellitus. (iii) Limitations. Federal law restricts this drug to use by... with diabetes mellitus. (iii) Limitations. Federal law restricts this drug to use by or on the order of... initiated if the duration of insulin action is determined to be inadequate. If twice-daily treatment is...

  14. Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent?

    Science.gov (United States)

    Cam, M C; Brownsey, R W; McNeill, J H

    2000-10-01

    The demonstration that the trace element vanadium has insulin-like properties in isolated cells and tissues and in vivo has generated considerable enthusiasm for its potential therapeutic value in human diabetes. However, the mechanisms by which vanadium induces its metabolic effects in vivo remain poorly understood, and whether vanadium directly mimics or rather enhances insulin effects is considered in this review. It is clear that vanadium treatment results in the correction of several diabetes-related abnormalities in carbohydrate and lipid metabolism, and in gene expression. However, many of these in vivo insulin-like effects can be ascribed to the reversal of defects that are secondary to hyperglycemia. The observations that the glucose-lowering effect of vanadium depends on the presence of endogenous insulin whereas metabolic homeostasis in control animals appears not to be affected, suggest that vanadium does not act completely independently in vivo, but augments tissue sensitivity to low levels of plasma insulin. Another crucial consideration is one of dose-dependency in that insulin-like effects of vanadium in isolated cells are often demonstrated at high concentrations that are not normally achieved by chronic treatment in vivo and may induce toxic side effects. In addition, vanadium appears to be selective for specific actions of insulin in some tissues while failing to influence others. As the intracellular active forms of vanadium are not precisely defined, the site(s) of action of vanadium in metabolic and signal transduction pathways is still unknown. In this review, we therefore examine the evidence for and against the concept that vanadium is truly an insulin-mimetic agent at low concentrations in vivo. In considering the effects of vanadium on carbohydrate and lipid metabolism, we conclude that vanadium acts not globally, but selectively and by enhancing, rather than by mimicking the effects of insulin in vivo.

  15. Insulin radioimmunoassay kit (125I) using polyethyleneglycol (PEG) and a double antibody separation method

    International Nuclear Information System (INIS)

    Borza, Virginia; Chariton, Delfina; Neacsu, Elena

    1997-01-01

    Insulin is a polypeptide hormone formed from proinsulin in the b-cells of the islets of Langerhans in the pancreas. It has a widespread effect on carbohydrate, lipid and protein metabolism. Diabetes mellitus is the result of an insulin deficiency brought about either by insufficient insulin secretion or by rapid insulin catabolism. The determination of the insulin level is important for differential etiologic diagnosis and subsequent therapy and prognosis. Insulin radioimmunoassay kit provides a sensitive, precise and specific assay for insulin concentration in serum. Standard and insulin in the patient sample compete with tracer for binding sites on an insulin antibody. The antigen-antibody combination, which forms during incubation time, will be separated from free insulin by different methods. The separation technique using the double antibody technique combined with Polyethyleneglycol (PEG) is presented. The results are compared with the separation method using PEG alone and with double antibody technique. Antiserum to insulin was produced in rats immunized with porcine insulin, while rabbits immunized with rat-g globulin were used as a source for the second antibody.The tested PEG was PEG 6000. The best results were obtained using the double antibody at a 1/50 dilution combined with 7.5 PEG solutions. The time for precipitating the antibody bound fraction by this technique was established to be 30 minutes. The results obtained using this method as separation technique for insulin - antibody complex were better than those obtained using the double antibody techniques or PEG as precipitating agent alone. (authors)

  16. Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

    International Nuclear Information System (INIS)

    Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

    1990-01-01

    In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

  17. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    levels are low. Physical activity is often difficult to carry out on a precise schedule and the exercise-induced changes in demand for insulin and calories vary according to the intensity and duration of exercise, time of day, and differ within and between individuals. Thus, physical training can...... is associated with less risk of metabolic derangement, and in genetically disposed individuals physical training may prevent development of overt diabetes possibly by diminishing the strain on the pancreatic beta cell. The latter, however, is only achieved if exercise is not accompanied by increased caloric......The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...

  18. Radioreceptor assay for insulin

    International Nuclear Information System (INIS)

    Suzuki, Kazuo

    1975-01-01

    Radioreceptor assay of insulin was discussed from the aspects of the measuring method, its merits and problems to be solved, and its clinical application. Rat liver 10 x g pellet was used as receptor site, and enzymatic degradation of insulin by the system contained in this fraction was inhibited by adding 1 mM p-CMB. 125 I-labelled porcine insulin was made by lactoperoxidase method under overnight incubation at 4 0 C and later purification by Sephadex G-25 column and Whatman CF-11 cellulose powder. Dog pancreatic vein serum insulin during and after the glucose load was determined by radioreceptor assay and radioimmunoassay resulting that both measurements accorded considerably. Radioreceptor assay would clarify the pathology of disorders of glucose metabolism including diabetes. (Tsukamoto, Y.)

  19. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... was not worsened in mice lacking functional a2AMPK in muscle. It is concluded that a2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased a2AMPK activity does...

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

    Science.gov (United States)

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

    2011-01-01

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

  1. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  2. Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans.

    Science.gov (United States)

    Liminet, Christelle; Vouillarmet, Julien; Chikh, Karim; Disse, Emmanuel

    2016-10-01

    We report the case of a patient with diabetes presenting a severe insulin-resistance syndrome due to the production of insulin autoantibodies by a lymphocytic lymphoma. We describe the various mechanisms leading to the production of insulin autoantibodies and insulin receptor autoantibodies and review the therapeutic possibilities. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  3. Changes In Insulin Resistance Risk Markers Among Oral ...

    African Journals Online (AJOL)

    However, observations at longer and abstinence periods should be made in order to generate sufficient data needed to establish convincing evidence among Nigerian users. Keywords: Insulin resistance, Oral contraceptives, Triacylglycerol, Lipids, Glucose. Egyptian Journal of Biochemistry and Molecular Biology Vol.

  4. Insulin Resistance: Causes And Metabolic Implications | Igharo ...

    African Journals Online (AJOL)

    Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin ...

  5. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  6. pH sensitive insulin-loaded nanohydrogel increases the effect of oral insulin in diabetic rats.

    Science.gov (United States)

    Karnoosh-Yamchi, Jalil; Rahmati-Yamchi, Mohammad; Akbarzadeh, Abolfazl; Davaran, Soodabeh; Ostad Rahimi, Ali Reza; Garnoosh, Khalil; Bahmani, Zahra; Ashoori, Mohammad; Mobasseri, Majid

    2017-09-01

    There are different methods for insulin administration in diabetic patient. Nano-hydrogel is one of the most talented drug carrier for its sensitivity to environmental stimulus. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction. The copolymers were characterized with Scanning electron microscopy (SEM) and Transient electron microscopy (TEM). Copolymers were loaded with regular insulin by modified double emulsion method. Diabetic rats are used for feeding insulin-loaded nanohydrogel. Analysis of the results from the measurement of the amount of blood insulin from the rats blood that received insulin in nanohydrogel loaded form compared with rats that received pure insulin is significantly high, which confirm that insulin has been able to pass from the stomach acid barrier by nanohydrogel and is absorbed from the intestine. Blood sugar levels from tested rats indicate that with increasing amount of insulin, blood sugar levels fall down. Our study confirms that insulin has been able to pass from the stomach acid barrier by nanohydrogel and be absorbed from the intestine.

  7. [The regulation of glucose-6-phosphate dehydrogenase and glycogen synthase activities by insulin superfamily peptides in myometrium of pregnant women and its impairments under different types of diabetes mellitus].

    Science.gov (United States)

    Kuznetsova, L A; Chistiakova, O V

    2009-01-01

    The regulatory effects of insulin, insulin-like growth factor 1 (IGF-1), and relaxin on glucose-6-phosphate dehydrogenase (G6PDH) and glycogen synthase (GS) activities have been studied in myometrium of pregnant women of control group and with diabetes mellitus of different etiology. In patients with type 1 diabetes G6PDH activity did not differ from the control group, but the enzyme activity was sharply decreased in pregnant women with type 2 diabetes and gestational diabetes. In the control group maximal stimulation of G6PDH activity was observed at 10(-9) M of peptides and their stimulating effect decreased in the following order: insulin > relaxin > IGF-1. In pregnant women with types 1 diabetes insulin effect on the enzyme activity was lower than in the control, and the effects of IGF-1 and relaxin were absent. In the group of pregnant women with type 2 diabetes and gestational diabetes the effects of insulin and IGF-1 were decreased, but the effect of relaxin was somewhat higher thus giving the following order in their efficiency relaxin > IGF-1 = insulin. At 10(-9) M peptides exhibited similar stimulating effects on the active form of GS-I, but had no influence on the total enzyme activity in the control group of pregnant women. In patients with type 1 diabetes GS activity remained unchanged (versus control), and peptides did not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in GS activity was accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational (treated and untreated) diabetes GS activity decreased, the effect of insulin was weaker, whereas the effects of relaxin and IGF-1 increased thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restored sensitivity of the enzymes to the peptide actions. At the same time, in women

  8. Modulation of insulin action by vanadate: evidence of a role for phosphotyrosine phosphatase activity to alter cellular signaling.

    Science.gov (United States)

    Fantus, I G; Deragon, G; Lai, R; Tang, S

    A number of vanadium compounds (vanadate, vanadyl sulfate, metavanadate) have insulin-mimicking actions both in vitro and in vivo. They have multiple biological effects in cultured cells and interact directly with various enzymes. The inhibitory action on phosphoprotein tyrosine phosphatases (PTPs) and enhancement of cellular tyrosine phosphorylation appear to be the most relevant to explain the ability to mimic insulin. We demonstrated that in rat adipocytes both acute insulin effects, e.g. stimulation of IGF-II and transferrin binding and a chronic effect, insulin receptor downregulation, were stimulated by vanadate. Vanadate also enhanced insulin binding, particularly at very low insulin concentrations, associated with increased receptor affinity. This resulted in increased adipocyte insulin sensitivity. Finally vanadate augmented the extent of activation of the insulin receptor kinase by submaximal insulin concentrations. This was associated with a prolongation of the insulin biological response, lipogenesis, after removal of hormone. in rat adipocytes vanadate promotes insulin action by three mechanisms, 1) a direct insulin-mimetic action, 2) an enhancement of insulin sensitivity and 3) a prolongation of insulin biological response. These data suggest that PTP inhibitors have potential as useful therapeutic agents in insulin-resistant and relatively insulin-deficient forms of diabetes mellitus.

  9. Insulin Therapy in Diabetic Hyperglycemic Emergencies

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez

    2014-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state are two of the most serious metabolic emergencies in diabetic patients. Objective: to identify the type of metabolic complications (diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state in order to analyze the patients’ outcome considering the plasma pH levels, as well as the mode of insulin administration. Method: a cross-sectional descriptive study was conducted in 52 patients admitted to the intensive care unit of the Enrique Cabrera Hospital from 2000 to 2007. The variables analyzed included: type of diabetes mellitus, type of acute complication, mode of insulin administration, blood gas analysis and outcome. Results: diabetic ketoacidosis occurred in 57.5 % of the type 1 diabetic patients and in the 42.5 % of the type 2 diabetics. None of the type 1 diabetics developed hyperglycemic hyperosmolar nonketotic state and this complication was observed in 23.0 % of the patients with diabetes type 2. Microdosing was the mode of insulin administration that predominated in both ketoacidosis and hyperglycemic state cases. Mortality was higher in the hyperglycemic state (67 % and using microdoses in the insulin therapy. Conclusions: diabetic ketoacidosis was the major complication. Mortality from diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state was high and the mode of insulin administration was inadequate in some patients.

  10. Depression and Insulin Resistance

    Science.gov (United States)

    Pearson, Sue; Schmidt, Mike; Patton, George; Dwyer, Terry; Blizzard, Leigh; Otahal, Petr; Venn, Alison

    2010-01-01

    OBJECTIVE To examine the association between depressive disorder and insulin resistance in a sample of young adults using the Composite International Diagnostic Interview to ascertain depression status. RESEARCH DESIGN AND METHODS Cross-sectional data were collected from 1,732 participants aged between 26 and 36 years. Insulin resistance was derived from blood chemistry measures of fasting insulin and glucose using the homeostasis model assessment method. Those identified with mild, moderate, or severe depression were classified as having depressive disorder. RESULTS The 12-month prevalence of depressive disorder was 5.4% among men and 11.7% among women. In unadjusted models mean insulin resistance was 17.2% (95% CI 0.7–36.0%, P = 0.04) higher in men and 11.4% (1.5–22.0%, P = 0.02) higher in women with depressive disorder. After adjustment for behavioral and dietary factors, the increased level of insulin resistance associated with depressive disorder was 13.2% (−3.1 to 32.3%, P = 0.12) in men and 6.1% (−4.1 to 17.4%, P = 0.25) in women. Waist circumference was identified as a mediator in the relationship between depression and insulin resistance, reducing the β coefficient in the fully adjusted models in men by 38% and in women by 42%. CONCLUSIONS A positive association was found between depressive disorder and insulin resistance in this population-based sample of young adult men and women. The association seemed to be mediated partially by waist circumference. PMID:20185745

  11. Heterogeneity of human plasma insulin: techniques for separating immunoreactive components and their determination by radioimmunoassay

    International Nuclear Information System (INIS)

    Souza, Iracelia Torres de Toledo e

    1977-01-01

    When human plasma is filtered on Sephadex G-SO fine, insulin immunoreactivity is recovered in two peaks: 'big insulin', the higher molecular weight component and 'little insulin', the lower molecular component, having elution volumes that correspond to those of porcine proinsulin 125 I and porcine insulin 125 I respectively. The presence of another form of immunoreactive insulin 'big big insulin' was detected from an insuloma suspect and its elution pattern corresponding to serum albumin. The eluates correspondent to 'big' and 'little' insulin as well as 'big big' component were assayed by radioimmunoassay using crystalline human insulin as a standard, porcine insulin 125 tracer and anti insulin serum. The antibody, raised in guinea-pigs, was sensitive and potent being adequate for the assay. The reactivity of insulin and proinsulin was tested against the antibody. The relative proportions of several components of total immunoreactive insulin in plasma were studied in basal conditions in five normal subjects and in the patient JSC with pancreatic insulin-secreting tumor as well as after glucose stimuli in all tolbutamide in JSC. (author)

  12. Insulin detemir versus insulin glargine for type 2 diabetes mellitus

    NARCIS (Netherlands)

    Swinnen, Sanne G.; Simon, Airin C. R.; Holleman, Frits; Hoekstra, Joost B.; DeVries, J. Hans

    2011-01-01

    Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but

  13. Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".

    Science.gov (United States)

    Kim, Tiffany Y; Woeber, Kenneth A; MacMaster, Heidimarie Windham; Rushakoff, Robert J

    2016-11-01

    We present the case of a 66-year-old woman who developed hypoglycemia following the prolonged infiltration of a high dose continuous peripheral IV insulin infusion. Case report. PubMed was searched for relevant literature on exogenous hyperinsulinemic hypoglycemia. The patient was postlung transplantation and was receiving high doses of glucocorticoids. Despite increasing the peripheral IV insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion line infiltrated, resulting in a large subcutaneous insulin depot, estimated to be 450 units of regular insulin. She subsequently experienced prolonged hypoglycemia that was managed with concentrated dextrose containing fluids. In our literature search, there were no similar case reports. The literature on insulin overdose, usually from suicide attempts, can help guide the management of iatrogenic hyperinsulinemic hypoglycemia. Important management considerations include anticipated duration of hypoglycemia, supplemental glucose, fluid management, and electrolyte monitoring. Peripheral IV insulin infusion infiltration should be considered when patients do not respond to increasing rates of insulin infusion.

  14. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  15. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  16. Localized modulated wave solutions in diffusive glucose–insulin systems

    Energy Technology Data Exchange (ETDEWEB)

    Mvogo, Alain, E-mail: mvogal_2009@yahoo.fr [Laboratory of Biophysics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon); Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Tambue, Antoine [The African Institute for Mathematical Sciences (AIMS) and Stellenbosch University, 6-8 Melrose Road, Muizenberg 7945 (South Africa); Center for Research in Computational and Applied Mechanics (CERECAM), and Department of Mathematics and Applied Mathematics, University of Cape Town, 7701 Rondebosch (South Africa); Ben-Bolie, Germain H. [Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Laboratory of Nuclear Physics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon); Kofané, Timoléon C. [Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Laboratory of Mechanics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon)

    2016-06-03

    We investigate intercellular insulin dynamics in an array of diffusively coupled pancreatic islet β-cells. The cells are connected via gap junction coupling, where nearest neighbor interactions are included. Through the multiple scale expansion in the semi-discrete approximation, we show that the insulin dynamics can be governed by the complex Ginzburg–Landau equation. The localized solutions of this equation are reported. The results suggest from the biophysical point of view that the insulin propagates in pancreatic islet β-cells using both temporal and spatial dimensions in the form of localized modulated waves. - Highlights: • The dynamics of an array of diffusively coupled pancreatic islet beta-cells is investigated. • Through the multiple scale expansion, we show that the insulin dynamics can be governed by the complex Ginzburg–Landau equation. • Localized modulated waves are obtained for the insulin dynamics.

  17. Periapical lesions decrease insulin signal and cause insulin resistance.

    Science.gov (United States)

    Astolphi, Rafael Dias; Curbete, Mariane Machado; Colombo, Natalia Helena; Shirakashi, Daisy Jaqueline; Chiba, Fernando Yamamoto; Prieto, Annelise Katrine Carrara; Cintra, Luciano Tavares Angelo; Bomfim, Suely Regina Mogami; Ervolino, Edilson; Sumida, Doris Hissako

    2013-05-01

    Inflammatory cytokines are associated with decreased insulin signal transduction. Moreover, local oral inflammation, such as that accompanying periodontal disease, is associated with insulin resistance and type 2 diabetes mellitus. The aim of this study was to evaluate the effect of periapical lesions (PLs) on insulin signaling and insulin sensitivity in rats. We hypothesized that PLs alter systemic insulin signaling and insulin sensitivity via elevated plasmatic tumor necrosis factor α (TNF-α). Wistar rats were divided into control (CN) and PL groups. PLs were induced by exposing pulpal tissue to the oral environment. After 30 days, insulin sensitivity was measured using the insulin tolerance test. After euthanization, maxillae were processed for histopathology. Plasmatic concentrations of tumor necrosis factor α (TNF-α) were determined via the enzyme-linked immunosorbent assay. Insulin signal transduction was evaluated using insulin receptor substrate tyrosine phosphorylation status and serine phosphorylation status in periepididymal white adipose tissue via Western blotting. For insulin signaling and insulin tolerance tests, the analyses performed were analysis of variance followed by the Tukey post hoc test. For TNF-α analysis, the Student's t test was used. In all tests, P change in serine phosphorylation status in white adipose tissue after insulin stimulation. PLs can cause alterations to both insulin signaling and insulin sensitivity, probably because of elevation of plasmatic TNF-α. The results from this study emphasize the importance of the prevention of local inflammatory diseases, such as PLs, with regard to the prevention of insulin resistance. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  18. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  19. Binding and degradation of 125I-insulin by renal glomeruli and tubules isolated from rats

    International Nuclear Information System (INIS)

    Meezan, E.; Freychet, P.; Nice Univ., 06

    1982-01-01

    Isolated rat renal glomeruli and tubules were shown to exhibit specific binding of 125 I-insulin and enzymatic degradation of the hormone. Binding to both renal fractions reached a plateau by 1 h at 22 0 C and increased linearly with increasing protein concentrations. Binding was inhibited in both preparations by insulin and its analogues in the order of relative potency: insulin > despentapeptide insulin > proinsulin, but insulin was ten times more potent in inhibiting 125 I-insulin binding to glomeruli than that to tubules, indicating a different affinity of receptors for the hormone in the two renal fractions (about 17 versus 210 μg unlabelled insulin/1 inhibiting 50% of the 125 I-insulin binding to glomeruli and tubules, respectively). Bound 125 I-insulin dissociated at a faster rate from tubules than from glomeruli; this release was accelreated by unlabelled insulin in both renal fractions, but to a greater extent in glomeruli than in tubules. Two-thirds of the total bound material released from glomeruli was found to be intact insulin as measured by trichloroacetic acid precipitation, whereas only one-third of the material released from tubules was intact. No direct relationship beteen binding and degradation of 125 I-insulin in these renal fractions could be demonstrated, however, because of the release of proteolytic enzymes into the incubation medium resulting in almost all degradation being extracellular. Although differing in their affinity for 125 I-insulin the high affinity glomerular insulin receptor and the lower affinity tubular insulin receptor have characteristics similar to those of insulin receptors in insulin responsive tissues. (orig.)

  20. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

    2014-01-01

    to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... variations in the PK are explained by variations in the subcutaneous blood flow. IAsp antibodies are found to be a large contributor to the variability of total insulin PK in a study by Chen et al. (2005), since only the free fraction is eliminated via the receptors. The contribution of these and other...... in subcutis, and blood flow dependent variations in absorption rate seem to dominate the PK variability of IAsp. It may be possible via e.g. formulation design to reduce some of these variability factors. (C) 2014 Elsevier B.V. All rights reserved....

  1. Treating non-insulin-dependent diabetes. Oral agents or insulin?

    OpenAIRE

    Shlossberg, A. H.

    1993-01-01

    This article describes suggested treatment regimens for non-insulin-dependent diabetes mellitus. Diet is usually the first-line therapy. If this fails, most patients should be given a trial of oral agents, usually sulfonylurea first. Sulfonylurea and metformin can be combined if necessary. If oral agents fail, insulin is indicated. Insulin and an oral agent sometimes are used together.

  2. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...

  3. Future of newer basal insulin

    OpenAIRE

    Madhu, S. V.; Velmurugan, M.

    2013-01-01

    Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins

  4. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  5. Chronic exercise increases insulin binding in muscles but not liver

    International Nuclear Information System (INIS)

    Bonen, A.; Clune, P.A.; Tan, M.H.

    1986-01-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver

  6. Chronic exercise increases insulin binding in muscles but not liver

    Energy Technology Data Exchange (ETDEWEB)

    Bonen, A.; Clune, P.A.; Tan, M.H.

    1986-08-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

  7. Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    2014-01-01

    Full Text Available Hyperglycemia (HG and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

  8. Insulin Resistance in Liver Diseases

    OpenAIRE

    Irshad, M

    2011-01-01

    Present report gives a brief and consolidated review of insulin resistance developed in chronic liver diseases. Insulin resistance remains an important feature of chronic liver diseases and progresses disease towards fibrogenesis. Of hepatitis viral infections, hepatitis C virus (HCV) was reported to have a significant role in inducing insulin resistance. Both viral particles as such, as well its structural components induce insulin resistance. Hepatitis C virus core protein, specially, cause...

  9. Insulin responses to administrations of amino acids and fatty acids in healthy cats.

    Science.gov (United States)

    Yasuda, Kyoji; Takashima, Satoshi; Takagi, Mitsuru; Nishii, Naohito; Ohba, Yasunori; Kitagawa, Hitoshi

    2011-10-01

    In order to compare the stimulation ability of insulin secretion, we determined changes in plasma glucose and insulin concentrations after intravenous administration of various amino acids and essential fatty acids in clinically healthy adult cats. Plasma glucose concentrations were within the normal ranges after injection of amino acids and fatty acids. Plasma insulin concentrations increased rapidly 2 to 4 min after injection of arginine, then decreased to the basal levels at 20 min in all five cats. Insulin peak responses were significantly greater in arginine injections than in normal saline (Pglucose (Pglucose toxication and required time for testing, the intravenous arginine tolerance test may be useful for estimation of insulin responses in cats.

  10. Kinetics of insulin disappearance from plasma in cortisone-treated normal subjects

    DEFF Research Database (Denmark)

    Ellemann, K; Thorsteinsson, B; Fugleberg, S

    1987-01-01

    The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1-5 mU/kg/min) was used to achieve...... infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered...

  11. Insulin Degludec (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin degludec must be used with another type of insulin (a short-acting insulin). In patients with type ... diabetes, insulin degludec may be used with another type of insulin or with oral medication(s) for diabetes. Insulin degludec ...

  12. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    ... diabetes, insulin glargine must be used with another type of insulin (a short-acting insulin). In people with type ... insulin glargine also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin glargine ...

  13. Insulin Detemir (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin detemir may be used with another type of insulin (a short-acting insulin). In patients with type ... insulin detemir also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin detemir ...

  14. 92 INSULIN RESISTANCE: CAUSES AND METABOLIC ...

    African Journals Online (AJOL)

    drclement

    2009-12-01

    Dec 1, 2009 ... ABSTRACT. Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle ...

  15. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

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

  16. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy ... Structure of porcine insulin. lized insulin. The use of chromatographic purification in the. 1970s reduced ... Heredity plays an important role in diabetes that shows up during old age. The stronger the family history,.

  17. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However ... PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene ... i.e. muscle, liver and fat, is extremely high (Brunetti et al 2001). However, there ...

  18. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    Insulin is a major protein hormone secreted by the p-cells of the pancreas and is important for the control of diabetes. Insulin is usually administered to diabetic patients through subcutaneous injection. This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy around the ...

  19. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    Diabetes is of two types. Type 1 or insulin-dependent diabetes mellitus (IDDM) is basically due to autoimmune- mediated destruction of the pancreatic β islets resulting in insulin deficiency. Patients with type 1 diabetes usually have to take exogenous insulin for survival and to prevent the development of ketoacidosis.

  20. UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

    Directory of Open Access Journals (Sweden)

    Manuel Correia

    Full Text Available In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2 excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes

  1. Polyethyleneglycol RIA (radioimmunoassay) insulin

    International Nuclear Information System (INIS)

    1988-01-01

    Insulin is a polypeptide hormone of M.W. 6,000 composed of two peptide chains, A and B, jointed by two cross-linked disulphide bonds and synthesized by the beta-cells of the islets of Langerhans of the pancreas. Insulin influences most of the metabolic functions of the body. Its best known action is to lower the blood glucose concentration by increasing the rate at which glucose is converted to glycogen in the liver and muscles and to fat in adipose tissue, by stimulating the rate of glucose metabolism and by depressing gluconeogenesis. Insulin stimulates the synthesis of proteins, DNA and RNA in cells generally, and promotes the uptake of aminoacids and their incorporation into muscle protein. It increases the uptake of glucose in adipose tissue and its conversion into fat and inhibits lipolysis. Insulin primary action is on the cell membrane, where it probably facilitates the transport of glucose and aminoacids into the cells. At the same time it may activate intracellular enzymes such as glycogen synthetase, concerned with glycogen synthesis. (Author) [es

  2. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  3. Radioimmunoassay test system for detection of anti-insulin antibodies

    International Nuclear Information System (INIS)

    Dudko, N.V.; Piven', N.V.; Ibragimova, G.V.; Kasatkin, Yu.N.

    1995-01-01

    A radiodiagnostic test system has been developed and commercial kit for radioimmunoassay of anti-insulin antibodies in human blood serum created. Clinical trials of the kit in patients (150 diabetics with types 1 and 2 condition) and normal subjects (n=100) demonstrated the possibility of using this kit for the detection of preclinical forms of diabetes and for distinguishing groups at risk of diabetes among children and adults, for the detection of insulin resistance, for the differential diagnosis of diabetes, and for monitoring the efficacy of insulin therapy. 9 refs.; 1 tab

  4. Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion.

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available Recent studies have identified unique brain effects of insulin detemir (Levemir®. Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation.In mice, we examined insulin detemir's prolonged brain exposure by continuous subcutaneous (s.c. application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings.Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total, suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001 and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters.The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens.

  5. Insulin Resistance and Hypogonadism

    Directory of Open Access Journals (Sweden)

    Shahana Shermin

    2013-05-01

    Full Text Available Backgound: The number of hypogonads is increasing day by day. It may be due to sedentary life style with increased obesity, increased tension or stressed lifestyle among all groups of populations. Visceral obesity is associated with insulin resistance, diabetes mellitus and also with hypogonadism.Objective: This study was carried out to determine the proportion of insulin resistance among male subjects with hypogonadism in different age groups along with status of erectile quality among diabetics and non diabetics.Materials and method: This cross sectional study among 161 adult male subjects aged ≥ 20 to ≤ 60 years were purposively selected from Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM, Dhaka, Bangladesh between May 2009 to September 2010. Glycemic status and insulin resistance (by HOMA-R were done and relevant history were documented.Results: The highest proportion (38.9% of hypogonadism was in ≥ 50 years age group whereas highest proportion (39.6% of the eugonads was in the age group of 40 to 49 years. More than half of the hypogonad subjects had weak erectile quality (54.0% which were followed by absent erectile quality in 32.7% and 13.3% subjects had normal erectile quality. Among the eugonad subjects 41.7% had normal erectile quality, 41.6% subjects had weak erectile quality and 16.7% subjects had no erectile quality. More than ninety percent of the hypogonad subjects and about 60% of the eugonad subjects had insulin resistance. The average HOMA-R was more in the subjects with hypogonadism with diabetes which was highly significant (p-value < 0.001.Conclusion: Hypogonadism is associated with insulin resistance.

  6. Vanadium compounds as insulin mimics.

    Science.gov (United States)

    Orvig, C; Thompson, K H; Battell, M; McNeill, J H

    1995-01-01

    That vanadium compounds act in an insulin-mimetic fashion both in vitro and in vivo has been well established. Both inorganic and organic vanadium compounds have been shown to lower plasma glucose levels, increase peripheral glucose uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize liver enzyme activities in a variety of animal models of both type I and type II diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of action and potentiation of vanadium's insulin-mimetic effect by appropriate ligand binding would seem to be the highest priorities for future investigation.

  7. Pivotal role of leptin in insulin effects

    Directory of Open Access Journals (Sweden)

    R.B. Ceddia

    1998-06-01

    Full Text Available The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

  8. Insulin Signalling: The Inside Story.

    Science.gov (United States)

    Posner, Barry I

    2017-02-01

    Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  9. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

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

    2015-01-01

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

  10. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

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

  11. Insulin analog with additional disulfide bond has increased stability and preserved activity

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Ribel, Ulla

    2013-01-01

    under high physical stress even though the C-terminus of the B-chain thought to be directly involved in fibril formation was not modified. Importantly, this analog was capable of forming hexamer upon Zn addition as typical for wild-type insulin and its crystal structure showed only minor deviations from...... (HI) structure. This insulin analog had increased affinity for the insulin receptor and apparently augmented glucodynamic potency in a normal rat model compared with HI. Addition of the disulfide bond also resulted in a 34.6°C increase in melting temperature and prevented insulin fibril formation...... bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. To address this hypothesis, we designed insulin with an additional interchain disulfide bond in positions A10/B4 based on Cα-Cα distances, solvent exposure, and side-chain orientation in human insulin...

  12. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  13. Calcul des efforts de deuxième ordre à très haute fréquence sur des plates-formes à lignes tendues Computing High-Frequency Second Order Loads on Tension Leg Platforms

    Directory of Open Access Journals (Sweden)

    Chen X.

    2006-11-01

    Full Text Available Le problème considéré ici est celui de l'évaluation des efforts excitateurs de deuxième ordre (en mode somme, c'est-à-dire prenant place aux sommes deux à deux des fréquences de houle sur des plates-formes à lignes tendues. Ces efforts sont tenus pour responsables de comportements résonnants (en roulis, tangage et pilonnement observés lors d'essais en bassin et pourraient réduire sensiblement la durée de vie en fatigue des tendons. Des résultats sont tout d'abord présentés pour une structure simplifiée, consistant en 4 cylindres verticaux reposant sur le fond marin. L'intérêt de cette géométrie est que tous les calculs peuvent être menés à terme de façon quasi analytique. Les résultats obtenus permettent d'illustrer le haut degré d'interaction entre les colonnes, et la faible décroissance du potentiel de diffraction de deuxième ordre avec la profondeur. On présente ensuite des résultats pour une plate-forme réelle, celle de Snorre. Tension Leg Platforms (TLP's are now regarded as a promising technology for the development of deep offshore fields. As the water depth increases however, their natural periods of heave, roll and pitch tend to increase as well (roughly to the one-half power, and it is not clear yet what the maximum permissible values for these natural periods can be. For the Snorre TLP for instance, they are only about 2. 5 seconds, which seems to be sufficiently low since there is very limited free wave energy at such periods. Model tests, however, have shown some resonant response in sea states with peak periods of about 5 seconds. Often referred to as springing , this resonant motion can severely affect the fatigue life of tethers and increase their design loads. In order to calculate this springing motion at the design stage, it is necessary to identify and evaluate both the exciting loads and the mechanisms of energy dissipation. With the help of the French Norwegian Foundation a joint effort was

  14. Word Order

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2015-01-01

    The way constituents are ordered in a linguistic expression is determined by general principles and language specific rules. This article is mostly concerned with general ordering principles and the three main linguistic categories that are relevant for constituent order research: formal, functio...

  15. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-01-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125 I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125 I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125 I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  16. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  17. Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

    Science.gov (United States)

    Mady, Mohsen M.; Elshemey, Wael M.

    2011-06-01

    Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

  18. A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin

    DEFF Research Database (Denmark)

    Hansen, L; Hansen, T; Vestergaard, H

    1995-01-01

    The regulatory G-subunit of the glycogen-associated form of protein phosphatase 1 (PP1) plays a crucial part in muscle tissue glycogen synthesis and breakdown. As impaired insulin stimulated glycogen synthesis in peripheral tissues is considered to be a pathogenic factor in subsets of non-insulin...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Klaassen, J.K.

    1986-01-01

    Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of (/sup 125/I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred.

  1. Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Klaassen, J.K.

    1986-01-01

    Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of ( 125 I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred

  2. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor subs...

  3. Topical insulin accelerates cutaneous wound healing in insulin-resistant diabetic rats

    OpenAIRE

    Yu, Tianyi; Gao, Min; Yang, Peilang; Pei, Qing; Liu, Dan; Wang, Di; Zhang, Xiong; Liu, Yan

    2017-01-01

    Insulin signaling defects could lead to insulin resistance in insulin target organs: typically, in the muscler, liver, and adipose tissue. We have observed that insulin accelerated diabetic wound healing in our previous works; to further elucidate the mechanism, we investigated the expression and activation of insulin and insulin-like growth factor (IGF)-1 signaling, compared insulin sensitivity in skin tissue with that in liver tissue, and also observed the regulation of insulin on inflammat...

  4. Insulin, IGF-1 and longevity

    OpenAIRE

    van Heemst, Diana

    2010-01-01

    It has been demonstrated in invertebrate species that the evolutionarily conserved insulin and insulin-like growth factor (IGF) signaling (IIS) pathway plays a major role in the control of longevity. In the roundworm Caenorhabditis elegans, single mutations that diminish insulin/IGF-1 signaling can increase lifespan more than twofold and cause the animal to remain active and youthful much longer than normal. Likewise, substantial increases in lifespan are associated with mutations that reduce...

  5. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  6. Insulin, glucagon, and liver regeneration

    International Nuclear Information System (INIS)

    Kirsch, R.E.; Frith, L.O'C.; Vinik, A.; Terblanche, J.

    1980-01-01

    Partially hepatectomized rats receiving intragastric amino acids synthesize less DNA than similar rats receiving intragastric water alone. In the present study insulin and glucagon levels were measured in rats receiving amino acids or water alone. In both groups of rats insulin levels were depressed and glucagon levels elevated. These findings suggest that insulin and glucagon do not play a major role in the regulation of liver regeneration after partial hepatectomy in the rat

  7. Laser surface treatment on a nickel based alloy in order to form chromium oxide to reduce cations release in primary circuit. Experimental and numerical study of laser mater interaction

    International Nuclear Information System (INIS)

    Gouton, Lucille

    2015-01-01

    Alloy 690 (60%Ni, 30%Cr, 10%Fe) is mainly used in primary circuit pipes for nuclear power plants.The aim of this thesis is to form a Cr 2 O 3 layer, using laser surface melting, with the objective of creating a chromium-rich oxide layer. In order to optimize the treatment, it was first important to determine parameters influence on the layer oxide properties then, with the objective of a deeper understanding of mechanisms involved, to address thermo-physical phenomena occurring during and after the laser pulse striking the upper surface. A deep parametric study first enabled to find an optimized laser surface treatment which produces chromium enrichment of the upper surface and a dense and continuous oxide layer. This treatment has been applied on samples, set in a primary medium simulation loop. Experiments and calculations were carried out to provide understanding of surface chromium enrichment by laser process. The results were shown to explain chromium enrichment until melt pool solidification occurred on the upper surface, assumingly just before chromium oxide formation. This was also promoted by a high affinity with oxygen and a higher stability of Cr 2 O 3 oxide compared with other potential oxide formation. (author) [fr

  8. A geometry preserving, conservative, mesh-to-mesh isogeometric interpolation algorithm for spatial adaptivity of the multigroup, second-order even-parity form of the neutron transport equation

    Science.gov (United States)

    Welch, J. A.; Kópházi, J.; Owens, A. R.; Eaton, M. D.

    2017-10-01

    In this paper a method is presented for the application of energy-dependent spatial meshes applied to the multigroup, second-order, even-parity form of the neutron transport equation using Isogeometric Analysis (IGA). The computation of the inter-group regenerative source terms is based on conservative interpolation by Galerkin projection. The use of Non-Uniform Rational B-splines (NURBS) from the original computer-aided design (CAD) model allows for efficient implementation and calculation of the spatial projection operations while avoiding the complications of matching different geometric approximations faced by traditional finite element methods (FEM). The rate-of-convergence was verified using the method of manufactured solutions (MMS) and found to preserve the theoretical rates when interpolating between spatial meshes of different refinements. The scheme's numerical efficiency was then studied using a series of two-energy group pincell test cases where a significant saving in the number of degrees-of-freedom can be found if the energy group with a complex variation in the solution is refined more than an energy group with a simpler solution function. Finally, the method was applied to a heterogeneous, seven-group reactor pincell where the spatial meshes for each energy group were adaptively selected for refinement. It was observed that by refining selected energy groups a reduction in the total number of degrees-of-freedom for the same total L2 error can be obtained.

  9. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

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

  10. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  11. Insulin resistance and cancer: the role of insulin and IGFs.

    Science.gov (United States)

    Djiogue, Sefirin; Nwabo Kamdje, Armel Hervé; Vecchio, Lorella; Kipanyula, Maulilio John; Farahna, Mohammed; Aldebasi, Yousef; Seke Etet, Paul Faustin

    2013-02-01

    Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

  12. Intensive Insulin Therapy: Tight Blood Sugar Control

    Science.gov (United States)

    Intensive insulin therapy: Tight blood sugar control Intensive insulin therapy can help prevent long-term diabetes complications. Consider the ... cases if you have type 2 diabetes — intensive insulin therapy may be the key to long-term ...

  13. The evolutionary benefit of insulin resistance

    NARCIS (Netherlands)

    Soeters, Maarten R.; Soeters, Peter B.

    2012-01-01

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

  14. Challenges constraining access to insulin in the private-sector market of Delhi, India.

    Science.gov (United States)

    Sharma, Abhishek; Kaplan, Warren A

    2016-01-01

    India's majority of patients-including those living with diabetes-seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition.

  15. Challenges constraining access to insulin in the private-sector market of Delhi, India

    Science.gov (United States)

    Kaplan, Warren A

    2016-01-01

    Objective India's majority of patients—including those living with diabetes—seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. Methods A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. Results In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. Conclusions The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition. PMID:28588966

  16. INSULIN HORMONE EFFECTS ON FT&ST MUSCLES OF BODY BULDING ATHLETS AND DIABETIC PEOPLE TYPE

    Directory of Open Access Journals (Sweden)

    MEHDI GHORBANI

    2014-07-01

    Full Text Available Insulin is a Hormone that is secreted from pancreas and has an undeniable role in regulating blood - suger. In medicine, the injection samples of this Hormone are used for controlling diabetes disease. But recently, it has been used by athletes for driving G lucose and Amino Acids in to muscle - cells in industrial and injection forms for fast development of muscle volume and power among potency athletes specially body - builders. The present study, is reviewing consumption consequences of this drug by athletes and it’s important and of course hidden hazards. In this study, the Hormone’s impression and it’s high secretion and mechanism imbalance in body - builders bodies are analyzed by following Dosage and period of Insulin consumption among athletes and body - b uilders and studying different forms and injection amounts of Insulin, and comparing them with diabetes disease. Results show that Insulin is a Hormone with high Anabolic effect and it is responsible for nutrient materials transmission into blood stream an d muscle - cells. The blood - suger is saved as glycogen in muscles on this hormone effect and Amino acid transmission is developed in body’s muscle system. This features by muscle manufacturing apparent of athletes and muscle exhausting delay in fast contra cting muscle fibers and enthusiasm of practicing for hours, dosen’t cause to ignore the dangerous disadvantageous of this hormone including: imbalance of metabolism such as extra lipid burning and glycogen saving in body. Because of Insulin long consumptio n body produces little amount of glycogen and adrenaline hormones to re increase the amount of blood - suger, therefore increasing blood - suger isn’t declared with warning signals such as: trembling and nervousness, and athletes encounter with the shock of decreasing blood - suger (Hyper - glysemia and die. This study shows that in correct consumption of diabetes drugs are hazardous in body. Builders in different

  17. Insulin resistance and muscle insulin receptor substrate‐1 serine hyperphosphorylation

    Science.gov (United States)

    Stuart, Charles A.; Howell, Mary E. A.; Cartwright, Brian M.; McCurry, Melanie P.; Lee, Michelle L.; Ramsey, Michael W.; Stone, Michael H.

    2014-01-01

    Abstract Insulin resistance in metabolic syndrome subjects is profound in spite of muscle insulin receptor and insulin‐responsive glucose transporter (GLUT4) expression being nearly normal. Insulin receptor tyrosine kinase phosphorylation of insulin receptor substrate‐1 (IRS‐1) at Tyr896 is a necessary step in insulin stimulation of translocation of GLUT4 to the cell surface. Serine phosphorylation of IRS‐1 by some kinases diminishes insulin action in mice. We evaluated the phosphorylation status of muscle IRS‐1 in 33 subjects with the metabolic syndrome and seventeen lean controls. Each underwent euglycemic insulin clamps and a thigh muscle biopsy before and after 8 weeks of either strength or endurance training. Muscle IRS‐1 phosphorylation at six sites was quantified by immunoblots. Metabolic syndrome muscle IRS‐1 had excess phosphorylation at Ser337 and Ser636 but not at Ser307, Ser789, or Ser1101. Ser337 is a target for phosphorylation by glycogen synthase kinase 3 (GSK3) and Ser636 is phosphorylated by c‐Jun N‐terminal kinase 1 (JNK1). Exercise training without weight loss did not change the IRS‐1 serine phosphorylation. These data suggest that baseline hyperphosphorylation of at least two key serines within muscle IRS‐1 diminishes the transmission of the insulin signal and thereby decreases the insulin‐stimulated translocation of GLUT4. Excess fasting phosphorylation of muscle IRS‐1 at Ser636 may be a major cause of the insulin resistance seen in obesity and might prevent improvement in insulin responsiveness when exercise training is not accompanied by weight loss. PMID:25472611

  18. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  19. The cardiovascular effects of insulin.

    Science.gov (United States)

    Younk, Lisa M; Lamos, Elizabeth M; Davis, Stephen N

    2014-07-01

    Cardiovascular disease remains one of the leading causes of morbidity and mortality in diabetes mellitus. A causal link between insulin, atherosclerosis and cardiovascular risk has been investigated at the basic science level and studied in large clinical trials. The cardiovascular actions of insulin and its role at the level of the endothelium will be reviewed. Cardiovascular outcomes in several large diabetes trials where insulin management was prominent will be summarized. The vascular actions of insulin are complex and mediated primarily via nitric oxide and endothelin-1. It appears that insulin resistance, rather than hyperinsulinemia itself, increases cardiovascular risk. In fact, hyperinsulinemia in the setting of normal beta cell function protects obese and insulin-resistant individuals from type 2 diabetes. Large clinical trials have supported that insulin management is not associated with increased adverse outcomes. A multifactorial approach targeting modifiable risk factors, including smoking cessation, blood pressure and lipid management, reduces cardiovascular risk. Therapy goals should be individualized and hypoglycemia, especially in individuals receiving insulin management, should be strictly avoided.

  20. Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells.

    NARCIS (Netherlands)

    Freund, C.M.A.H.; Ward-van Oostwaard, D.; Monshouwer-Kloots, J.; van den Brink, S.; van Rooijen, M.A.; Xu, X.; Zweigerdt, R.; Mummery, C.L.; Passier, R.

    2008-01-01

    Human embryonic stem cells (hESC) can proliferate indefinitely while retaining the capacity to form derivatives of all three germ layers. We have reported previously that hESC differentiate into cardiomyocytes when cocultured with a visceral endoderm-like cell line (END-2). Insulin/insulin-like

  1. Continuous intraperitoneal insulin infusion in the treatment of type 1 diabetes mellitus : Glycaemia and beyond

    NARCIS (Netherlands)

    van Dijk, Peter R.

    2015-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As compared to the most commonly used forms of insulin administration -injections and an externally placed pump- which deliver

  2. Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

    DEFF Research Database (Denmark)

    O'Harte, F P; Boyd, A C; McKillop, A M

    2000-01-01

    Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M(r) 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly(1) and Phe(1) of the insulin A- and B-...

  3. Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B

    2006-01-01

    The influence of ligand binding and conformation state on the thermostability of hexameric zinc-insulin was studied by differential scanning calorimetry (DSC). The insulin hexamer exists in equilibrium between the forms T6, T3R3, and R6. Phenolic ligands induce and stabilize the T3R3- and R6-stat...

  4. Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes

    Science.gov (United States)

    McNay, Ewan C.; Recknagel, Andrew K.

    2011-01-01

    Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cogntive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients. PMID:21907815

  5. Stability of Asp(B28) Insulin Exposed to Modified and Unmodified Polypropylene

    DEFF Research Database (Denmark)

    Fristrup, C. J.; Jankova, K.; Eskimergen, R.

    2015-01-01

    Polypropylene (PP) plates have been modified with two different hydrophilic polymeric materials, poly(N,N-dimethylacrylamide) (poly(DMAAm)) and poly(poly(ethylene glycol)methacrylate) (poly(PEGMA)) in order to reduce insulin adsorption when the plates were exposed to insulin aspart (Asp(B28...

  6. Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes.

    Science.gov (United States)

    Gutiérrez, Tomás; Parra, Valentina; Troncoso, Rodrigo; Pennanen, Christian; Contreras-Ferrat, Ariel; Vasquez-Trincado, César; Morales, Pablo E; Lopez-Crisosto, Camila; Sotomayor-Flores, Cristian; Chiong, Mario; Rothermel, Beverly A; Lavandero, Sergio

    2014-11-07

    Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca(2+) release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood. In the present study we investigated insulin-dependent mitochondrial Ca(2+) signaling in normal and norepinephrine or insulin like growth factor-1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca(2+)-fluorescent probes we showed that insulin increases mitochondrial Ca(2+) levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca(2+) uniporter, as well as by siRNA-dependent mitochondrial Ca(2+) uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor-1-stimulated cells. This resulted in a reduction in mitochondrial Ca(2+) uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca(2+) uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling. Mitochondrial Ca(2+) uptake is a key event in insulin signaling and metabolism in cardiomyocytes.

  7. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    Sakai, Yukio

    1979-01-01

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  8. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  9. Degludec: the new ultra-long insulin analogue.

    Science.gov (United States)

    Tambascia, Marcos Antonio; Eliaschewitz, Freddy Goldberg

    2015-01-01

    The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

  10. TRPM5 regulates glucose-stimulated insulin secretion.

    Science.gov (United States)

    Brixel, Lili R; Monteilh-Zoller, Mahealani K; Ingenbrandt, Claudia S; Fleig, Andrea; Penner, Reinhold; Enklaar, Thorsten; Zabel, Bernhard U; Prawitt, Dirk

    2010-06-01

    Insulin secretion in beta-pancreatic cells due to glucose stimulation requires the coordinated alteration of cellular ion concentrations and a substantial membrane depolarization to enable insulin vesicle fusion with the cellular membrane. The cornerstones of this cascade are well characterized, yet current knowledge argues for the involvement of additional ion channels in this process. TRPM5 is a cation channel expressed in beta-cells and proposed to be involved in coupling intracellular Ca(2+) release to electrical activity and cellular responses. Here, we report that TRPM5 acts as an indispensable regulator of insulin secretion. In vivo glucose tolerance tests showed that Trpm5 (-/-) -mice maintain elevated blood glucose levels for over an hour compared to wild-type littermates, while insulin sensitivity is normal in Trpm5 (-/-) -mice. In pancreatic islets isolated from Trpm5 (-/-) -mice, hyperglycemia as well as arginine-induced insulin secretion was diminished. The presented results describe a major role for TRPM5 in glucose-induced insulin secretion beyond membrane depolarization. Dysfunction of the TRPM5 protein could therefore be an important factor in the etiology of some forms of type 2 diabetes, where disruption of the normal pattern of secretion is observed.

  11. [Insulin and diabetes control in Argentina].

    Science.gov (United States)

    Gagliardino, Juan J; Costa Gil, José E; Faingold, María C; Litwak, León; Fuente, Graciela V

    2013-01-01

    As in the rest of the world, there is a significant gap between scientific knowledge regarding diabetes mellitus and the daily practice outcome, in Argentina. Inadequate diabetes control combined with associated cardiovascular risk factors are responsible for an elevated morbid-mortality incidence and the consequent raise in the socioeconomic burden. Some of the factors leading to this situation are the late diagnosis of the disease, the clinical "inertia" (reluctance to prescribe insulin) and the poor education given to the health care team as well as the persons with diabetes. The implementation of a national diabetologic education program targeting health care providers, the persons with diabetes and their families, could contribute to optimize the appropriate insulin prescription, and consequently improve their life quality, while reducing the disease socioeconomic burden. In order to optimize the education program's strategy outcome, insulinization cabinets should be incorporated, the participation of all health systems (public health, social security and private health insurance companies), the media, health sciences, schools and the pharmaceutical industry are needed.

  12. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  13. Transnational Normative Orders

    DEFF Research Database (Denmark)

    Kjaer, Poul F.

    2013-01-01

    by a protracted dual movement where the expansion and densification of statehood and autonomous forms of transnational ordering gradually emerged in a mutually constitutive fashion. One implication of this is that neither the concept of the state nor the concept of nonstate transnational entities is adequately...... of the law of normative orders has been introduced, specifying them as respectively oriented towards establishing internal condensation of a given normative order and external compatibility between different normative orders. With this background, a framework for the analysis of constitutional frameworks...

  14. Transnational Normative Orders

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    2017-01-01

    by a protracted dual movement where the expansion and densification of statehood and autonomous forms of transnational ordering gradually emerged in a mutually constitutive fashion. One implication of this is that neither the concept of the state nor the concept of nonstate transnational entities is adequately...... of the law of normative orders has been introduced, specifying them as respectively oriented towards establishing internal condensation of a given normative order and external compatibility between different normative orders. With this background, a framework for the analysis of constitutional frameworks...

  15. SHIP2: a "new" insulin pathway target for aging research.

    Science.gov (United States)

    Accardi, Giulia; Virruso, Claudia; Balistreri, Carmela Rita; Emanuele, Fabrizio; Licastro, Federico; Monastero, Roberto; Porcellini, Elisa; Vasto, Sonya; Verga, Salvatore; Caruso, Calogero; Candore, Giuseppina

    2014-04-01

    Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some single-nucleotide polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patients with metabolic syndrome and some related conditions, we decided to conduct a case-control study on this gene, analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest a putative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather than age-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway with aging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging might depend on its effect on the insulin/IGF-1 pathway.

  16. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

  17. Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus

    International Nuclear Information System (INIS)

    Trischitta, V.; Benzi, L.; Brunetti, A.; Cecchetti, P.; Marchetti, P.; Vigneri, R.; Navalesi, R.

    1987-01-01

    We studied total cell-associated A14-[ 125 I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity. Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[ 125 I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[ 125 I]insulin, [ 125 I]iodide, or [ 125 I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients

  18. Developing a Commercial Air Ultrasonic Ceramic Transducer to Transdermal Insulin Delivery

    Science.gov (United States)

    Jabbari, Nasrollah; Asghari, Mohammad Hossein; Ahmadian, Hassan; Mikaili, Peyman

    2015-01-01

    The application of low-frequency ultrasound for transdermal delivery of insulin is of particular public interest due to the increasing problem of diabetes. The purpose of this research was to develop an air ultrasonic ceramic transducer for transdermal insulin delivery and evaluate the possibility of applying a new portable and low-cost device for transdermal insulin delivery. Twenty-four rats were divided into four groups with six rats in each group: one control group and three experimental groups. Control group (C) did not receive any ultrasound exposure or insulin (untreated group). The second group (T1) was treated with subcutaneous insulin (Humulin® R, rDNA U-100, Eli Lilly and Co., Indianapolis, IN) injection (0.25 U/Kg). The third group (T2) topically received insulin, and the fourth group (T3) received insulin with ultrasound waves. All the rats were anesthetized by intraperitoneal injection of ketamin hydrochloride and xylazine hydrochloride. Blood samples were collected after anesthesia to obtain a baseline glucose level. Additional blood samples were taken every 15 min in the whole 90 min experiment. In order for comparison the changes in blood glucose levels” to “ In order to compare the changes in blood glucose levels. The statistical multiple comparison (two-sided Tukey) test showed a significant difference between transdermal insulin delivery group (T2) and subcutaneous insulin injection group (T1) during 90 min experiment (P = 0.018). In addition, the difference between transdermal insulin delivery group (T2) and ultrasonic transdermal insulin delivery group (T3) was significant (P = 0.001). Results of this study demonstrated that the produced low-frequency ultrasound from this device enhanced the transdermal delivery of insulin across hairless rat skin. PMID:26120571

  19. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

    International Nuclear Information System (INIS)

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jiráček, Jiří; Brzozowski, Andrzej M.

    2014-01-01

    [AsnB26]- and [GlyB26]-insulin mutants attain a B26-turn like fold without assistance of chemical modifications. Their structures match the insulin receptor interface and expand the spectrum of insulin conformations. The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms

  20. Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle

    DEFF Research Database (Denmark)

    D'Hulst, Gommaar; Sylow, Lykke; Hespel, Peter

    2015-01-01

    PURPOSE: To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans. METHODS: Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min ...... insulin intolerance developed independently of defects in conventional insulin signaling in skeletal muscle....

  1. Aperiodic order

    CERN Document Server

    Grimm, Uwe

    2017-01-01

    Quasicrystals are non-periodic solids that were discovered in 1982 by Dan Shechtman, Nobel Prize Laureate in Chemistry 2011. The mathematics that underlies this discovery or that proceeded from it, known as the theory of Aperiodic Order, is the subject of this comprehensive multi-volume series. This second volume begins to develop the theory in more depth. A collection of leading experts, among them Robert V. Moody, cover various aspects of crystallography, generalising appropriately from the classical case to the setting of aperiodically ordered structures. A strong focus is placed upon almost periodicity, a central concept of crystallography that captures the coherent repetition of local motifs or patterns, and its close links to Fourier analysis. The book opens with a foreword by Jeffrey C. Lagarias on the wider mathematical perspective and closes with an epilogue on the emergence of quasicrystals, written by Peter Kramer, one of the founders of the field.

  2. Fibrillization kinetics of insulin solution in an interfacial shearing flow

    Science.gov (United States)

    Balaraj, Vignesh; McBride, Samantha; Hirsa, Amir; Lopez, Juan

    2015-11-01

    Although the association of fibril plaques with neurodegenerative diseases like Alzheimer's and Parkinson's is well established, in-depth understanding of the roles played by various physical factors in seeding and growth of fibrils is far from well known. Of the numerous factors affecting this complex phenomenon, the effect of fluid flow and shear at interfaces is paramount as it is ubiquitous and the most varying factor in vivo. Many amyloidogenic proteins have been found to denature upon contact at hydrophobic interfaces due to the self-assembling nature of protein in its monomeric state. Here, fibrillization kinetics of insulin solution is studied in an interfacial shearing flow. The transient surface rheological response of the insulin solution to the flow and its effect on the bulk fibrillization process has been quantified. Minute differences in hydrophobic characteristics between two variants of insulin- Human recombinant and Bovine insulin are found to result in very different responses. Results presented will be in the form of fibrillization assays, images of fibril plaques formed, and changes in surface rheological properties of the insulin solution. The interfacial velocity field, measured from images (via Brewster Angle Microscopy), is compared with computations. Supported by NNX13AQ22G, National Aeronautics and Space Administration.

  3. Delineation of atypical insulin receptors from classical insulin and type I insulin-like growth factor receptors in human placenta.

    OpenAIRE

    Jonas, H A; Cox, A J; Harrison, L C

    1989-01-01

    Insulin-like growth factor (IGF)-binding sites copurifying with human placental insulin receptors during insulin-affinity chromatography consist of two immunologically distinct populations. One reacts with monoclonal antibody alpha IR-3, but not with antibodies to the insulin receptor, and represents Type I IGF receptors; the other reacts only with antibodies to the insulin receptor and is precipitated with a polyclonal receptor antibody (B-10) after labelling with 125I-multiplication-stimula...

  4. Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report

    OpenAIRE

    Taboada, Giselle F; de Freitas, Marta S; da S Corr?a, Fernanda H; Junior, Carlos RMA; de B Gomes, Mar?lia

    2009-01-01

    Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value:

  5. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    Swinnen, S. G.; Dain, M.-P.; Mauricio, D.; DeVries, J. H.; Hoekstra, J. B.; Holleman, F.

    2010-01-01

    We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2

  6. Structural Perspectives of Insulin Receptor Isoform-Selective Insulin Analogs

    Czech Academy of Sciences Publication Activity Database

    Jiráček, Jiří; Žáková, Lenka

    2017-01-01

    Roč. 8, Jul 27 (2017), č. článku 167. ISSN 1664-2392 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 Keywords : insulin receptor * insulin binding * analog * diabetes * glucose Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.675, year: 2016 http://journal.frontiersin.org/article/10.3389/fendo.2017.00167/full

  7. Insulin vials vs. insulin cartridges: Further cost considerations.

    Science.gov (United States)

    Al-Sharayri, Mohammad G; Alsabrah, Tariq M; Aljbori, Tareq M; Abu-Rumman, Ala'a Eddeen K

    2013-04-01

    Many studies have provided evidence that favor the use of insulin pens over traditional insulin vials due to lower overall costs. The cost of insulin in the Royal Medical Services in Jordan is subject to other considerations due to the favorable tender prices and the process of dispensing of insulin within the Royal Medical Services. To highlight further cost considerations associated with the wastage in the use of insulin vials and cartridges in the Jordanian Royal Medical Services. Two random samples were selected from prescriptions dispensed for diabetic patients using insulin in January 2012 from the outpatient pharmacy in Al-Hussein Hospital, King Hussein Medical Center, Amman, Jordan. First sample was selected from prescriptions of patients using vials; second sample was selected from prescriptions of patients using pens and cartridges. Average costs for insulin and wastage were calculated per patient from the Royal Medical Services perspective. The average direct cost per patient using vials was JD 5.197 and for those using cartridges was JD 22.135. The average wasted quantity per patient in the first sample was more than ten times that of the second sample. The cost of the average wasted quantity per patient in the first sample (1.022 JD) was more than the double that in the second sample (0.441 JD). Although, the direct cost of insulin per patient by using vials was lower than cartridges, there was a substantial reduction in the cost of wastage by using the cartridges in the Jordanian Royal Medical Services outpatients.

  8. Order Quantity Distributions in Make-to-Order Manufacturing

    DEFF Research Database (Denmark)

    Eriksen, Poul Svante; Nielsen, Peter

    2011-01-01

    This paper presents both an analytical and a numerical investigation into the order quantities received by a company in the form of customer orders. A discussion of assumptions regarding the behavior of demand in the form of customer orders from various perspectives within manufacturing planning...... and control with a special emphasis on the make-to-order environment is presented. A methodological framework for analyzing the behavior of orders and investigate the validity of the assumptions is given. Furthermore, an analytical approach to identify the horizon needed for aggregating orders to achieve...

  9. The Need for Faster Insulin: Problem Solved?

    OpenAIRE

    Muchmore, Douglas B.

    2016-01-01

    Considerable progress in treatment of diabetes has been made in the nearly 100 years following the discovery of insulin, and advances in insulin therapy have improved convenience, quality of life, overall glycemic control (A1C), and risk of hypoglycemia. An unmet need remains for a mealtime insulin that can faithfully reproduce the metabolic profile that ensues following meal ingestion in healthy persons. A number of “ultra-fast” insulin programs have been initiated, and Afrezza® (insulin hum...

  10. Bioavailability and variability of biphasic insulin mixtures

    DEFF Research Database (Denmark)

    Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik

    2012-01-01

    Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble insulin and insulin suspensions in a recent contribution to this journal (Søeborg et al., 2009). In the present article, the absorp...... mixtures. The results can be used in both the development of novel insulin products and in the planning of the treatment of insulin dependent diabetic patients....

  11. Cardiovascular effects of basal insulins.

    Science.gov (United States)

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence.

  12. Insulin therapy in special conditions

    Directory of Open Access Journals (Sweden)

    León E Litwak

    2017-10-01

    Full Text Available Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

  13. Modular forms

    NARCIS (Netherlands)

    Edixhoven, B.; van der Geer, G.; Moonen, B.; Edixhoven, B.; van der Geer, G.; Moonen, B.

    2008-01-01

    Modular forms are functions with an enormous amount of symmetry that play a central role in number theory, connecting it with analysis and geometry. They have played a prominent role in mathematics since the 19th century and their study continues to flourish today. Modular forms formed the

  14. Role of AMPK in Regulating Muscle Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus

    obtained during this PhD support a role of AMPK in regulating muscle insulin sensitivity, which may occur through phosphorylation of the downstream target TBC1D4. We find that prior AICAR treatment (pharmacological AMPK activator) and in situ contraction enhance mouse muscle insulin sensitivity in an AMPK...... prevail in healthy lean subjects. In the present thesis, experimental results from the three studies as well as unpublished observations are placed in the context of existing literature in order to provide a general overview of the current understandings within this field of research....

  15. Eccentric exercise decreases maximal insulin action in humans

    DEFF Research Database (Denmark)

    Asp, Svend; Daugaard, J R; Kristiansen, S

    1996-01-01

    subjects participated in two euglycaemic clamps, performed in random order. One clamp was preceded 2 days earlier by one-legged eccentric exercise (post-eccentric exercise clamp (PEC)) and one was without the prior exercise (control clamp (CC)). 2. During PEC the maximal insulin-stimulated glucose uptake...... over the eccentric thigh was marginally lower when compared with the control thigh, (11.9%, 64.6 +/- 10.3 vs. 73.3 +/- 10.2 mumol kg-1 min-1, P = 0.08), whereas no inter-thigh difference was observed at a submaximal insulin concentration. The glycogen concentration was lower in the eccentric thigh...

  16. Purification, characterization, and biological activity of insulins from the spotted dogfish, Scyliorhinus canicula, and the hammerhead shark, Sphyrna lewini.

    Science.gov (United States)

    Anderson, W Gary; Ali, Mohamed F; Einarsdóttir, Ingibjörg E; Schäffer, Lauge; Hazon, Neil; Conlon, J Michael

    2002-03-01

    Insulin was purified from pancreatic extracts of two elasmobranch species belonging to different families in the order Carcharhiniformes, the European spotted dogfish, Scyliorhinus canicula (Scyliorhinidae), and the hammerhead shark, Sphyrna lewini (Carcharhinidae). The amino acid sequence of dogfish insulin was established as A-chain GIVDHCCRNT(10)CSLYDLEGYC(20)NQ and B-chain LPSQHLCGSH(10)LVETLYFVCG(20)QKGFYYVPKV(30). The primary structure of hammerhead shark insulin was similar to that of dogfish insulin with only 2 amino acid substitutions at A8 (R --> H) and B30 (V --> I). The elasmobranch insulins were markedly different from human insulin (17 amino acid substitutions) but all the residues in human insulin that are believed to be important in determining the receptor binding conformation (B6, B8, B11, B13, B23, B24, B25, A2, A3, and A19) have been conserved in the elasmobranch insulins with the exception of the conservative substitution Phe --> Tyr at B25. Consistent with this, dogfish and human insulin showed almost identical binding affinity to the recombinant solubilized human insulin receptor (K(D) values of 14.0 and 18.6 pM, respectively; relative potency 133%). Previous studies have shown that bovine insulin produces severe and sustained hypoglycemia in elasmobranchs but the effect is of slow onset. Bolus arterial injections of dogfish insulin (10 nmol x kg(-1)) into unanesthetized, fasting dogfish (n = 9) produced no changes in blood glucose, 3-hydroxybutyrate, and acetoacetate concentrations over a 4-h period. In a second series of experiments (n = 7), dogfish insulin (10 nmol x kg(-1)) produced a significant (P < 0.05) fall in blood glucose after 12 h that persisted for at least 48 h, but no change in ketone body concentrations. The data indicate that the metabolic actions of an endogenous elasmobranch insulin in an elasmobranch are similar to those previously described for mammalian insulin.

  17. Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes.

    Science.gov (United States)

    Liu, Ying; Liu, Fei; Grundke-Iqbal, Inge; Iqbal, Khalid; Gong, Cheng-Xin

    2011-09-01

    Brain glucose metabolism is impaired in Alzheimer's disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin-PI3K-AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM-AD and seven control cases. We found decreases in the levels and activities of several components of the insulin-PI3K-AKT signalling pathway in AD and T2DM cases. The deficiency of insulin-PI3K-AKT signalling was more severe in individuals with both T2DM and AD (T2DM-AD). This decrease in insulin-PI3K-AKT signalling could lead to activation of glycogen synthase kinase-3β, the major tau kinase. The levels and the activation of the insulin-PI3K-AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O-GlcNAcylation, suggesting that impaired insulin-PI3K-AKT signalling might contribute to neurodegeneration in AD through down-regulation of O-GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin-PI3K-AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over-activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer's disease. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Design of a selective insulin receptor tyrosine kinase inhibitor and its effect on glucose uptake and metabolism in intact cells

    Energy Technology Data Exchange (ETDEWEB)

    Saperstein, R.; Vicario, P.P.; Strout, H.V.; Brady, E.; Slater, E.E.; Greenlee, W.J.; Onedyka, D.L.; Patchett, A.A.; Hangauer, D.G. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA))

    1989-06-27

    An inhibitor of the insulin receptor tyrosine kinase (IRTK), (hydroxy-2-napthalenylmethyl)phosphonic acid, was designed and synthesized and was shown to be an inhibitor of the biological effects of insulin in vitro. With a wheat germ purified human placental insulin receptor preparation, this compound inhibited the insulin-stimulated autophosphorylation of the 95-kDa {beta}-subunit of the insulin receptor. The ability of the kinase to phosphorylate an exogenous peptide substrate, angiotensin II, was also inhibited. Half-maximal inhibition of basal and insulin-stimulated human placental IRTK activity was found at concentrations of 150 and 100 {mu}M, respectively, with 2 mM angiotensin II as the peptide substrate. The inhibitor was found to be specific for tyrosine kinases over serine kinases and noncompetitive with ATP. The inhibitor was converted into various (acyloxy)methyl prodrugs in order to achieve permeability through cell membranes. These prodrugs inhibited insulin-stimulated autophosphorylation of the insulin receptor 95-kDa {beta}-subunit in intact CHO cells transfected with human insulin receptor. Inhibition of insulin-stimulated glucose oxidation in isolated rat adipocytes and 2-deoxyglucose uptake into CHO cells was observed with these prodrugs. The data provide additional evidence for the involvement of the insulin receptor tyrosine kinase in the regulation of glucose uptake and metabolism. These results and additional data reported herein suggest that this class of prodrugs and inhibitors will be useful for modulating the activity of a variety of tyrosine kinases.

  19. Insulin fibrillation: The influence and coordination of Zn2+

    DEFF Research Database (Denmark)

    Frankær, Christian Grundahl; Sønderby, Pernille; Bang, Maria Blanner

    2017-01-01

    Protein amyloid fibrillation is obtaining much focus because it is connected with amyloid-related human diseases such as Alzheimer's disease, diabetes mellitus type 2, or Parkinson's disease. The influence of metal ions on the fibrillation process and whether it is implemented in the amyloid...... Electron Microscopy and Thioflavin T fluorescence measurements. It is well-known that Zn2+ ions coordinate and stabilize the hexameric forms of insulin. However, this study is the first to show that zinc indeed binds to the insulin fibrils. Furthermore, zinc influences the kinetics and the morphology...... of the fibrils. It also shows that zinc coordinates to histidine residues in an environment, which is similar to the coordination seen in the insulin R6 hexamers, where three histidine residues and a chloride ion is coordinating the zinc....

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  1. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  2. Acute insulin resistance mediated by advanced glycation endproducts in severely burned rats.

    Science.gov (United States)

    Zhang, Xing; Xu, Jie; Cai, Xiaoqing; Ji, Lele; Li, Jia; Cao, Bing; Li, Jun; Hu, Dahai; Li, Yan; Wang, Haichang; Xiong, Lize; Xiao, Ruiping; Gao, Feng

    2014-06-01

    Hyperglycemia often occurs in severe burns; however, the underlying mechanisms and importance of managing postburn hyperglycemia are not well recognized. This study was designed to investigate the dynamic changes of postburn hyperglycemia and the underlying mechanisms and to evaluate whether early glycemic control is beneficial in severe burns. Prospective, randomized experimental study. Animal research laboratory. Sprague-Dawley rats. Anesthetized rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive vehicle, insulin, and a soluble form of receptor for advanced glycation endproducts treatments. An in vitro study was performed on cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment. We found that blood glucose change presented a distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour postburn, respectively. Acute insulin resistance evidenced by impaired insulin signaling and glucose uptake occurred at 3-hour postburn, which was associated with the second hyperglycemia and positively correlated with mortality. Mechanistically, we found that serum carboxymethyllysine, a dominant species of advanced glycation endproducts, increased within 1-hour postburn, preceding the occurrence of insulin resistance. More importantly, treatment of animals with soluble form of receptor for advanced glycation endproducts, blockade of advanced glycation endproducts signaling, alleviated severe burn-induced insulin resistance. In addition, early hyperglycemic control with insulin not only reduced serum carboxymethyllysine but also blunted postburn insulin resistance and reduced mortality. These findings suggest that severe burn-induced insulin resistance is partly at least mediated by serum advanced glycation endproducts and positively correlated with mortality. Early glycemic control with insulin or inhibition of advanced glycation endproducts with soluble form of receptor

  3. Mastering HTML5 forms

    CERN Document Server

    Gupta, Gaurav

    2013-01-01

    This tutorial will show you how to create stylish forms, not only visually appealing, but interactive and customized, in order to gather valuable user inputs and information.Enhance your skills in building responsive and dynamic web forms using HTML5, CSS3, and related technologies. All you need is a basic understanding of HTML and PHP.

  4. Novel nanoparticles for oral insulin delivery via the paracellular pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Y-H [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China); Chen, C-T [Division of Biotechnology and Pharmaceutical Research, National Health Research Institute, Zhunan Town, Miaoli County, Taiwan (China); Liang, H-F [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China); Kulkarni, Anandrao R [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China); Lee, P-W [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China); Chen, C-H [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China); Sung, H-W [Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan (China)

    2007-03-14

    Novel nanoparticles (NPs) coated with chitosan which allow insulin to be administered orally were developed. The NPs could transiently and reversibly open the tight junctions in Caco-2 cell monolayers, thus increasing their paracellular permeability. After oral administration of the FITC-labelled NPs, fluorescence signals, co-localized with ZO-1 proteins, were observed at cell-cell contact sites in the small intestine of rats. The intensity of fluorescence signals observed at the duodenum was stronger and appeared at a deeper level than at the jejunum and the ileum. The insulin-loaded NPs suspended in water were stable in typical storage conditions. Release of the loaded insulin depended greatly on the stability of the NPs at distinct pH environments. Oral administration of insulin in the form of NPs in diabetic rats demonstrated a sustained effect of decreasing the blood glucose level over at least 10 h, indicating the effect of the prepared NPs in enhancing the absorption of fully functional insulin.

  5. Optimizing insulin pump therapy: a quality improvement project.

    Science.gov (United States)

    Meade, Lisa T; Rushton, Wanda E

    2013-01-01

    The purpose of the study was to assess insulin pump use and provide ongoing education. A quality improvement project using a pump assessment questionnaire was implemented at an endocrinology office in the southeastern United States. The questionnaire was designed to evaluate all aspects of insulin pump therapy, including pump operations, infusion set failure, management of acute complications, and usage of advanced device features. Eighty-nine patients (80% with type 1 diabetes and 20% with type 2 diabetes) completed the questionnaire at the endocrinology practice. A certified diabetes educator reviewed the questions with each patient, identifying deficiencies and training opportunities. The most common areas of deficiency identified after implementation of the assessment form included the following: expired or no basal insulin prescription in the event of pump failure or removal, no mupirocin (Bactroban®, GlaxoSmithKline, Research Triangle Park, North Carolina) prescription for suspected site infections, lack of insulin syringe if pump stopped working, failure to check urine ketones, no antiemetic prescription for sick day intervention, using manual bolus instead of bolus calculator, and lack of in-date glucagon kit. Use of a pump assessment questionnaire allows for focused discussion concerning patient behaviors related to pump operations, troubleshooting, and self-management. Incorporating use of a pump assessment questionnaire into routine practice may result in improved patient education and avoidance of adverse events specific to insulin pump therapy.

  6. EFFECT OF ORAL INSULIN IN BLOOP G1UCOSE CONCENTRATION

    Directory of Open Access Journals (Sweden)

    DJ. FARID

    1993-07-01

    Full Text Available Gastrointestinal tract can not be used as a route for oral administration of polypeptid hormones because"nof their enzymatic degradation."nDegradation of these macromoleculcs in acidic and alkaline conditions determines the need for using"nprotective delivery systems."nIn this research microcmulsions were used for protection of insulin against proteolytic enzymesof"ngastrointestinal tract. Cholestrol and phospholipids of egg yolk have been used as lipid phase as lipid phase"nand Lecithin as surfactant."nInsulin Regular was used as aqueous phase, being entrapped with lipidic phase in W/O manner. Male"nrabbits with body weight of about 1-1.5 KG were accomplished and oral insulin was force fed to them."nBlood collection has been carried out from heart every 15 minutes after oral administration."nReduction in blood glucose level indicates the well being protection of insulin and absorbtion of it through"nepithelium of small intestine. Increasing of glucose level in placebo demonstrates that endogenous"ninsulin has not been responsible for serum glucose reduction."nThis experiment suggests that microemulsions formed with egg Yolk compounds have the ability to be an"nalternate for parenteral administration of insulin and other chemicals sensitive to enzymatic degradation, in"nhuman.

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

    Science.gov (United States)

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

    2016-04-01

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

  8. Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Hansen, Torben; Bjørbaek, C; Vestergaard, H

    1993-01-01

    Due to alternative splicing of exon 11 of the receptor gene, the human insulin receptor exists in two forms, that have distinct tissue-specific expression and are functionally different. Needle biopsies obtained from vastus lateralis muscle from 20 patients with noninsulin-dependent diabetes...... mellitus (NIDDM) and 20 normal control subjects were analyzed for the relative expression of insulin receptor mRNA variants in a novel assay using fluorescence-labeled primers and subsequent analysis on an automated DNA sequencer. In subgroups of patients and control subjects, insulin binding and tyrosine...

  9. Analysis of the nonlinear dynamic behavior of power systems using normal forms of superior order; Analisis del comportamiento dinamico no lineal de sistemas de potencia usando formas normales de orden superior

    Energy Technology Data Exchange (ETDEWEB)

    Marinez Carrillo, Irma

    2003-08-01

    This thesis investigates the application of parameter disturbance methods of analysis to the nonlinear dynamic systems theory, for the study of the stability of small signal of electric power systems. The work is centered in the determination of two fundamental aspects of interest in the study of the nonlinear dynamic behavior of the system: the characterization and quantification of the nonlinear interaction degree between the fundamental ways of oscillation of the system and the study of the ways with greater influence in the response of the system in the presence of small disturbances. With these objectives, a general mathematical model, based on the application of the expansion in series of power of the nonlinear model of the power system and the theory of normal forms of vector fields is proposed for the study of the dynamic behavior of the power system. The proposed tool generalizes the existing methods in the literature to consider effects of superior order in the dynamic model of the power system. Starting off of this representation, a methodology is proposed to obtain analytical solutions of loop back and the extension of the existing methods is investigated to identify and quantify the of interaction degree among the fundamental ways of oscillation of the system. The developed tool allows, from analytical expressions of loop backs, the development of analytical measures to evaluate the stress degree in the system, the interaction between the fundamental ways of oscillation and the determination of stability borders. The conceptual development of the proposed method in this thesis offers, on the other hand, a great flexibility to incorporate detailed models of the power system and the evaluation of diverse measures of the nonlinear modal interaction. Finally, the results are presented of the application of the method of analysis proposed for the study of the nonlinear dynamic behavior in a machine-infinite bus system considering different modeled degrees

  10. Insulin and insulin-like growth factor receptors and responses

    International Nuclear Information System (INIS)

    Roth, R.A.; Steele-Perkins, G.; Hari, J.; Stover, C.; Pierce, S.; Turner, J.; Edman, J.C.; Rutter, W.J.

    1988-01-01

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  11. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low...

  12. Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle.

    Science.gov (United States)

    Franko, A; von Kleist-Retzow, J C; Böse, M; Sanchez-Lasheras, C; Brodesser, S; Krut, O; Kunz, W S; Wiedermann, D; Hoehn, M; Stöhr, O; Moll, L; Freude, S; Krone, W; Schubert, M; Wiesner, R J

    2012-10-01

    The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1α expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors.

  13. Insulin Analogs Applied with Continuous Subcutaneous Insulin Infusion (Pump in the Treatment of Diabetes

    Directory of Open Access Journals (Sweden)

    Ercan Tuncel

    2015-03-01

    Full Text Available Diabetes mellitus (DM is an important health problem that should be treated efficiently because of its high prevalence and high morbidity and mortality due to its complications. In patients with DM, the application of a treatment which provides physiologic insulin secretion as such in healthy individuals is directly related with the prevention of diabetes complications. Insulin analogs, which were developed in recent years and shown to have pharmacokinetic and pharmacodynamic superiority to human insulin, have made it possible to obtain natural insulin pattern in the body. In addition to development of insulin analogs, introduction of insulin application method of “continuous subcutaneous insulin infusion” (insulin pump has led a new era in the treatment of DM. In this review, treatment of type 1 and 2 DM patients with insulin analogs, particularly insulin aspart, applied with insulin pump was discussed in the light of the current literature.

  14. Clinical use of the co-formulation of insulin degludec and insulin aspart

    DEFF Research Database (Denmark)

    Kumar, A; Awata, T; Bain, S C

    2016-01-01

    AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage...... as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting...... (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...

  15. Improving the estimation of mealtime insulin dose in adults with type 1 diabetes: the Normal Insulin Demand for Dose Adjustment (NIDDA) study.

    Science.gov (United States)

    Bao, Jiansong; Gilbertson, Heather R; Gray, Robyn; Munns, Diane; Howard, Gabrielle; Petocz, Peter; Colagiuri, Stephen; Brand-Miller, Jennie C

    2011-10-01

    Although carbohydrate counting is routine practice in type 1 diabetes, hyperglycemic episodes are common. A food insulin index (FII) has been developed and validated for predicting the normal insulin demand generated by mixed meals in healthy adults. We sought to compare a novel algorithm on the basis of the FII for estimating mealtime insulin dose with carbohydrate counting in adults with type 1 diabetes. A total of 28 patients using insulin pump therapy consumed two different breakfast meals of equal energy, glycemic index, fiber, and calculated insulin demand (both FII = 60) but approximately twofold difference in carbohydrate content, in random order on three consecutive mornings. On one occasion, a carbohydrate-counting algorithm was applied to meal A (75 g carbohydrate) for determining bolus insulin dose. On the other two occasions, carbohydrate counting (about half the insulin dose as meal A) and the FII algorithm (same dose as meal A) were applied to meal B (41 g carbohydrate). A real-time continuous glucose monitor was used to assess 3-h postprandial glycemia. Compared with carbohydrate counting, the FII algorithm significantly decreased glucose incremental area under the curve over 3 h (-52%, P = 0.013) and peak glucose excursion (-41%, P = 0.01) and improved the percentage of time within the normal blood glucose range (4-10 mmol/L) (31%, P = 0.001). There was no significant difference in the occurrence of hypoglycemia. An insulin algorithm based on physiological insulin demand evoked by foods in healthy subjects may be a useful tool for estimating mealtime insulin dose in patients with type 1 diabetes.

  16. Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system.

    Science.gov (United States)

    Paul, Pijush Kumar; Treetong, Alongkot; Suedee, Roongnapa

    2017-06-27

    In this study, we investigate molecularly imprinted polymers (MIPs), which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

  17. Disulfide bridges remain intact while native insulin converts into amyloid fibrils.

    Directory of Open Access Journals (Sweden)

    Dmitry Kurouski

    Full Text Available Amyloid fibrils are β-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. Understanding the structural organization of amyloid fibrils can be beneficial for the search of drugs to successfully treat diseases associated with protein misfolding. The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman (DUVRR and Nuclear Magnetic Resonance (NMR spectroscopy combined with hydrogen-deuterium exchange. The compositions of the fibril core and unordered parts were determined at single amino acid residue resolution. All three disulfide bonds of native insulin remained intact during the aggregation process, withstanding scrambling. Three out of four tyrosine residues were packed into the fibril core, and another aromatic amino acid, phenylalanine, was located in the unordered parts of insulin fibrils. In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin.

  18. Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

    Directory of Open Access Journals (Sweden)

    Paul Pijush Kumar

    2017-06-01

    Full Text Available In this study, we investigate molecularly imprinted polymers (MIPs, which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

  19. Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

    DEFF Research Database (Denmark)

    O'Harte, F P; Boyd, A C; McKillop, A M

    2000-01-01

    Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M(r) 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly(1) and Phe(1) of the insulin A- and B-......(-7) mol/liter) was 22-38% less effective (P abdominal muscle.......-chains, respectively. Intraperitoneal (i.p.) administration of diglycated insulin to mice alone or in combination with glucose (7 nmol/kg) resulted in a 43-61% and 11-34% reduction in glucose lowering activity, respectively, compared with native insulin. Consistent with these findings, diglycated insulin (10(-9) to 10...

  20. An Immunomodulatory Device Improves Insulin Resistance in Obese Porcine Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Angela J. Westover

    2016-01-01

    Full Text Available Obesity is associated with tissue inflammation which is a crucial etiology of insulin resistance. This inflammation centers around circulating monocytes which form proinflammatory adipose tissue macrophages (ATM. Specific approaches targeting monocytes/ATM may improve insulin resistance without the adverse side effects of generalized immunosuppression. In this regard, a biomimetic membrane leukocyte processing device, called the selective cytopheretic device (SCD, was evaluated in an Ossabaw miniature swine model of insulin resistance with metabolic syndrome. Treatment with the SCD in this porcine model demonstrated a decline in circulating neutrophil activation parameters and monocyte counts. These changes were associated with improvements in insulin resistance as determined with intravenous glucose tolerance testing. These improvements were also reflected in lowering of homeostatic model assessment- (HOMA- insulin resistant (IR scores for up to 2 weeks after SCD therapy. These results allow for the planning of first-in-man studies in obese type 2 diabetic patients.

  1. Switching basal insulins in type 2 diabetes: practical recommendations for health care providers.

    Science.gov (United States)

    Anderson, Sarah L; Trujillo, Jennifer M; Anderson, John E; Tanenberg, Robert J

    2017-12-27

    Basal insulin remains the mainstay of treatment of type 2 diabetes when diet changes and exercise in combination with oral drugs and other injectable agents are not sufficient to control hyperglycemia. Insulin therapy should be individualized, and several factors influence the choice of basal insulin; these include pharmacological properties, patient preferences, and lifestyle, as well as health insurance plan formularies. The recent availability of basal insulin formulations with longer durations of action has provided further dosing flexibility; however, patients may need to switch agents throughout therapy for a variety of personal, clinical, or economic reasons. Although a unit-to-unit switching approach is usually recommended, this conversion strategy may not be appropriate for all patients and types of insulin. Glycemic control and risk of hypoglycemia must be closely monitored by health care providers during the switching process. In addition, individual changes in care and formulary coverage need to be adequately addressed in order to enable a smooth transition with optimal outcomes.

  2. Chronic inflammation, insulin resistance, psoriasis - which have in common?

    Directory of Open Access Journals (Sweden)

    M. S. Rasin

    2016-01-01

    Full Text Available Psoriasis is recognized as system immune inflammatory disease at a certain genetic basis. It was found that psoriasis develops under the influence of chronic systemic inflammation low intensity (low grade inflammation that induced insulin resistance, and is one of the clinical forms of the Immune Metabolic Disease (IMD, along with atherosclerosis, hypertension, type 2 diabetes, obesity and many other diseases, whose tight relationship with psoriasis are installed. Knowledge of the etiology, pathogenesis and molecular mechanisms of communication with other clinical forms of the IMD opens up new ways of prevention and treatment of psoriasis. Please note that other diseases associated with psoriasis, occurring hidden, often have greater predictive value for the life and health of the patient than mild or moderate forms of psoriasis, and be not limited to ascertaining the diagnosis and symptomatic treatment and actively participate in prevention. Debated question of the application of funds, suppressing systemic inflammation and insulin resistance in the treatment of psoriasis.

  3. Characterization of the chicken muscle insulin receptor

    International Nuclear Information System (INIS)

    Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

    1987-01-01

    Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

  4. Cloning and characterisation of Schistosoma japonicum insulin receptors.

    Directory of Open Access Journals (Sweden)

    Hong You

    2010-03-01

    Full Text Available Schistosomes depend for growth and development on host hormonal signals, which may include the insulin signalling pathway. We cloned and assessed the function of two insulin receptors from Schistosoma japonicum in order to shed light on their role in schistosome biology.We isolated, from S. japonicum, insulin receptors 1 (SjIR-1 and 2 (SjIR-2 sharing close sequence identity to their S. mansoni homologues (SmIR-1 and SmIR-2. SjIR-1 is located on the tegument basal membrane and the internal epithelium of adult worms, whereas SjIR-2 is located in the parenchyma of males and the vitelline tissue of females. Phylogenetic analysis showed that SjIR-2 and SmIR-2 are close to Echinococcus multilocularis insulin receptor (EmIR, suggesting that SjIR-2, SmIR-2 and EmIR share similar roles in growth and development in the three taxa. Structure homology modelling recovered the conserved structure between the SjIRs and Homo sapiens IR (HIR implying a common predicted binding mechanism in the ligand domain and the same downstream signal transduction processing in the tyrosine kinase domain as in HIR. Two-hybrid analysis was used to confirm that the ligand domains of SjIR-1 and SjIR-2 contain the insulin binding site. Incubation of adult worms in vitro, both with a specific insulin receptor inhibitor and anti-SjIRs antibodies, resulted in a significant decrease in worm glucose levels, suggesting again the same function for SjIRs in regulating glucose uptake as described for mammalian cells.Adult worms of S. japonicum possess insulin receptors that can specifically bind to insulin, indicating that the parasite can utilize host insulin for development and growth by sharing the same pathway as mammalian cells in regulating glucose uptake. A complete understanding of the role of SjIRs in the biology of S. japonicum may result in their use as new targets for drug and vaccine development against schistosomiasis.

  5. Genetics Home Reference: type A insulin resistance syndrome

    Science.gov (United States)

    ... Conditions Type A insulin resistance syndrome Type A insulin resistance syndrome Printable PDF Open All Close All Enable ... as energy. In people with type A insulin resistance syndrome , insulin resistance impairs blood sugar regulation and ultimately leads ...

  6. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes

    DEFF Research Database (Denmark)

    Rodbard, H W; Cariou, B; Zinman, B

    2013-01-01

    The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes.......The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes....

  7. Impact of insulin pump on quality of life of diabetic patients.

    Science.gov (United States)

    Ghazanfar, Haider; Rizvi, Syed Wajih; Khurram, Aliya; Orooj, Fizza; Qaiser, Iman

    2016-01-01

    Diabetes is an emerging health problem, both in developing and developed countries and has an enormous economic and social impact. The objective of our study was to find the impact of insulin pump on the quality of life of patients with type 2 diabetes (T2D) and compare it to the quality of life of patients with T2D using an insulin pen. This is a case-control study which was conducted among patients with T2D presenting between November 2014 and November 2015. A total of 83 patients with T2D, using insulin pump were enrolled in the study as cases and 322 patients with T2D not using insulin pump but using insulin pens were enrolled as controls. Short form-36 quality of life questionnaire was used for data collection. Mean age of patients using insulin pump was 52.49 ± 9.28 while the mean age of patients not using insulin pump was 54.72 ± 16.87. Mean score of all domains in the questionnaire was found to be higher in patients using insulin pump as compared to patients not using insulin pumps (P insulin pump decreased the frequency of hypoglycemic episodes. Insulin pump has significantly improved the quality of life of patients in terms of better self-esteem, decreased stress, and better mood. It has resulted in improved physical health, meal time flexibility, and ease of travel. It allows patient to have more active participation in social and recreational activities improving their personal and family life.

  8. Impact of insulin pump on quality of life of diabetic patients

    Directory of Open Access Journals (Sweden)

    Haider Ghazanfar

    2016-01-01

    Full Text Available Aim: Diabetes is an emerging health problem, both in developing and developed countries and has an enormous economic and social impact. The objective of our study was to find the impact of insulin pump on the quality of life of patients with type 2 diabetes (T2D and compare it to the quality of life of patients with T2D using an insulin pen. Subjects and Methods: This is a case–control study which was conducted among patients with T2D presenting between November 2014 and November 2015. A total of 83 patients with T2D, using insulin pump were enrolled in the study as cases and 322 patients with T2D not using insulin pump but using insulin pens were enrolled as controls. Short form-36 quality of life questionnaire was used for data collection. Results: Mean age of patients using insulin pump was 52.49 ± 9.28 while the mean age of patients not using insulin pump was 54.72 ± 16.87. Mean score of all domains in the questionnaire was found to be higher in patients using insulin pump as compared to patients not using insulin pumps (P < 0.05. In 81.1% of the patients, the insulin pump decreased the frequency of hypoglycemic episodes. Conclusion: Insulin pump has significantly improved the quality of life of patients in terms of better self-esteem, decreased stress, and better mood. It has resulted in improved physical health, meal time flexibility, and ease of travel. It allows patient to have more active participation in social and recreational activities improving their personal and family life.

  9. [Mild preeclampsia and serum insulin values in the third pregnancy trimester].

    Science.gov (United States)

    Martínez-Abundis, E; González-Ortíz, M; Cardona-Muñoz, E G; Hernández-Chávez, A

    1998-06-01

    The purpose of this investigation was to determine the baseline insulin level in sera during fasting and after an oral glucose load in patients with mild preeclampsia and compare these values with those obtained from pregnant women with normal arterial pressure during the third trimester of their pregnancy. A cross-sectional study was realized in 38 patients with mild preeclamsia and 39 patients with normal arterial pressure values, both groups in their third trimester of pregnancy. We determined baseline arterial pressure, serum glucose and insulin, and the insulin/glucose ratio with at least 6 hours of fasting, and one hour after 50 g of glucose PO. The hypertensive group was under treatment with alfametildopa and/or hidralazine, patients with known coexistent conditions that would alter glucose or insulin levels were not included. The glucose was measured with the glucose oxidase method and the insulin levels by radioimmunoanalysis. The insulin/glucose ratio was obtained as the coefficient of insulin/glucose. Both patient groups had similar ages, number of pregnancies, gestational age and pre-pregnancy body mass index. We found no difference in glucose levels during fasting nor glucose post-load between groups. Insulin fasting levels were lower in the preeclampsia group compared with the normotensive one (7.1 +/- 3.8 vs 10.6 +/- 8.7 microU/mL, p = 0.02), however there was no difference in either group after the glucose load was administered (66.8 +/- 46.5 vs 71.0 +/- 51.9, p = N.S.). The insulin/glucose ratio had the same behavior than insulin. The hypertensive group showed a lower fasting insulin levels compared with the normotensive group. We suggest further research be done on this matter with strict selection criteria in order to emit final conclusions.

  10. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

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

  11. Insulin poisoning with suicidal intent

    Directory of Open Access Journals (Sweden)

    Abhay Gundgurthi

    2012-01-01

    Full Text Available We report a 27-year-old paramedical lady with no known comorbidities, who presented with rapid-onset coma with hypoglycemia (plasma glucose at admission was 35 mg/dL. Clinical alertness suspected and confirmed the diagnosis of exogenous insulin administration probably with suicidal intent. During the course of her ICU stay, she developed bradycardia and hypotension which required ionotropic support. She remained in coma for 90 hours. A total of 470 g of dextrose was infused until she regained consciousness. No other complications of insulin overdose were observed during her stay in the hospital. Recovery was complete without any residual neurological deficits. Insulin administration should be kept in differential diagnosis when any case presents with coma and hypoglycemia, especially in paramedical personnel.

  12. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

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

  13. Possibilities for using a temperature-controlled pyrolysis method in order to determine the bonding form of mecury in soils and sediments; Moeglichkeiten der Anwendung eines temperaturgesteuerten Pyrolyseverfahrens zur Bestimmung der Bindungsform des Quecksilbers in Boeden und Sedimenten

    Energy Technology Data Exchange (ETDEWEB)

    Biester, H.

    1994-12-31

    The bonding behaviour of mercury in solids was investigated by means of a temperature-controlled pyrolysis method. Starting from the special property of elemental mercury to evaporate already at room temperature, a method was developed which permits to characterize different mercury bonding forms on the basis of Hg evaporation behaviour from solids at continuously increased temperature. The method starts from the assumption that it is possible to thermally reduce compounded mercury and release it in elemental form. The focus of the work was on the study of Hg bonding behaviour in soils and sediments. The soil samples used were from the areas of two mercury deposits, different kyanizing sites, some former mirror factories, and a chlor-alkali electrolysis workshop. The investigated sediments are a collection of mercury-polluted samples from the rivers Elbe, Rhine, Murg, the Rio Sao Joao de Meriti (Brazil) and some brooks and rivers of the Saar-Nahe depression. (orig./EF) [Deutsch] In der vorliegenden Arbeit wurde das Bindungsverhalten von Quecksilber in Feststoffen mittels eines temperaturgesteuerten Pyrolyseverfahrens untersucht. Ausgehend von der besonderen Eigenschaften des elementaren Quecksilbers, bereits bei Zimmertemperatur zu verdampfen, wurde ein Verfahren entwickelt, das eine Charakterisierung verschiedener Quecksilberbindungsformen aufgrund des Abdampfverhaltens des Hg aus dem Feststoff unter kontinuierlicher Temperaturerhoehung zulaesst. Dem Verfahren liegt dabei die Annahme zugrunde, dass sich das Quecksilber in seinen Verbindungen thermisch reduzieren und in elementarer Form freisetzen laesst. Durch den kontinuierlichen Aufheizprozess erfolgt die Freisetzung des Quecksilbers in Abhaengigkeit von der Bindungsstaerke in unterschiedlichen Temperaturbereichen. Die Darstellung der Ergebnisse erfolgte in Form von Abdampfkurven, die die Extinktion in Abhaengigkeit von der Temperatur darstellen. Der Schwerpunkt dieser Arbeit lag auf der Untersuchung des

  14. Allergy to soft cannula of insulin pump in diabetic patient

    OpenAIRE

    Chen, Yu-Min; Huang, Hui

    2017-01-01

    Insulin pump is a relatively good choice for diabetic patients who require multiple daily injections with wide fluctuations of blood glucose. Patients using insulin pump therapy and still having uncontrolled blood glucose levels for various factors: insulin pump not working properly, insulin instability, insulin autoantibody, insulin allergy, etc. We described a 46-year-old woman with type 2 diabetes and progressive hyperglycemia after switching multiple daily insulin injections to insulin pu...

  15. Treatment Approach to Patients With Severe Insulin Resistance

    Science.gov (United States)

    Church, Timothy J.

    2016-01-01

    In Brief Patients with severe insulin resistance require >2 units/kg of body weight or 200 units/day of insulin. Yet, many patients do not achieve glycemic targets despite using very high doses of insulin. Insulin can cause weight gain, which further contributes to worsening insulin resistance. This article describes the pharmacological options for managing patients with severe insulin resistance, including the use of U-500 insulin and newer agents in combination with insulin. PMID:27092020

  16. Insulin Glulisine (rDNA origin) Injection

    Science.gov (United States)

    ... the syringe and inject the solution immediately after mixing.You can inject your insulin glulisine in your ... you have high blood sugar, the pump alarm sounds, or the insulin flow is blocked. If the ...

  17. A Systematic Review on Insulin Overdose Cases

    DEFF Research Database (Denmark)

    Johansen, Nicklas Järvelä; Christensen, Mikkel Bring

    2018-01-01

    A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications beside hypoglycaemia following large insulin overdoses is not readily apparent from the literature. This article...

  18. Insulin requirements in type 1 diabetic pregnancy

    DEFF Research Database (Denmark)

    Callesen, Nicoline; Ringholm, Lene; Stage, Edna

    2012-01-01

    To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy.......To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy....

  19. A fractional-order model for MINMOD Millennium.

    Science.gov (United States)

    Cho, Yongjin; Kim, Imbunm; Sheen, Dongwoo

    2015-04-01

    MINMOD Millennium has been widely used to estimate insulin sensitivity (SI) in glucose-insulin dynamics. In order to explain the rheological behavior of glucose-insulin we attempt to modify MINMOD Millennium with fractional-order differentiation of order α ∈ (0, 1]. We show that the new modified model has non-negative, bounded solutions and a stable equilibrium point. Quasi-optimal fractional orders and parameters are estimated by using a nonlinear weighted least-squares method, the Levenberg-Marquardt algorithm, and the fractional Adams-Bashforth-Moulton method for several subjects (normal subjects and type 2 diabetic patients). The numerical results confirm that SI is significantly lower in diabetics than in non-diabetics. In addition, we explain the new factor (τ(1 - α)) determining glucose tolerance and the relation between SI and τ(1 - α). Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Aspirin-mediated acetylation induces structural alteration and aggregation of bovine pancreatic insulin.

    Science.gov (United States)

    Yousefi, Reza; Taheri, Behnaz; Alavi, Parnian; Shahsavani, Mohammad Bagher; Asadi, Zahra; Ghahramani, Maryam; Niazi, Ali; Alavianmehr, Mohammad Mehdi; Moosavi-Movahedi, Ali Akbar

    2016-01-01

    The simple aggregation of insulin under various chemical and physical stresses is still an important challenge for both pharmaceutical production and clinical formulation. In the storage form, this protein is subjected to various chemical modifications which alter its physicochemical and aggregation properties. Aspirin (acetylsalicylic acid) which is the most widely used medicine worldwide has been indicated to acetylate a large number of proteins both in vitro and in vivo. In this study, as insulin treated with aspirin at 37°C, a significant level of acetylation was observed by flourescamine and o-phthalaldehyde assay. Also, different spectroscopic techniques, gel electrophoresis, and microscopic assessment were applied to compare the structural variation and aggregation/fibrillation propensity among acetylated and non-acetylated insulin samples. The results of spectroscopic assessments elucidate that acetylation induces insulin unfolding which is accompanied with the exposure of protein hydrophobic patches, a transition from alpha-helix to beta-sheet and increased propensity of the protein for aggregation. The kinetic studies propose that acetylation increases aggregation rate of insulin under both thermal and chemical stresses. Also, gel electrophoresis and dynamic light scattering experiments suggest that acetylation induces insulin oligomerization. Additionally, the results of Thioflavin T fluorescence study, Congo red absorption assessment, and microscopic analysis suggest that acetylation with aspirin enhances the process of insulin fibrillation. Overall, the increased susceptibility of acetylated insulin for aggregation may reflect the fact that this type of modification has significant structural destabilizing effect which finally makes the protein more vulnerable for pathogenic aggregation/fibrillation.

  1. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Almind, K; Bjørbaek, C; Vestergaard, H

    1993-01-01

    Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate...

  2. Comparison of metformin and insulin versus insulin alone for type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn

    2012-01-01

    To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes.......To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes....

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

    NARCIS (Netherlands)

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

    OBJECTIVE: In addition to insulin's metabolic actions, insulin can dilate arterioles which increase blood flow to metabolically active tissues. This effect is blunted in insulin-resistant subjects. Insulin's effect on SVR, determined by resistance arterioles, has, however, rarely been examined

  4. Redox regulation of insulin degradation by insulin-degrading enzyme.

    Directory of Open Access Journals (Sweden)

    Crystal M Cordes

    Full Text Available Insulin-degrading enzyme (IDE is a thiol sensitive peptidase that degrades insulin and amyloid β, and has been linked to type 2 diabetes mellitus and Alzheimer's disease. We examined the thiol sensitivity of IDE using S-nitrosoglutathione, reduced glutathione, and oxidized glutathione to distinguish the effects of nitric oxide from that of the redox state. The in vitro activity of IDE was studied using either partially purified cytosolic enzyme from male Sprague-Dawley rats, or purified rat recombinant enzyme. We confirm that nitric oxide inhibits the degrading activity of IDE, and that it affects proteasome activity through this interaction with IDE, but does not affect the proteasome directly. Oxidized glutathione inhibits IDE through glutathionylation, which was reversible by dithiothreitol but not by ascorbic acid. Reduced glutathione had no effect on IDE, but reacted with partially degraded insulin to disrupt its disulfide bonds and accelerate its breakdown to trichloroacetic acid soluble fragments. Our results demonstrate the sensitivity of insulin degradation by IDE to the redox environment and suggest another mechanism by which the cell's oxidation state may contribute to the development of, and the link between, type 2 diabetes and Alzheimer's disease.

  5. Insulin Pump Safety Meeting: Summary Report

    OpenAIRE

    Klonoff, David C.; Reyes, Juliet S.

    2009-01-01

    Diabetes Technology Society convened a panel of insulin pump experts in Bethesda, Maryland, on November 12, 2008, at the request of the Food and Drug Administration. The group consisted of physicians, nurses, diabetes educators, and engineers from across the United States. The panel members (1) discussed safety features of insulin pump therapy and (2) recommended adjustments to current insulin pump design and use to enhance overall safety. Software and hardware features of insulin pumps were ...

  6. Modern basal insulin analogs: An incomplete story

    OpenAIRE

    Singh, Awadhesh Kumar; Gangopadhyay, Kalyan Kumar

    2014-01-01

    The currently available basal insulin does not completely mimic the endogenous insulin secretion. This has continued to promote the search for ideal basal insulin. The newer basal insulin have primarily focused on increasing the duration of action, reducing variability, and reducing the incidence of hypoglycemia, particularly nocturnal. However, the changing criteria of hypoglycemia within a short span of a few years along with the surprising introduction of major cardiac events as another ou...

  7. Serum leptin and insulin tests in obesity

    International Nuclear Information System (INIS)

    Yang Yin; Jiang Xiaojin; Leng Xiumei

    2001-01-01

    Objective: To study the clinical significance and the relations of leptin and insulin on obesity group. Methods: Leptin and insulin were tested with radioimmunoassay (RIA) in pre-obesity group and obesity group respectively. Results: Serum leptin and insulin levels were significantly elevated in obesity group compare with the controls (P<0.01). Conclusion: Changing with insulin, the elevation of leptin in obesity group has been identified as an important agent of diabetes mellitus (DM)

  8. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

    Czech Academy of Sciences Publication Activity Database

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, C. J.; Turkenburg, J. P.; Jiráček, Jiří; Brzozowski, A. M.

    2014-01-01

    Roč. 70, č. 10 (2014), s. 2765-2774 ISSN 0907-4449 R&D Projects: GA ČR GPP207/11/P430; GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : insulin * insulin receptor * complex * active form * analog * structure Subject RIV: CE - Biochemistry Impact factor: 7.232, year: 2013

  9. Assessing health systems for type 1 diabetes in sub-Saharan Africa: developing a 'Rapid Assessment Protocol for Insulin Access'

    DEFF Research Database (Denmark)

    Beran, David; Yudkin, John S; de Courten, Maximilian

    2006-01-01

    In order to improve the health of people with Type 1 diabetes in developing countries, a clear analysis of the constraints to insulin access and diabetes care is needed. We developed a Rapid Assessment Protocol for Insulin Access, comprising a series of questionnaires as well as a protocol...

  10. Analysis of the local dynamics of human insulin and a rapid-acting insulin analog by hydrogen/deuterium exchange mass spectrometry.

    Science.gov (United States)

    Nakazawa, Shiori; Ahn, Joomi; Hashii, Noritaka; Hirose, Kenji; Kawasaki, Nana

    2013-06-01

    Human insulin and insulin lispro (lispro), a rapid-acting insulin analog, have identical primary structures, except for the transposition of a pair of amino acids. This mutation results in alterations in their higher order structures, with lispro dissociating more easily than human insulin. In our previous study performed using hydrogen/deuterium exchange mass spectrometry (HDX/MS), differences were observed in the rates and levels of deuteration among insulin analog products, which were found to be related to their self-association stability. In this study, we carried out peptide mapping of deuterated human insulin and lispro to determine the regions responsible for these deuteration differences and to elucidate the type of structural changes that affect their HDX reactivity. We identified A3-6 and B22-24 as the 2 regions that showed distinct differences in the number of deuterium atoms incorporated between human insulin and lispro. These regions contain residues that are thought to participate in hexamerization and dimerization, respectively. We also determined that over time, the differences in deuteration levels decreased in A3-6, whereas they increased in B22-24, suggesting a difference in the dynamics between these 2 regions. This article is part of a Special Issue entitled: Mass spectrometry in structural biology. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  13. Lipohypertrophy – a complication of insulin injections

    African Journals Online (AJOL)

    suggested as a cause – lipoatrophy may result from a local immune reaction against impurities of the insulin preparations, while lipohypertrophy may result from the local trophic action of insulin.7,8. Furthermore .... 106-110. 9. Ganda OP. Lipoatrophy, lipodystrophy and insulin resistance. Ann Intern Med 2000;. 133: 304-305 ...

  14. Insulin sensitivity : modulation by the brain

    NARCIS (Netherlands)

    Coomans, Claudia Pascalle

    2012-01-01

    The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated

  15. Insulin inhibits tissue factor expression in monocytes

    NARCIS (Netherlands)

    Gerrits, A. J.; Koekman, C. A.; Yildirim, C.; Nieuwland, R.; Akkerman, J. W. N.

    2009-01-01

    Summary Objectives: Platelets from healthy subjects are inhibited by insulin but type 2 diabetes mellitus (T2DM) platelets have become insulin-resistant which might explain their hyperactivity. In the present study we investigated whether monocytes are responsive to insulin. Methods and Results:

  16. Insulin Resistance: From Theory To Practice

    OpenAIRE

    Srinivas Kakkilaya Bevinje

    2006-01-01

    Insulin resistance is at the core of the well recognised metabolic syndrome and possibly many other ailments commonly seen in the modern society. While the quantification of insulin resistance remains a difficult task, the problems associated with it are increasing in epidemic proportions. Need of the hour therefore is to develop concise dietary and pharmacotherapeutic guidelines for prevention and management of insulin resistance

  17. The future of basal insulin supplementation

    NARCIS (Netherlands)

    Simon, Airin C. R.; DeVries, J. Hans

    2011-01-01

    This review presents an overview of the candidates for an improved basal insulin in the pharmaceutical pipeline. The first new basal insulin to enter the market is most likely insulin degludec (IDeg), currently reporting in phase 3 of development, from Novo Nordisk (Bagsvaerd, Denmark). IDeg has a

  18. Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial

    NARCIS (Netherlands)

    van Bon, Arianne C.; Bode, Bruce W.; Sert-Langeron, Caroline; DeVries, J. Hans; Charpentier, Guillaume

    2011-01-01

    In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label,

  19. Insulin resistance in Nigerians with essential hypertension

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... parameters, blood pressure, fasting glucose and insulin were measured. Homeostasis model ... Results: The hypertensive subjects had significantly higher fasting insulin and HOMA-IR compared with normotensives. (p =0.02 and 0.04) ..... demonstrated the benefit of early interventions to improve insulin ...

  20. Cell surface alteration in Epstein-Barr virus-transformed cells from patients with extreme insulin resistance

    International Nuclear Information System (INIS)

    Gorden, D.L.; Robert, A.; Moncada, V.Y.; Taylor, S.I.; Muehlhauser, J.C.; Carpentier, J.L.

    1990-01-01

    An abnormality was detected in the morphology of the cell surface of Epstein-Barr virus-transformed lymphocytes of patients with genetic forms of insulin resistance. In cells from two patients with leprechaunism and two patients with type A extreme insulin resistance, scanning electron microscopy demonstrated a decrease in the percentage of the cell surface occupied by microvilli in cells from the patients with leprechaunism and type A insulin resistance compared with control cells. When cells from a healthy control subject and one of the patients with leprechaunism (Lep/Ark-1) were incubated with 125 I-labeled insulin, there was a decrease in the percentage of 125 I-insulin associated with microvilli on the cell surface. Thus, the decreased localization of insulin receptors with the microvillous region of the cell surface was in proportion to the decrease in microvilli

  1. Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

    Directory of Open Access Journals (Sweden)

    Pešić Milica

    2007-01-01

    Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  2. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    OpenAIRE

    Castillo, C; Bogardus, C; Bergman, R; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  3. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

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

  4. Microbial Modulation of Insulin Sensitivity

    NARCIS (Netherlands)

    Khan, Muhammad Tanweer; Nieuwdorp, Max; Bäckhed, Fredrik

    2014-01-01

    The gut microbiota has emerged as an integral factor that impacts host metabolism and has been suggested to play a vital role in metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In humans, cross-sectional studies have identified microbiota profiles

  5. NGA/Insulin receptor scanning

    International Nuclear Information System (INIS)

    Kurtaran, A.; Virgolini, I.

    1994-01-01

    Tc-99m-galactosyl-neoglycoalbumin (NGA) is one of the first receptor-based radiopharmaceuticals which specifically recognizes the hepatic binding protein (HBP) located on the surface of the hepatocytes. The exclusive interactin of NGA with HBP provided the basis for a kinetic model for the evaluation hepatocellular function. During the last years we have used NGA in more than 300 patients with various liver diseases including liver cirrhosis (Stages Child A to Child C), viral hepatitis, and carcinomas. In these studies, the calculated HBP densities, after i.v.-injection of Tc-99m-NGA, significantly correlated with the clinical course of the diseases. Furthermore, similar to conventional Tc-colloid, NGA provided excellent demonstration of 'cold spots' for hepatic masses. In a further approach we used another hepatocyte receptor-seeking radioligand, I-123-Tyr-A14- insulin, and found, that its in vitro-binding to hepatocellular carcinomas is greatly enhanced over normal hepatic tissue. On this basis, we developed a double-tracer method using NGA and insulin in a single study. Thus, areas of 'cold spots' identifying hepatic masses on NGA scans, take up I-123-Tyr-A14-insulin immediately after i.v.-injection. This was true for hepatocellular hepatomas, but not for adenocarcinomas. In conclusion, NGA/insulin receptor scanning could be a novel and save method for the demonstration of hepatocellular hepatomas. (author)

  6. Insulin and the Burned Patient

    Science.gov (United States)

    2007-01-01

    Substrate mobilization by glycogenolysis and gluconeogenesis is similarly up- regulated in the face of high serum glu- cose (26). The complete mechanism of...Akt/PKB regulates skeletal muscle growth or loss, providing a link between insulin resistance and cat - abolic muscle wasting in burns (27). Other

  7. Obesity genes and insulin resistance.

    Science.gov (United States)

    Belkina, Anna C; Denis, Gerald V

    2010-10-01

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

  8. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

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

  9. Crystallization of bovine insulin on a flow-free droplet-based platform

    Science.gov (United States)

    Chen, Fengjuan; Du, Guanru; Yin, Di; Yin, Ruixue; Zhang, Hongbo; Zhang, Wenjun; Yang, Shih-Mo

    2017-03-01

    Crystallization is an important process in the pharmaceutical manufacturing industry. In this work, we report a study to create the zinc-free crystals of bovine insulin on a flow-free droplet-based platform we previously developed. The benefit of this platform is its promise to create a single type of crystals under a simpler and more stable environment and with a high throughput. The experimental result shows that the bovine insulin forms a rhombic dodecahedra shape and the coefficient variation (CV) in the size of crystals is less than 5%. These results are very promising for the insulin production.

  10. Tomato leaf curl Kerala virus (ToLCKeV AC3 protein forms a higher order oligomer and enhances ATPase activity of replication initiator protein (Rep/AC1

    Directory of Open Access Journals (Sweden)

    Mukherjee Sunil K

    2010-06-01

    Full Text Available Abstract Background Geminiviruses are emerging plant viruses that infect a wide variety of vegetable crops, ornamental plants and cereal crops. They undergo recombination during co-infections by different species of geminiviruses and give rise to more virulent species. Antiviral strategies targeting a broad range of viruses necessitate a detailed understanding of the basic biology of the viruses. ToLCKeV, a virus prevalent in the tomato crop of Kerala state of India and a member of genus Begomovirus has been used as a model system in this study. Results AC3 is a geminiviral protein conserved across all the begomoviral species and is postulated to enhance viral DNA replication. In this work we have successfully expressed and purified the AC3 fusion proteins from E. coli. We demonstrated the higher order oligomerization of AC3 using sucrose gradient ultra-centrifugation and gel-filtration experiments. In addition we also established that ToLCKeV AC3 protein interacted with cognate AC1 protein and enhanced the AC1-mediated ATPase activity in vitro. Conclusions Highly hydrophobic viral protein AC3 can be purified as a fusion protein with either MBP or GST. The purification method of AC3 protein improves scope for the biochemical characterization of the viral protein. The enhancement of AC1-mediated ATPase activity might lead to increased viral DNA replication.

  11. Micro metal forming

    CERN Document Server

    2013-01-01

    Micro Metal Forming, i. e. forming of parts and features with dimensions below 1 mm, is a young area of research in the wide field of metal forming technologies, expanding the limits for applying metal forming towards micro technology. The essential challenges arise from the reduced geometrical size and the increased lot size. In order to enable potential users to apply micro metal forming in production, information about the following topics are given: tribological behavior: friction between tool and work piece as well as tool wear mechanical behavior: strength and formability of the work piece material, durability of the work pieces size effects: basic description of effects occurring due to the fact, that the quantitative relation between different features changes with decreasing size process windows and limits for forming processes tool making methods numerical modeling of processes and process chains quality assurance and metrology All topics are discussed with respect to the questions relevant to micro...

  12. Unintended Insulin Pump Delivery in Hyperbaric Conditions.

    Science.gov (United States)

    Bertuzzi, Federico; Pintaudi, Basilio; Bonomo, Matteo; Garuti, Fabio

    2017-04-01

    Unintended pump insulin delivery was reported to occur as a consequence of decreased atmospheric pressure, probably mediated by air bubble formation and the expansion of existing bubbles. This observation has been used to explain some hypoglycemic episodes occurring in patients on insulin pump treatment in between 1 and 1 h 45 min after the flight takeoff. New models of insulin pumps have been introduced in the market, most of them are waterproof certified. It is not clear if in these new pumps the influence of atmospheric pressure changes on the insulin delivery is still present. Moreover, there are no evidences related to the insulin pump operations in hyperbaric conditions, like as during diving activities. Our aim is therefore to verify the eventual variation of insulin pump delivery determined by atmospheric pressure changes in hyperbaric conditions. Three new models of insulin pumps were tested in hyperbaric conditions at a flow rate of 2 U/h. Atmospheric pressure variation affected pump insulin release. An increase in the atmospheric pressure from 1 to 1.3 atmosphere (ATA) induced a decrease of pump basal insulin release (about -0.2 U/10 min); conversely, when the atmospheric pressure returned from 1.3 to 1 ATA, an unintended insulin delivery was observed (about +0.3 U/10 min). This phenomenon appeared to be independent of the insulin pump rate and dependent on the presence of air bubbles within the insulin tube setting and cartridge. Unintended insulin delivery driven by atmospheric pressure changes in hyperbaric conditions occurred in the new insulin pumps available. Patients should pay attention to possible variation of insulin rate during the flight or during diving activities.

  13. Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes.

    Science.gov (United States)

    Manowsky, Julia; Camargo, Rodolfo Gonzalez; Kipp, Anna P; Henkel, Janin; Püschel, Gerhard P

    2016-06-01

    Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. Copyright © 2016 the American Physiological Society.

  14. Qualitative study into quality of life issues surrounding insulin pump use in type 1 diabetes

    DEFF Research Database (Denmark)

    Barnard, Katharine D.; Skinner, T. Chas

    2007-01-01

    Currently, there is a need for qualitative research about how insulin pump therapy changes quality of life, which is significant to people with type 1 diabetes. This study aimed to elicit thd experiences of current insulin pump users in order to discover the therapy's benefits, downsides and effect...... on their quality of life. A qualitative approach was taken in order to reveal subjective experiences. This research will inform future research and assist with policy and guideline development by health care providers about pump therapy. Participants were briefly interviewed by telephone about their experiences...... of living with an insulin pump. Four questions were asked. These covered the benefits of pump use, effects on quality of life, whether participants experienced downsides to using a pump and any other issues participants wished to raise. In all, 80 insulin pump users participated in the, study. All 80...

  15. Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

    Science.gov (United States)

    Renard, Eric; Place, Jerome; Cantwell, Martin; Chevassus, Hugues; Palerm, Cesar C.

    2010-01-01

    OBJECTIVE Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS Two-day closed-loop therapy (except for a 15-min premeal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean ± SEM percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was significantly higher (39.1 ± 4.5 vs. 27.7 ± 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4–6.6 mmol/l range (46.3 ± 5.3 vs. 28.6 ± 7.4, P = 0.025) and lower mean blood glucose levels (6.9 ± 0.3 vs. 7.9 ± 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. CONCLUSIONS Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the premeal bolus in terms of timing and amount warrant further research. PMID:19846796

  16. Specific uptake, dissociation, and degradation of 125I-labeled insulin in isolated turtle (Chrysemys dorbigni) thyroid glands

    International Nuclear Information System (INIS)

    Marques, M.; da Silva, R.S.; Turyn, D.; Dellacha, J.M.

    1985-01-01

    Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with 125 I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of bovine insulin that inhibited 50% of the 125 I-insulin uptake was 2 micrograms/ml of incubation medium. Most of the radioactive material (71%) extracted from the gland, after 30 min incubation with 125 I-insulin, eluted in the same position as labeled insulin on Sephadex G-50. Only 24% eluted in the salt position. After 240 min incubation, increased amount of radioactivity appeared in the Na 125 I position. When bovine insulin was added together with the labeled hormone, a substantial reduction of radioactivity was observed in the insulin and Na 125 I elution positions. Dissociation studies were performed at 6 degrees in glands preincubated with 125 I-insulin either at 24 or 6 degrees. The percentage of trichloroacetic acid (TCA)-soluble radioactive material in the dissociation medium increased with incubation time at both temperatures. However, the degradation activity was lower at 6 than at 24 degrees. The addition of bovine insulin to the incubation buffer containing 125 I-insulin reduced the radioactive degradation products in the dissociated medium. Chloroquine or bacitracin inhibited the degradation activity. Incubation of thyroid glands with 125 I-hGH or 125 I-BSA showed values of uptake, dissociation, and degradation similar to those experiments in which an excess of bovine insulin was added together with the labeled hormone. Thus, by multiple criteria, such as specific uptake, dissociation, and degradation, the presence of insulin-binding sites in the turtle thyroid gland may be suggested

  17. A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin

    DEFF Research Database (Denmark)

    Hansen, L; Hansen, T; Vestergaard, H

    1995-01-01

    The regulatory G-subunit of the glycogen-associated form of protein phosphatase 1 (PP1) plays a crucial part in muscle tissue glycogen synthesis and breakdown. As impaired insulin stimulated glycogen synthesis in peripheral tissues is considered to be a pathogenic factor in subsets of non......-insulin-dependent diabetes mellitus (NIDDM) and obesity, the G-subunit of PP1 should be viewed as a candidate gene for inherited insulin resistance. When applying heteroduplex formation analysis and nucleotide sequencing of PP1G-subunit cDNA from 30 insulin resistant white NIDDM patients two cases were identified...... as heterozygous carriers of an Asp905 --> Tyr substitution. The carrier prevalence of the PP1G-subunit variant was 18% in 150 healthy subjects and 13% in 313 NIDDM subjects (chi 2 = 1.94, p = 0.16). Twenty-seven healthy subjects volunteered for a 4 h euglycaemic, hyperinsulinaemic clamp in combination...

  18. Effects of Everyday Life Events on Glucose, Insulin, and Glucagon Dynamics in Continuous Subcutaneous Insulin Infusion–Treated Type 1 Diabetes: Collection of Clinical Data for Glucose Modeling

    DEFF Research Database (Denmark)

    Schmidt, Signe; Finan, Daniel Aaron; Duun-Henriksen, Anne Katrine

    2012-01-01

    metabolism, we designed and conducted a clinical study.Methods: Patients with insulin pump–treated T1D were recruited to perform everyday life events on two separate days. During the study, patients wore their insulin pumps and, in addition, a continuous glucose monitor and an activity monitor to estimate...... energy expenditure. The sequence of everyday life events was predetermined and included carbohydrate intake, insulin boluses, and bouts of exercise; the events were introduced, temporally separated, in different orders and in different quantities. Throughout the study day, 10-min plasma glucose...... measurements were taken, and samples for plasma insulin and glucagon analyses were obtained every 10 min for the first 30 min after an event and subsequently every 30 min.Results: We included 12 patients with T1D (75% female, 34.3±9.1 years old [mean±SD], hemoglobin A1c 6.7±0.4%). During the 24 study days we...

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  20. Insulin aggregation tracked by its intrinsic TRES

    Science.gov (United States)

    Chung, Li Hung C.; Birch, David J. S.; Vyshemirsky, Vladislav; Ryadnov, Maxim G.; Rolinski, Olaf J.

    2017-12-01

    Time-resolved emission spectra (TRES) have been used to detect conformational changes of intrinsic tyrosines within bovine insulin at a physiological pH. The approach offers the ability to detect the initial stages of insulin aggregation at the molecular level. The data analysis has revealed the existence of at least three fluorescent species undergoing dielectric relaxation and significant spectral changes due to insulin aggregation. The results indicate the suitability of the intrinsic TRES approach for insulin studies and for monitoring its stability during storage and aggregation in insulin delivery devices.

  1. Insulin resistance and bone: a biological partnership.

    Science.gov (United States)

    Conte, Caterina; Epstein, Solomon; Napoli, Nicola

    2018-04-01

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

  2. Insulin resistance in drug naive patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kostić Smiljana

    2017-01-01

    Full Text Available Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS, the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR and reduced insulin sensitivity (IS in untreated patients with MS could play a role in disease progression and degree of functional disability. Methods. The study included 31 patients with relapsing-remitting (RR MS and 14 healthy controls from the same geographic area matched by age, ethnicity and number of smokers. The glucose tolerance, IS, and IR were examined using an oral glucose tolerance test (OGTT and using basal plasma glucose and insulin levels. The functional disability and disease progression were evaluated by the Expanded Disability Status Scale (EDSS and Multiple Sclerosis Severity Score (MSSS. Results. The MS patients tolerated glucose equally well as the healthy controls. Basal concentrations of insulin were significantly higher in the MS group (p < 0.05, as well as insulin plasma level 30 min after oral glucose load (p < 0.01. The patients with MS had significantly higher values of homeostasis model assessment indexes of IR (HOMA-IR (p = 0.027; p = 0.028. The percentage of IS (HOMA2 %S and whole body IS index (ISI Matsuda showed significantly lower values in the MS patients than in the controls (p = 0.005; p = 0.001. The insulinogenic index in the first 30 min of OGTT was significantly higher in MS patients (p = 0.005. The measures of functional disability and MS progression did not correlate significantly with the investigated parameters of IR and IS indexes. Conclusion. This study demonstrates for the first time the existence of hyperinsulinemia, reduced insulin sensitivity and normal glucose tolerance that indicate the initial

  3. Order Aggressiveness and Order Book Dynamics

    OpenAIRE

    Anthony D. Hall; Nikolaus Hautsch

    2004-01-01

    In this paper, we study the determinants of order aggressiveness and traders' order submission strategy in an open limit order book market. Using order book data from the Australian Stock Exchange, we model traders' aggressiveness in market trading, limit order trading as well as in order cancellations on both sides of the market using a six-dimensional autoregressive intensity model. The information revealed by the open order book plays an important role in explaining the degree of order agg...

  4. Selective Insulin Resistance in the Kidney

    Science.gov (United States)

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

    2016-01-01

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

  5. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

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

  6. [Serious medication order errors at hospitals].

    Science.gov (United States)

    Andersen, Mette Lehmann; Søndergaard, Jens; Hallas, Jesper; Pedersen, Anette; Hellebek, Annemarie

    2009-03-09

    Medication order errors are frequent in Denmark. It is necessary to know the reasons why these errors happen to be able to implement initiatives limiting medication order errors. In this study we analyzed 811 medications order errors, which were reported as unintended events. The medication order errors were associated with at total of 98 medicinal product; hence nine medicinal products caused 18 errors with severe or catastrophic harm to patients. 46.0% of the errors were incorrect medicinal product, 47.7% were incorrect dosage and 6.3% of the orders were double ordering. Penicillin and warfarin were the most frequently involved medicinal products. The products that most frequently caused severe or catastrophic patient harm were insulin and warfarin. The most frequent errors were "no medicinal product prescribed" and "incorrect medicinal product". The errors with the most severe consequences for the patients were due to "medication was not discontinued" (sevoflurane and warfarin) and "poor patient compliance" (warfarin and insulin). A common feature concerning the errors' origin was incorrect handling of information. Specific initiatives should be taken to counter the above-mentioned problems and reduce the occurrence of medication order errors. Such measures may comprise control, medication reconciliation and imposition of clinical decision support.

  7. C-Peptide, Baseline and Postprandial Insulin Resistance after a Carbohydrate-Rich Test Meal - Evidence for an Increased Insulin Clearance in PCOS Patients?

    Science.gov (United States)

    Stassek, J; Erdmann, J; Ohnolz, F; Berg, F D; Kiechle, M; Seifert-Klauss, V

    2017-01-01

    Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study ( L ifestyle I ntervention for Patients with Polycystic Ovary Syndrome [ PCOS ]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients.

  8. Consensus on Insulin Dose Modification During Fasting in Type 2 Diabetes.

    Science.gov (United States)

    Unnikrishnan, A G; Lodha, Sailesh; Sharma, S K

    2017-03-01

    Fasting for patients with type 2 diabetes mellitus (T2DM) carries a risk of an assortment of complications. The decision of T2DM patient to fast should be made after sufficient discussion with physician regarding the risks involved. The current consensus is developed to help physicians manage T2DM patients during fasting. To provide simple and easily implementable guidelines on insulin dose modification during fasting in T2DM patients. The expert group committee discussed and proposed six recommendations for the use of insulin regimens during fasting. The recommendations were proposed on diet, exercise and categorization of risks during fast, breaking fast, dose modification of basal insulins, premix insulins and prandial insulins. All these recommendations were based on established guidelines and published scientific literature. These evidences were then factored into the national context based on the expert committee representative's patient-physician experience in their clinical practice and common therapeutic practices followed in India to successfully achieve optimal glucose control. The final consensus-based recommendations were proposed and collectively recorded for each insulin regimen. Recommendations based on insulin dose modification during fasting in T2DM patients has been developed. Patients with diabetes, who fast are recommended to keep themselves hydrated, consume low glycaemic and high fibre food but, avoid sugary and caffeinated drinks along with fried foods. The main goal of insulin therapy during fasting is to provide adequate insulin to prevent post meal hyperglycaemia and prevent hypoglycaemia during fast. We hope that the consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners to initiate and intensify insulin therapy in T2DM patients in order to successfully complete fasting without much complication.

  9. Influence of glucosamine on the bioactivity of insulin delivered subcutaneously and in an oral nanodelivery system

    Science.gov (United States)

    Al-Kurdi, Zakieh I; Chowdhry, Babur Z; Leharne, Stephen A; Qinna, Nidal A; Al Omari, Mahmoud MH; Badwan, Adnan A

    2015-01-01

    The aim of the work reported herein was to study the effect of glucosamine HCl (GlcN·HCl) on the bioactivity (BA) of insulin, administered via subcutaneous (SC) and oral routes, in adult male Sprague Dawley rats. The oral insulin delivery system (insulin–chitosan reverse micelle [IC-RM]) was prepared by solubilizing insulin–chitosan (13 kDa) polyelectrolyte complex in a RM system consisting of oleic acid, PEG-8 caprylic/capric glycerides, and polyglycerol-6-dioleate. The BA of insulin in vivo was evaluated by measuring blood glucose level using a blood glucose meter; the results revealed that the extent of hypoglycemic activity of SC insulin was GlcN·HCl dose dependent when they were administered simultaneously. A significant reduction in blood glucose levels (P<0.05) was found for the insulin:GlcN·HCl at mass ratios of 1:10 and 1:20, whereas lower ratios (eg, 1:1 and 1:4) showed no significant reduction. Furthermore, enhancement of the action of SC insulin was achieved by oral administration of GlcN·HCl for 5 consecutive days prior to insulin injection (P<0.05). For oral insulin administration via the IC-RM system, the presence of GlcN·HCl increased the hypoglycemic activity of insulin (P<0.05). The relative BA were 6.7% and 5.4% in the presence and absence of GlcN·HCl (ie, the increase in the relative BA was approximately 23% due to incorporating GlcN·HCl in the IC-RM system), respectively. The aforementioned findings offer an opportunity to incorporate GlcN·HCl in oral insulin delivery systems in order to enhance a reduction in blood glucose levels. PMID:26640369

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

    International Nuclear Information System (INIS)

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

    2012-10-01

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

  11. Postirradiation utility of insulin in radiotherapy

    International Nuclear Information System (INIS)

    Chaudhari, C.A.; Shenoy, C.N.; Chaubal, K.A.

    1987-01-01

    The radiobiological effect of insulin was studied under laboratory conditions to find its utility in radiotherapy. Balb/c mice receiving injections of insulin after irradiation exhibited rapid recovery from the radiation effect. This was evident from the data on their life span, organ weights and spleen colony assay studies, carried out under conditions of whole body and partial body irradiation. This trend was absent in mice injected with insulin before irradiation. The results of experiments on E. coli B/r and HA cells irradiated in the presence of insulin under oxic conditions suggest a radioprotective effect of insulin. The E. coli B/r cells irradiated in the presence of insulin under hypoxia, however, showed a moderate radiosensitizing effect of insulin. (author). 4 figs., 7 tabs., 20 refs

  12. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

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

  13. Insulin prices, availability and affordability: a cross-sectional survey of pharmacies in Hubei Province, China.

    Science.gov (United States)

    Liu, Chenxi; Zhang, Xinping; Liu, Chaojie; Ewen, Margaret; Zhang, Zinan; Liu, Guoqin

    2017-08-24

    Poor access to affordable insulin results in serious and needless complications and premature deaths for those with diabetes who need this essential medicine. To help address this issue, we assessed insulin availability, prices, affordability and price components in Hubei Province as China has the heaviest burden of diabetes globally. In 2016, insulin availability and price data was collected in the capital and five other cities. A total of 30 public sector outlets (hospitals and primary care institutions) and 30 private pharmacies were sampled, using an adaptation of the World Health Organization/Health Action International methodology, Data was collected for all human and analogue insulins in stock, then analyzed by type (prandial, basal or pre-mixed) and duration of action. Prices were expressed as Median Price Ratios (MPRs) to Australian PBS prices. Price components were tracked for five insulin products in two cities.. Affordability was assessed as the number of days' wages of the lowest paid unskilled government worker needed to purchase 10 ml 100 IU/ml (approximately 30 days' supply). Mean availability was highest in public hospitals for prandial (70%), basal (80%) and pre-mixed insulin (90%). In primary care institutions and private pharmacies mean availability ranged from 10% to 33%. Median prices of all insulin types were higher that Australian PBS prices in all three sectors for human and analogue insulins (ranging from1.36-2.59 times). Patients have to pay 4 to 16 days' wages to purchase a month's treatment depending on the insulin type and sector. The largest component of the patient price was the manufacturers' selling price (60%). Taxes in the form of import duties and VAT are applied in some sectors. The availability of insulin in primary care institutions and private retail pharmacies was very low in Hubei. Only public hospitals had good insulin availability. Insulin prices were high in all sectors making this life-saving medicine unaffordable

  14. Reconstruction of the insulin secretion rate by Bayesian deconvolution

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Højbjerre, Malene

    of the insulin secretion rate (ISR) can be done by solving a highly ill-posed deconvolution problem. We present a Bayesian methodology for the estimation of scaled densities of phase-type distributions via Markov chain Monte Carlo techniques, whereby closed form evaluation of ISR is possible. We demonstrate...... the methodology on simulated data concluding that the method seems as a promising alternative to existing methods where the ISR is considered as piecewise constant....

  15. Long-term antidiabetic activity of vanadyl after treatment withdrawal: restoration of insulin secretion?

    Science.gov (United States)

    Cros, G H; Cam, M C; Serrano, J J; Ribes, G; McNeill, J H

    In its vanadate (V5+) or vanadyl (V4+) forms, vanadium has been demonstrated to possess antidiabetic activity. Oral treatment of streptozotocin (STZ)-diabetic animals with either form is associated with correction of hyperglycemia, and prevention of diabetes-induced complications, although weight gain is unaffected. Vanadium treatment of non-diabetic animals lowers plasma insulin levels by reducing insulin demand, as these animals remain normoglycemic. These results suggest that vanadium has in vivo insulin-mimetic or insulin-enhancing effects, in agreement with several in vitro observations. Chronic treatment with vanadium has also been shown to result in sustained antidiabetic effects in STZ-diabetic animals long after treatment has ceased. Thus, at 13 weeks after withdrawal from treatment, corrected animals had normalized glucose and weight gain, and improved basal insulin levels. In addition, near-normal glucose tolerance was found despite an insignificant insulin response. Since vanadium accumulates in several tissue sites (e.g. bone, kidney) when pharmacological doses are administered, it is possible that stored vanadium may be important in maintaining near-normal glucose tolerance at least in the short-term following withdrawal from treatment. Recently, following withdrawal of vanadyl treatment up to 30 weeks, diabetic animals which had remained normoglycemic and had normalized glucose tolerance showed improvements in plasma insulin levels both in the basal state and in response to oral glucose, as compared to those which had reverted to hyperglycemia. The observed significant improvements in insulin capacity over the long-term ( > 3 months) suggests that a restored and/or preserved insulin secretion may be essential for maintained reversal of the diabetic state over a prolonged period after treatment is withdrawn.

  16. Getting closer to physiologic insulin secretion.

    Science.gov (United States)

    Heise, Tim

    2007-01-01

    The goal of insulin replacement therapy in diabetes mellitus (DM) is to recreate a normal physiologic insulin supply throughout the day. This article reviewed the use of rapid acting insulin analogues in recreating physiologic postprandial insulin responses. This review article was based on a presentation at a satellite symposium entitled "Realising the Value of Modern Insulins: Reaching Further with Rapid-Acting Insulin Analogues" that was convened during the XIXth World Diabetes Congress, December 3, 2006, in Cape Town, South Africa. In the context of mealtime insulin supply, recreating physiologic postprandial insulin responses requires rapid availability of insulin within a short time of eating and a duration of action that does not extend into the late postprandial period. Conventional human insulin is not ideally suited to SC injection, with its slow onset of action and dose-dependent duration of action. The rapid-acting insulin analogues have been designed to address these deficiencies, with more rapid onset of action, higher maximal effects, and consequently better postprandial glycemic control. These properties have been reported in patients with type 1 and type 2 DM, as well as in nondiabetic individuals in euglycemic clamp studies. Rapid-acting insulin analogues are also of particular interest in people with diabetic nephropathy, women with gestational DM, and elderly patients with DM. Compared with soluble human (regular) insulin, rapid-acting insulin analogues have a more rapid onset of action and a shorter duration of action. Their potential in special patient groups is now being established in clinical research and in everyday practice.

  17. A radioreceptor assay for insulin: direct measurement of dog pancreatic vein serum insulin.

    Science.gov (United States)

    Kabuto, M; Suzuki, K; Ohsawa, N; Kosaka, K

    1977-04-01

    A simple radioreceptor assay for insulin rat liver membranes as receptor sites, with sufficient specificity precision, and sensitivity to detect 10 ng or 276 muU/ml of serum insulin, has been developed. In the presence of standard porcine insulin at the concentration of 1.0 ng/tube, approximately 8% of 125I-porcine insulin was bound to the plasma membranes and ninety-five per cent of this binding was inhibited by 1.0 microgram of standard insulin per tube. Four animal insulins inhibited the binding of 125I-insulin while ACTH, glucagon, human growth hormone, and oxytocin were inert. Insulin values in dog pancreatic vein sera obtained during and after glucose loading and measured by the present radioreceptor assay agreed well with immunoreactive insulin. The ratio of IRI to the measurement by radioreceptor assay was 1.09 +/- 0.18 for the same sera.

  18. [Effect of arotinolol on insulin secretion and insulin clearance rate in patients with Graves' disease].

    Science.gov (United States)

    Ohguni, S; Notsu, K; Tanaka, J; Sato, T; Kato, Y

    1993-08-20

    Glucose-induced insulin secretion, 24-h urinary C-peptide (CPR) and euglycemic clamp were examined in five patients with hyperthyroid Graves' disease before and 2 weeks after treatment with arotinolol (20 mg/day, p.o.). Plasma glucose and insulin responses to oral administration of 75 g glucose were not changed by arotinolol treatment. 24-h urinary CPR and basal posthepatic insulin delivery rate (BPIDR) as an indicator of insulin secretion were significantly suppressed by arotinolol. Glucose infusion rate (GIR) as an indicator of insulin sensitivity and glucose clearance rate (GCR) were not influenced by arotinolol therapy. Insulin clearance rate (ICR) was significantly suppressed by arotinolol. These findings suggest that arotinolol inhibits insulin secretion by decreasing ICR but does not attenuate insulin release induced by glucose in hyperthyroid patients, and that insulin sensitivity and GCR are not affected by arotinolol.

  19. High uric acid directly inhibits insulin signalling and induces insulin resistance.

    Science.gov (United States)

    Zhu, Yuzhang; Hu, Yaqiu; Huang, Tianliang; Zhang, Yongneng; Li, Zhi; Luo, Chaohuan; Luo, Yinfeng; Yuan, Huier; Hisatome, Ichiro; Yamamoto, Tetsuya; Cheng, Jidong

    2014-05-16

    Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice. An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signalling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment. Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells. This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro. Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Ghrelin stimulation of growth hormone isoforms: parallel secretion of total and 20-kDa growth hormone and relation to insulin sensitivity in healthy humans.

    Science.gov (United States)

    Tong, Jenny; D'Alessio, David; Ramisch, Juliane; Davis, Harold W; Stambrook, Elizabeth; Tschöp, Matthias H; Bidlingmaier, Martin

    2012-09-01

    The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on glucose metabolism have been debated. To investigate the effect of ghrelin on 20-kDa and total hGH secretion in healthy, nonobese subjects. We also studied associations between basal GH concentration and fasting glucose and insulin as well as between dynamic GH secretion and insulin sensitivity. Synthetic human acyl ghrelin (0.2 or 0.6 nmol/kg · h) or saline was infused in random order in 14 healthy subjects (six males, eight females; age 27.7 ± 6.3 yr; body mass index 22.0 ± 2.7 kg/m(2), mean ± SEM) on 3 separate days. Ghrelin was infused for 45 min to achieve steady-state levels and continued through a 3-h frequently sampled i.v. glucose tolerance test. Insulin sensitivity index was quantified using the minimal model of glucose kinetics. Basal 20-kDa and total GH concentrations were 0.4 ± 0.1 and 2.2 ± 0.4 ng/ml, respectively, with a 20-kDa to total GH ratio of 0.13 ± 0.02. Females had significantly higher baseline GH levels. Ghrelin administration increased 20-kDa and total GH levels in a parallel and dose-dependent fashion, with no significant change in the ratio of the isoforms. Basal 20-kDa and total GH levels were negatively correlated with fasting glucose, insulin, and homeostasis model assessment of insulin resistance. During the frequently sampled iv glucose tolerance test, GH secretion was positively correlated with insulin sensitivity index with saline infusion. Ghrelin dose-dependently increases endogenous 20-kDa and total GH secretion in a parallel fashion in healthy subjects. Both basal and stimulated levels of the different GH isoforms were positively associated with insulin sensitivity in this cohort of healthy men and women.

  1. Insulin, Aging, and the Brain: Mechanisms and Implications

    OpenAIRE

    Akintola, Abimbola A.; van Heemst, Diana

    2015-01-01

    There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into t...

  2. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...... insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.......OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...... of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds...

  4. Algorithms over partially ordered sets

    DEFF Research Database (Denmark)

    Baer, Robert M.; Østerby, Ole

    1969-01-01

    We here study some problems concerned with the computational analysis of finite partially ordered sets. We begin (in § 1) by showing that the matrix representation of a binary relationR may always be taken in triangular form ifR is a partial ordering. We consider (in § 2) the chain structure...... in partially ordered sets, answer the combinatorial question of how many maximal chains might exist in a partially ordered set withn elements, and we give an algorithm for enumerating all maximal chains. We give (in § 3) algorithms which decide whether a partially ordered set is a (lower or upper) semi...

  5. Study on insulin receptor binding characteristics of insulin-IUdR

    International Nuclear Information System (INIS)

    Ou Xiaohong; Kuang Anren; Liang Zhenglu; Peng Xian; Zhong Yuguo

    2002-01-01

    Objective: It has been reported that several kinds of tumors express increased insulin receptors and the molecule of insulin can be internalized in cells and enter the nuclei through the mediation of the insulin receptor. The authors investigated the receptor binding characteristics of insulin-IUdR for the possibility of using insulin as carriers for carcinoma targeted therapy by receptor mediation. Methods: IUdR (idoxuridine) was covalently linked to insulin using the bifunctional reagent succinic acid. The insulin-IUdR conjugate was purified by polyacrylamide agarose gel electrophoresis. The human hepatocellular carcinoma specimens confirmed histologically were obtained from patients at surgery and immediately frozen under -80 degree C. Cell membrane fractions were isolated by sucrose density gradient centrifugation. Competitive displacement of 125 I-insulin with insulin and insulin-IUdR binding to the insulin receptor were carried out. Values of IC 50 and KI were calculated to observe the characteristics of insulin-IUdR binding to the insulin receptor. Results: Insulin-IUdR competed as effectively as insulin with 125 I-insulin for binding to insulin receptors. The values of IC 50 1 and IC 50 2 for insulin-IUdR were (11.50 +- 2.83) nmol/L and (19.35 +- 5.11) nmol/L, respectively; the values of KI1 and KI2 for insulin-IUdR were (11.26 +- 2.65) nmol/L and (19.30 +- 5.02) nmol/L, respectively, while values of IC 50 1 and IC 50 2 for insulin were (5.01 +- 1.24) nmol/L and (17.75 +- 4.86) nmol/L, respectively. The values of KI1 and KI2 for insulin were (4.85 +- 1.12) nmol/L and (17.69 +- 4.81) nmol/L, respectively. Conclusions: Insulin-IUdR could bind with the insulin receptor with high affinity. The result shows that there is a possibility of using insulin as carriers for carcinoma targeted therapy through receptor mediation

  6. A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial: study rationale and design

    Directory of Open Access Journals (Sweden)

    Kristensen Peter

    2012-06-01

    Full Text Available Abstract Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE, multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.

  7. Insulin resistance causes inflammation in adipose tissue.

    Science.gov (United States)

    Shimobayashi, Mitsugu; Albert, Verena; Woelnerhanssen, Bettina; Frei, Irina C; Weissenberger, Diana; Meyer-Gerspach, Anne Christin; Clement, Nicolas; Moes, Suzette; Colombi, Marco; Meier, Jerome A; Swierczynska, Marta M; Jenö, Paul; Beglinger, Christoph; Peterli, Ralph; Hall, Michael N

    2018-03-12

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

  8. Insulin and Breast Cancer Risk

    Science.gov (United States)

    2002-06-01

    hypothesis. Int J Cancer i1995; 62:403-6. 45) Kim YI. Diet, lifestyle and colonrectal cancer : Is hyperinsulinemia the missing link? Nutrition Reviews 1999...with colonrectal cancer , another type of cancer whose etiology has been related to impaired fasting glucose and * hyperinsulinemic insulin resistance...and colonrectal cancer : Is hyperinsulinemia the missing link? Nutrition Reviews 1999; 56:275-9. 46) Kaaks R. Nutrition, hormones, and breast cancer : Is

  9. Preparation and Characterization of Water-Soluble Chitosan Microparticles Loaded with Insulin Using the Polyelectrolyte Complexation Method

    International Nuclear Information System (INIS)

    Wu, S.; Tao, Y.; Zhang, H.; Su, Z.

    2011-01-01

    Polymeric delivery systems based on microparticles have emerged as a promising approach for peroral insulin delivery. The amount of insulin was quantified by the improved Bradford method. It was shown that water-soluble chitosan/insulin/tripolyphosphate (TPP) mass ratio played an important role in microparticles formation. Stable, uniform, and spherical water-soluble chitosan microparticles (WSC-MPs) with high insulin association efficiency were formed at or close to optimized WSC/insulin/TPP mass ratio. WSC-MPs had higher association efficiency in the ph 4.0 and ph 9.7 of TPP solution. The results showed that association efficiency and loading capacity of insulin-loaded WSC-MPs prepared in 0.01 mol/L HCl of insulin were 48.28 ± 0.90% and 9.52 ± 1.34%. The average size of insulin-loaded WSC-MPs was 292 nm. The presented WSC microparticulate system has promising properties towards the development of an oral delivery system for insulin

  10. Preparation and Characterization of Water-Soluble Chitosan Microparticles Loaded with Insulin Using the Polyelectrolyte Complexation Method

    Directory of Open Access Journals (Sweden)

    Sihui Wu

    2011-01-01

    Full Text Available Polymeric delivery systems based on microparticles have emerged as a promising approach for peroral insulin delivery. The amount of insulin was quantified by the improved Bradford method. It was shown that water-soluble chitosan/insulin/tripolyphosphate (TPP mass ratio played an important role in microparticles formation. Stable, uniform, and spherical water-soluble chitosan microparticles (WSC-MPs with high insulin association efficiency were formed at or close to optimized WSC/insulin/TPP mass ratio. WSC-MPs had higher association efficiency in the pH 4.0 and pH 9.7 of TPP solution. The results showed that association efficiency and loading capacity of insulin-loaded WSC-MPs prepared in 0.01 mol/L HCl of insulin were 48.28 ± 0.90% and 9.52 ± 1.34%. The average size of insulin-loaded WSC-MPs was 292 nm. The presented WSC microparticulate system has promising properties towards the development of an oral delivery system for insulin.

  11. Safety of intranasal human insulin: a review.

    Science.gov (United States)

    Schmid, Vera; Kullmann, Stephanie; Gfrörer, Wieland; Hund, Verena; Hallschmid, Manfred; Lipp, Hans-Peter; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas; Heni, Martin

    2018-03-06

    The nasal application of human insulin is frequently used for investigating brain insulin action. It is utilized in studies on the physiological role of insulin in the human brain as well as in therapeutic interventional trials and its effects have been investigated after both acute and long-term administration. This review aimed to assess the safety of intranasal human insulin in human studies and the temporal stability of nasal insulin sprays. The electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were excerpted. Thirty-eight studies on 1092 persons with acute application and 18 studies on 832 persons with treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycemia or severe adverse events were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other adverse events were less commonly reported. There are no reports of subjects who were excluded due to adverse events. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks revealed that it had a chemical stability of up to 57 days. Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns. There is, however, insufficient data to ensure long-term safety of this modality of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment. This article is protected by copyright. All rights reserved.

  12. Insulin-like activity in the retina

    International Nuclear Information System (INIS)

    Das, A.

    1986-01-01

    A number of studies have recently demonstrated that insulin or a homologous peptide may be synthesized outside the pancreas also. The present study was designed to investigate whether insulin-like activity exists in the retina, and if it exists, whether it is due to local synthesis of insulin or a similar peptide in the retina. To determine whether the insulin-like immunoreactivity in retinal glial cells is due to binding and uptake or local synthesis of insulin, a combined approach of immunocytochemistry and in situ DNA-RNA hybridization techniques was used on cultured rat retinal glial cells. Insulin-like immunoreactivity was demonstrated in the cytoplasma of these cells. In situ hybridization studies using labeled rat insulin cDNA indicated that these cells contain the mRNA necessary for de novo synthesis of insulin or a closely homologous peptide. Since human retinal cells have, as yet, not been conveniently grown in culture, an ocular tumor cell line, human Y79 retinoblastoma was used as a model to extend these investigations. The presence of insulin-like immunoreactivity as well as insulin-specific mRNA was demonstrated in this cell line. Light microscopic autoradiography following incubation of isolated rat retinal cells with 125 I-insulin showed the presence of insulin binding sites on the photoreceptors and amarcine cells. On the basis of these observations that rat retina glial cells, including Muller cells are sites of synthesis of insulin or a similar peptide, a model for the pathogenesis of dabetic retinopathy is proposed

  13. Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Caihong Zhu

    Full Text Available Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.

  14. Glucagon-Like Peptide 1 Recruits Muscle Microvasculature and Improves Insulin?s Metabolic Action in the Presence of Insulin Resistance

    OpenAIRE

    Chai, Weidong; Zhang, Xingxing; Barrett, Eugene J.; Liu, Zhenqi

    2014-01-01

    Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature, increases muscle delivery of insulin, and enhances muscle use of glucose, independent of its effect on insulin secretion. To examine whether GLP-1 modulates muscle microvascular and metabolic insulin responses in the setting of insulin resistance, we assessed muscle microvascular blood volume (MBV), flow velocity, and blood flow in control insulin-sensitive rats and rats made insulin-resistant acutely (systemic lipid in...

  15. Reduced Graphene Oxide Modified the Interdigitated Chain Electrode for an Insulin Sensor

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Yagati

    2016-01-01

    Full Text Available Insulin is a key regulator in glucose homeostasis and its deficiency or alternations in the human body causes various types of diabetic disorders. In this paper, we present the development of a reduced graphene oxide (rGO modified interdigitated chain electrode (ICE for direct capacitive detection of insulin. The impedance properties of rGO-ICE were characterized by equivalent circuit modeling. After an electrochemical deposition of rGO on ICE, the electrode was modified with self-assembled monolayers and insulin antibodies in order to achieve insulin binding reactions. The impedance spectra and capacitances were measured with respect to the concentrations of insulin and the capacitance change (ΔC was analyzed to quantify insulin concentration. The antibody immobilized electrode showed an increment of ΔC according to the insulin concentration in human serum ranging from 1 ng/mL to 10 µg/mL. The proposed sensor is feasible for label-free and real-time measuring of the biomarker and for point-of-care diagnosis.

  16. Reduced Graphene Oxide Modified the Interdigitated Chain Electrode for an Insulin Sensor.

    Science.gov (United States)

    Yagati, Ajay Kumar; Park, Jinsoo; Cho, Sungbo

    2016-01-15

    Insulin is a key regulator in glucose homeostasis and its deficiency or alternations in the human body causes various types of diabetic disorders. In this paper, we present the development of a reduced graphene oxide (rGO) modified interdigitated chain electrode (ICE) for direct capacitive detection of insulin. The impedance properties of rGO-ICE were characterized by equivalent circuit modeling. After an electrochemical deposition of rGO on ICE, the electrode was modified with self-assembled monolayers and insulin antibodies in order to achieve insulin binding reactions. The impedance spectra and capacitances were measured with respect to the concentrations of insulin and the capacitance change (ΔC) was analyzed to quantify insulin concentration. The antibody immobilized electrode showed an increment of ΔC according to the insulin concentration in human serum ranging from 1 ng/mL to 10 µg/mL. The proposed sensor is feasible for label-free and real-time measuring of the biomarker and for point-of-care diagnosis.

  17. Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    2016-01-01

    Full Text Available Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice.

  18. Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

    Science.gov (United States)

    Buschard, Karsten; Bracey, Austin W.; McElroy, Daniel L.; Magis, Andrew T.; Osterbye, Thomas; Atkinson, Mark A.; Bailey, Kate M.; Posgai, Amanda L.; Ostrov, David A.

    2016-01-01

    Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice. PMID:26981544

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

    OpenAIRE

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

    2014-01-01

    Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further...

  20. Cancer risk among insulin users

    DEFF Research Database (Denmark)

    But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.

    2017-01-01

    AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005...... follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk...... was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer...

  1. Expectations about insulin therapy, perceived insulin-delivery system social acceptability, and insulin treatment satisfaction contribute to decreases in insulin therapy self-efficacy in patients with type 2 diabetes after 36 weeks insulin therapy.

    Science.gov (United States)

    Hayes, Risa P; Curtis, Bradley; Ilag, Liza; Nelson, David R; Wong, Mayme; Funnell, Martha

    2013-09-01

    Self-efficacy plays a critical role in diabetes self-care. Herein we explore factors contributing to decreased insulin therapy self-efficacy in insulin-naïve patients with type 2 diabetes mellitus (T2DM) initiating and managing insulin therapy over 36 weeks. The study was conducted within an international, randomized clinical trial comparing two insulin therapies administered by insulin pen in patients with T2DM inadequately controlled with oral antihyperglycemic medications. Patients completed the Self-Efficacy about Insulin Therapy Questionnaire (SEITQ) at baseline and endpoint. Patients also completed patient-reported measures assessing expectations about insulin therapy at baseline and perceptions about insulin therapy and insulin-delivery system (IDS) satisfaction at endpoint. Baseline and endpoint SEITQ scores were compared. Using prespecified criteria, patients were classified as having "decreased" or "no change/improved" insulin self-efficacy. Demographic, clinical, and patient-reported variables were entered into a logistic regression model with decreased insulin self-efficacy (yes or no) as the dependent variable. Baseline and endpoint SEITQ data were available for 450 insulin-naïve T2DM patients (mean age 59 years; 53% female; 57% Caucasian; mean baseline HbA1c 9.4%; 80.0 mmol/mol). Insulin therapy self-efficacy improved from baseline to endpoint (74.0 vs 77.5; Psocial acceptability (P=0.004), and more positive expectations of insulin therapy (P<0.0001) were associated with decreased insulin self-efficacy. A candid discussion between clinicians and their insulin-naïve T2DM patients about the benefits and challenges of insulin therapy may prevent unrealistic expectations that could potentially undermine insulin self-efficacy. © 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

  2. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  4. Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle.

    Science.gov (United States)

    Zhang, Liyan; Keung, Wendy; Samokhvalov, Victor; Wang, Wei; Lopaschuk, Gary D

    2010-01-01

    Fatty acids are a major fuel source used to sustain contractile function in heart and oxidative skeletal muscle. To meet the energy demands of these muscles, the uptake and beta-oxidation of fatty acids must be coordinately regulated in order to ensure an adequate, but not excessive, supply for mitochondrial beta-oxidation. However, imbalance between fatty acid uptake and beta-oxidation has the potential to contribute to muscle insulin resistance. The action of insulin is initiated by binding to its receptor and activation of the intrinsic protein tyrosine kinase activity of the receptor, resulting in the initiation of an intracellular signaling cascade that eventually leads to insulin-mediated alterations in a number of cellular processes, including an increase in glucose transport. Accumulation of fatty acids and lipid metabolites (such as long chain acyl CoA, diacylglycerol, triacylglycerol, and/or ceramide) can lead to alterations in this insulin signaling pathway. An imbalance between fatty acid uptake and oxidation is believed to be responsible for this lipid accumulation, and is thought to be a major cause of insulin resistance in obesity and diabetes, due to lipid accumulation and inhibition of one or more steps in the insulin-signaling cascade. As a result, decreasing muscle fatty acid uptake can improve insulin sensitivity. However, the potential role of increasing fatty acid beta-oxidation in the heart or skeletal muscle in order to prevent cytoplasmic lipid accumulation and decrease insulin resistance is controversial. While increased fatty acid beta-oxidation may lower cytoplasmic lipid accumulation, increasing fatty acid beta-oxidation can decrease muscle glucose metabolism, and incomplete fatty acid oxidation has the potential to also contribute to insulin resistance. In this review, we discuss the proposed mechanisms by which alterations in fatty acid uptake and oxidation contribute to insulin resistance, and how targeting fatty acid uptake and

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

    Science.gov (United States)

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

    2015-09-01

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

  6. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Casablanca cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Ahmed Farouqi

    2013-01-01

    Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Casablanca, Morocco. Results: A total of 495 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 231, insulin detemir (n = 151, insulin aspart (n = 19, basal insulin plus insulin aspart (n = 53 and other insulin combinations (n = 41. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.2% and insulin user (mean HbA 1 c: 9.4% groups. After 24 weeks of treatment, both groups showed improvement in HbA 1 c (insulin naïve: −2.3%, insulin users: −1.8%. Major hypoglycaemia was observed in the insulin naïve group after 24 weeks. SADRs were reported in 1.2% of insulin naïve and 2.1% of insulin user groups. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

  7. Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study.

    Science.gov (United States)

    McAuley, Sybil A; Horsburgh, Jodie C; Ward, Glenn M; La Gerche, André; Gooley, Judith L; Jenkins, Alicia J; MacIsaac, Richard J; O'Neal, David N

    2016-08-01

    The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.

  8. Systemisk og lokal allergi over for humant insulin

    DEFF Research Database (Denmark)

    Wittrup, Minna; Pildal, Julie; Rasmussen, Ase Krogh

    2003-01-01

    After introduction of recombinant human insulin, immunological reactions have become rare, but symptomatic immune reactions to insulin still occur. We present four insulin-treated diabetic patients who developed hypersensitivity to insulin or additives to insulin preparations. We show that sympto......After introduction of recombinant human insulin, immunological reactions have become rare, but symptomatic immune reactions to insulin still occur. We present four insulin-treated diabetic patients who developed hypersensitivity to insulin or additives to insulin preparations. We show...... that symptomatic immunological reactions to insulin have not been eliminated by the introduction of recombinant human insulin. Furthermore it demonstrates the importance of skin-biopsy-verified diagnoses and the relevance of differentiation between different types of insulin allergy....

  9. Addition of Zinc Improves the Physical Stability of Insulin in the Primary Emulsification Step of the Poly(lactide-co-glycolide Microsphere Preparation Process

    Directory of Open Access Journals (Sweden)

    Chandrasekar Manoharan

    2015-04-01

    Full Text Available In this study, the effect of zinc on insulin stability during the primary emulsification step of poly(lactide-co-glycolide microspheres preparation by the water-in-oil-in-water (w/o/w double emulsion solvent evaporation technique was evaluated. Insulin was emulsified at homogenization speeds of 5000 and 10,000 rpm. Insulin was extracted from the primary w/o emulsion by a method previously reported from our laboratory and analyzed by comprehensive analytical techniques. The differential scanning calorimetry thermograms of insulin with zinc showed a single peak around 83 °C with calorimetric enthalpy values similar to native insulin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE of extracted insulin showed a single intense band around 6 kDa, demonstrating the preservation of primary structure. High performance liquid chromatography (HPLC analysis revealed that no degradation products were formed during the homogenization process. Insulin aggregates residing at the w/o interfaces were found to be of non-covalent nature. In addition, observation of a single characteristic peak for insulin at m/z 5808 in the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF mass spectrum confirmed the absence of insulin degradation products and covalent dimers. Presence of zinc preserved the secondary structure of insulin as indicated by circular dichroism. In conclusion, these results show that with the addition of zinc, insulin stability can be improved during the primary emulsification step.

  10. Structure-function relationship among Quillaja saponins serving as excipients for nasal and ocular delivery of insulin.

    Science.gov (United States)

    Pillion, D J; Amsden, J A; Kensil, C R; Recchia, J

    1996-05-01

    The purpose of this investigation was to explore the structure-function relationship among naturally occurring Quillaja saponins and derivatives for their ability to stimulate insulin delivery from nosedrops and eyedrops and to test the hypothesis that stimulation of peptide drug delivery was correlated with surfactant strength. Native saponins, including QS-21, were purified from an aqueous extract of Quillaja saponaria bark by adsorption chromatography and HPLC. Native saponins were then deacylated by mild alkaline hydrolysis to form DS-1 and DS-2, derivatives that are smaller and more hydrophilic than their parent compounds. DS-1 was further treated either to reduce an aldehyde residue to form DS-1(R) or to remove the fucose-containing oligosaccharide to form QH-957. Rats receiving eyedrops or nosedrops formulated with insulin, but without any Quillaja saponins, showed no hypoglycemic response. Rats receiving eyedrops or nosedrops formulated with insulin plus saponins showed a dose-dependent hypoglycemic response, with the following rank order: QS-21 > DS-1 > DS-1(R) > DS-2 > QH-957. Surfactant strength was determined by measurement of the critical micellar concentration (cmc) and hemolysis of sheep erythrocytes. The cmc was lowest for the parent saponins QS-21 and QS-18, and increased for the deacylated saponin derivatives DS-1, DS-2, and QH-957; hemolysis of sheep erythrocytes was observed at low concentrations (approximately 0.006 mM) of the parent saponins, QS-21 and QS-18, at intermediate concentrations (0.06-0.08 mM) of DS-1 and DS-2, and at higher concentrations of DS-1(R) (0.45 mM) and QH-957 (1.5 mM). Hence, efficacy as an absorption-enhancing agent was greatest in those saponins with the lowest hemolytic titers and cmc values. However, this relationship was not a strict one, because DS-1, which differs from DS-2 only in the absence of one glucose residue, was significantly more potent than DS-2 in stimulating the absorption of insulin. DS-1 and DS-2

  11. Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein.

    Science.gov (United States)

    Olson, L K; Redmon, J B; Towle, H C; Robertson, R P

    1993-07-01

    Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest. 90:320-325). The mechanism of this seemingly paradoxical phenomenon was examined by transiently transfecting HIT cells with a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5'-regulatory domain of the human insulin gene (INSCAT). Early passages of HIT cells readily expressed INSCAT, whereas late passages of cells chronically cultured in 11.1 mM glucose expressed only 28.7 +/- 2.3% (mean +/- SEM) of the CAT activity expressed in early passages. In contrast, late passages of HIT cells chronically cultured in 0.8 mM glucose retained the ability to express the INSCAT reporter gene to 69.6 +/- 10.0% of the CAT activity observed in early passages. The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter. Formation of this specific protein-DNA complex was preserved in late passages of HIT cells when serially cultured in 0.8 mM glucose. Mutations of the CT motifs caused markedly diminished CAT activity in all passages examined. These data indicate that chronic exposure of the beta cell to high glucose concentrations can paradoxically decrease insulin gene transcription, in part, by altering the ability of a regulatory protein (GSTF) to interact with the insulin gene promoter. This provides a potential mechanism for glucotoxic effects on the beta cell at the level of the insulin gene.

  12. Insulin Regulation of Proteostasis and Clinical Implications.

    Science.gov (United States)

    James, Haleigh A; O'Neill, Brian T; Nair, K Sreekumaran

    2017-08-01

    Maintenance and modification of the cellular proteome are at the core of normal cellular physiology. Although insulin is well known for its control of glucose homeostasis, its critical role in maintaining proteome homeostasis (proteostasis) is less appreciated. Insulin signaling regulates protein synthesis and degradation as well as posttranslational modifications at the tissue level and coordinates proteostasis at the organism level. Here, we review regulation of proteostasis by insulin in postabsorptive, postprandial, and diabetic states. We present the effects of insulin on amino acid flux in skeletal muscle and splanchnic tissues, the regulation of protein quality control, and turnover of mitochondrial protein pools in humans. We also review the current evidence for the mechanistic control of proteostasis by insulin and insulin-like growth factor 1 receptors based on preclinical studies. Finally, we discuss irreversible posttranslational modifications of the proteome in diabetes and how future investigations will provide new insights into mechanisms of diabetic complications. Copyright © 2017. Published by Elsevier Inc.

  13. Associations between depressive symptoms and insulin resistance

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  14. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies...... no differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp. LIMITATIONS: The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production. CONCLUSION: Patients with psoriasis were more insulin resistant compared...... have used suboptimal methodology. The hyperinsulinemic euglycemic clamp remains the gold standard for quantifying whole-body insulin sensitivity. OBJECTIVE: We sought to investigate if normal glucose-tolerant patients with psoriasis exhibit impaired insulin sensitivity. METHODS: Three...

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

    African Journals Online (AJOL)

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

  16. 17 CFR 210.4-01 - Form, order, and terminology.

    Science.gov (United States)

    2010-04-01

    ... prepared according to U.S. Generally Accepted Accounting Principles or International Financial Reporting... accordance with generally accepted accounting principles will be presumed to be misleading or inaccurate... statements may be prepared according to a comprehensive set of accounting principles, other than those...

  17. Order Forms & Price List_2016_Revised_New

    Indian Academy of Sciences (India)

    SR 1

    दिनांक/Date. (वर्तमान अभिदाताओं के लिए: Only for current subscribers). मैं निम्नलिखित पत्रिकाओं के लिए ग्राहक बनना चाहता हूँ। (कृपया उपयुक्त बॉक्स को चिह्नित करें). I would like to subscribe to the following journals. (Please tick mark the appropriate box). Sbeinae aRates.

  18. Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

    Directory of Open Access Journals (Sweden)

    Komariah Komariah

    2017-09-01

    dentate gyrus. This experiment was designed to study the effects of valproic acid administration on the expression of insulin gene in the dentate gyrus of pregnant rats.  This study was carried out at the Laboratory Animal Management Unit (UPHL of Bogor Agricultural University  from May 2015 to December 2016, with eighty four newborn rats from control rats and VA-administered rats at the age of 10, 13, and 16 days of pregnancy. The measurements were done for glucose, insulin, DNA, and RNA concentrations in dentate gyrus and to observe the microscopic condition of the brain at the ages of 4 to 32 weeks with 4 weeks interval.  Rats born form mothers administered by 250 mg valproic acid during pregnancy had higher glucose concentrations (p<0.01 and lower insulin concentrations (p<0.05 in the dentate gyrus. During the post-natal growth phase, rats born from mothers administered with valproic acid had increased glucose concentrations and decreased insulin concentrations (p<0.05. Microscopic observations of the dentate gyrus showed degeneration of nerve cells with no immunoreaction to insulin was seen in dentate gyrus cells. However, the concentrations of DNA, RNA, and the ratio of RNA/DNA in the dentate gyrus cells decreased (p<0.05. The administration of valproic acid to pregnant rats at the age of 10, 13, and 16 days of pregnancy destructs  brain organogenesis of the offsprings which eventually disturbs insulin production in the dentate gyrus indicated by decreased insulin secretion and concentrations.  [MKB. 2017;49(3:156–64] Key words: Dentate gyrus, insulin, organogenesis, valproic acid

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

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance...

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

    DEFF Research Database (Denmark)

    Deshmukh, Atul S

    2016-01-01

    transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle.......Skeletal muscle is the largest tissues in the human body and is considered the primary target for insulin-stimulated glucose disposal. In skeletal muscle, binding of the insulin to insulin receptor (IR) initiates a signaling cascade that results in the translocation of the insulin-sensitive glucose...

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  2. Obesity and Insulin Resistance: Management in Diabetes

    OpenAIRE

    Suhel Ashraff; Muhammad A. Siddiqui; Thomas E. Carline

    2013-01-01

    Obesity today, is a major public health problem across the world. The rapid increase in the incidence of obesity and associated co-morbidities presents a major challenge to health care globally. Insulin resistance is commonly associated with obesity and other life style diseases. However, much uncertainty remains about the mechanism regarding the association between insulin resistance and human disease mainly because of the difficulties of defining insulin resistance in clinical terms and of ...

  3. Insulin Resistance: From Theory To Practice

    Directory of Open Access Journals (Sweden)

    Srinivas Kakkilaya Bevinje

    2006-07-01

    Full Text Available Insulin resistance is at the core of the well recognised metabolic syndrome and possibly many other ailments commonly seen in the modern society. While the quantification of insulin resistance remains a difficult task, the problems associated with it are increasing in epidemic proportions. Need of the hour therefore is to develop concise dietary and pharmacological guidelines for for prevention and management of insulin resistance

  4. How to measure hepatic insulin resistance?

    Science.gov (United States)

    Choukem, S-P; Gautier, J-F

    2008-12-01

    The liver plays a pivotal role in energy metabolism. Under the control of hormones, especially insulin, the liver stores or releases glucose as needed by the body's systems. It is also responsible for an important part of non-esterified fatty-acid and aminoacid metabolism. Assessing hepatic insulin resistance is almost always synonymous with measuring hepatic glucose production (HGP) and calculating indices of hepatic insulin resistance. The most frequently used method to this end is the isotope dilution technique using a tracer. Among tracers, stable isotope-labelled glucose molecules are particularly advantageous over radioactive isotope-labelled glucose and are, therefore, the tracers of choice. The tracer is infused either on its own after an overnight fast to evaluate fasting HGP, or with some among the usual insulin-sensitivity tests to assess HGP suppression by insulin and/or glucose. In a fasting state, HGP is easily calculated whereas, during insulin or glucose infusion, some formula are needed to correct for the non-steady-state condition. The hepatic insulin-resistance index is the product of HGP and the corresponding plasma insulin concentration. Although subject to error, the isotope dilution method nevertheless remains an irreplaceable tool for assessing hepatic insulin resistance in clinical research. From a practical point of view, some easily obtainable indices and clinical or biochemical parameters can serve as surrogates or markers of hepatic insulin resistance in clinical practice. Finally, drugs such as metformin or glitazones can improve hepatic insulin resistance, hence their use in hepatic insulin-resistant states such as type 2 diabetes and non-alcoholic fatty liver disease.

  5. Assessment of insulin sensitivity/resistance

    OpenAIRE

    Gutch, Manish; Kumar, Sukriti; Razi, Syed Mohd; Gupta, Kumar Keshav; Gupta, Abhinav

    2015-01-01

    Insulin resistance is one pretty troublesome entity which very commonly aggravates metabolic syndrome. Many methods and indices are available for the estimation of insulin resistance. It is essential to test and validate their reliability before they can be used as an investigation in patients. At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance and are being used as a reference standard...

  6. Studies on dynamic dissociation constant of 99Mo-insulin complex as anti-diabetic agent

    International Nuclear Information System (INIS)

    Mandal, Swadesh; Nayak, Dalia

    2009-01-01

    The anti-diabetic effects of group VI metals have already been found. This is due to the fact that the oxo-anions of Group VI metals may replace phosphate group in the active centre of enzymes and thus enhancing the insulin signaling. In order to find out an appropriate ligand which may be used as a vehicle of 99 Mo we report the complexation of 99 Mo with insulin protein. The dynamic dissociation constant of the 99 Mo-Insulin complex was studied through dialysis technique against triple distilled water. The K d value of 99 Mo-Insulin complex against triple distilled water is 0.18 h -1 at pH 6.5. The half life of this complex calculated from K d value is 3.85 h against triple distilled water. (author)

  7. Importance of hepatitis C virus-associated insulin resistance: Therapeutic strategies for insulin sensitization

    OpenAIRE

    Kawaguchi, Takumi; Sata, Michio

    2010-01-01

    Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection. Generally, persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases. However, these complications are not major causes of death in patients with HCV-associated insulin resistance. Indeed, insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection. ...

  8. Altered insulin distribution and metabolism in type I diabetics assessed by [123I]insulin scanning

    International Nuclear Information System (INIS)

    Hachiya, H.L.; Treves, S.T.; Kahn, C.R.; Sodoyez, J.C.; Sodoyez-Goffaux, F.

    1987-01-01

    Scintigraphic scanning with [ 123 I]insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of [ 123 I]insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of [ 123 I]insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of [ 123 I]insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of [ 123 I]insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of [ 123 I]insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of [ 123 I]insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of [123I]insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001)

  9. Update on insulin treatment for dogs and cats: insulin dosing pens and more

    OpenAIRE

    Thompson A; Lathan P; Fleeman L

    2015-01-01

    Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin c...

  10. Update on insulin treatment for dogs and cats: insulin dosing pens and more

    Directory of Open Access Journals (Sweden)

    Thompson A

    2015-04-01

    Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

  11. Insulin or insulin-like studies on unicellular organisms: a review

    OpenAIRE

    Souza,Alzira Martins Ferreira de; López,Jorge A.

    2004-01-01

    This paper presents a review of studies about insulin and insulin-like substances in prokaryotes, eukaryotes and fungi have been published over the last two decades, constituting an updating of our previous review (1988) which included references to invertebrate insulin or insulin-like substances both in uni- and pluricellular Monera, Protoctista, Fungii and Animal species. This present article reviews experiments and evidence obtained using modern techniques in the understanding of molecule ...

  12. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  13. [Alteration of insulin secretion in the elderly].

    Science.gov (United States)

    Aizawa, Toru

    2006-01-01

    Aging per se is associated with reduced insulin secretion, which is an important contributing factor for pandemic of diabetes worldwide. Although underlying mechanism for it is not fully elucidated, a combination of reduced beta cell mass and impairment of insulin granule handing in the cell is most likely which may be due to age-related mitochondrial dysfunction and/or dysregulation of transcriptional factors. For effective prevention of diabetes in the elderly population, restoration of beta cell function is desired. Meanwhile, identification of insulin-deficient elderly patients with diabetes and an earlier institution of insulin therapy for them are recommended for improvement of treatment outcome.

  14. Hepatoselectivity and the evolution of insulin.

    Science.gov (United States)

    Herring, R; Jones, R H; Russell-Jones, D L

    2014-01-01

    In spite of major developments in insulin production, purification, pharmaceutical formulation and methods of delivery, problems remain both in the day to day management of insulin-treated diabetes and with regard to its long-term complications. The risks of hypoglycaemia and weight gain are major concerns particularly for the patient, and the persistence of microvascular and premature macrovascular complications as the main causes of morbidity and mortality in both type 1 and type 2 diabetes is a constant reminder that our therapeutic and management strategies are inadequate. One clear and striking difference between currently available insulin treatments and normal physiology is the relative difference in exposure to insulin of the liver versus peripheral tissues. Hepatoselective insulin analogues have the potential to restore the normal hepatic to peripheral gradient in insulin action. Here, we discuss the possible therapeutic potential that such analogues may have over currently available insulin preparations. These benefits could include a lower risk of hypoglycaemia, less weight gain and a potential reduction in microvascular and macrovascular complications. We explore the evolution of insulin with hepatoselectivity in mind and possible strategies to create hepatoselective insulins. © 2013 John Wiley & Sons Ltd.

  15. Diminished hepatic insulin removal in obesity

    International Nuclear Information System (INIS)

    Cano, I.; Salvador, J.; Rodriguez, R.; Arraiza, M.C.; Goena, M.; Barberia, J.J.; Moncada, E.

    1986-01-01

    Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out

  16. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole-body...... was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The Prazosin treatment did not affect...

  17. Chitosan nanofibers for transbuccal insulin delivery.

    Science.gov (United States)

    Lancina, Michael G; Shankar, Roopa Kanakatti; Yang, Hu

    2017-05-01

    In this work, they aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Chitosan was electrospun into nanofibers using poly(ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Taken together, the work demonstrates that chitosan-based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1252-1259, 2017. © 2017 Wiley Periodicals, Inc.

  18. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    M. E. Hansen

    2014-01-01

    Full Text Available Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.

  19. Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

    International Nuclear Information System (INIS)

    Levy, J.R.; Olefsky, J.M.

    1988-01-01

    The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 0 C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 0 C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation

  20. Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

    Directory of Open Access Journals (Sweden)

    Chih-Ting Su

    2016-11-01

    Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

  1. Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients

    NARCIS (Netherlands)

    Potter van Loon, B. J.; Radder, J. K.; Froelich, M.; Krans, H. Michiel J.; Zwinderman, A. H.; Meinders, A. E.

    1992-01-01

    Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral

  2. Will long acting insulin analogs influence the use of insulin pump therapy in type 1 diabetes?

    NARCIS (Netherlands)

    DeVries, J. Hans

    2005-01-01

    Insulin pump therapy enjoys a steadily growing number of users and is associated with an approximately 0.5% lower A1c as compared to flexible insulin injection therapy in type 1 diabetes patients. An important question is whether superiority of insulin pump therapy persists in the era of rapid

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Tectonics: The meaning of form

    DEFF Research Database (Denmark)

    Christiansen, Karl; Brandt, Per Aage

    Tectonics – The meaning of form deals with one of the core topics of architecture: the relationship between form and content. In the world of architecture, form is not only made from brick, glass and wood. Form means something. When a material is processed with sufficient technical skill and insi......Tectonics – The meaning of form deals with one of the core topics of architecture: the relationship between form and content. In the world of architecture, form is not only made from brick, glass and wood. Form means something. When a material is processed with sufficient technical skill...... perspectives. You can read the chapters in any order you like – from the beginning, end or the middle. There is no correct order. The project is methodologically inductive: the more essays you read, the broader your knowledge of tectonics get....

  7. Insulin and Weight Gain: Keep the Pounds Off

    Science.gov (United States)

    Insulin and weight gain: Keep the pounds off Insulin and weight gain often go hand in hand, but weight control is possible. If you need insulin therapy, here's how to minimize — or avoid — weight ...

  8. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...

  9. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

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

  10. Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review.

    Science.gov (United States)

    Hagenmeyer, Ernst-Günther; Koltermann, Katharina C; Dippel, Franz-Werner; Schädlich, Peter K

    2011-10-06

    Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses

  11. Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

    Directory of Open Access Journals (Sweden)

    Dippel Franz-Werner

    2011-10-01

    Full Text Available Abstract Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH the long-acting analogue insulin glargine (GLA is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science and DAHTA (Deutsche Agentur für Health Technology Assessment, and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP. Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER. The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI. Conclusions The incremental cost-utility-ratios (ICER show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK is adopted

  12. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O

    2003-01-01

    AIMS: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin...... infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...

  13. Insulin Signaling in Type 2 Diabetes

    Science.gov (United States)

    Brännmark, Cecilia; Nyman, Elin; Fagerholm, Siri; Bergenholm, Linnéa; Ekstrand, Eva-Maria; Cedersund, Gunnar; Strålfors, Peter

    2013-01-01

    Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems level mechanistic understanding of insulin resistance, using systems wide and internally consistent data from human adipocytes. Based on quantitative steady-state and dynamic time course data on signaling intermediaries, normally and in diabetes, we developed a dynamic mathematical model of insulin signaling. The model structure and parameters are identical in the normal and diabetic states of the model, except for three parameters that change in diabetes: (i) reduced concentration of insulin receptor, (ii) reduced concentration of insulin-regulated glucose transporter GLUT4, and (iii) changed feedback from mammalian target of rapamycin in complex with raptor (mTORC1). Modeling reveals that at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, which explains reduced sensitivity and signal strength throughout the signaling network. Model simulations with inhibition of mTORC1 are comparable with experimental data on inhibition of mTORC1 using rapamycin in human adipocytes. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling, both at the cellular level and, using a multilevel model, at the whole body level. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis. PMID:23400783

  14. Development and validation of the insulin treatment appraisal scale (ITAS in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Skovlund Søren E

    2007-12-01

    Full Text Available Abstract Background Timely initiation of insulin therapy in type 2 diabetes is important to achieve metabolic control but can be hindered by negative perceptions of patients regarding insulin treatment. To assess the appraisal of insulin therapy of persons with type 2 diabetes, we developed the insulin treatment appraisal scale (ITAS and tested its reliability and validity in insulin treated type 2 diabetes patients. Methods A sample of 282 patients with type 2 diabetes form the United States (US completed the ITAS, the WHO-5 Well-being index (WHO-5 and the Problem Areas in Diabetes (PAID Survey. Exploratory factor analysis (EFA, internal consistency (Cronbach's alpha and item-total correlations were determined to test the reliability of the instrument. Concurrent validity was examined by calculating Pearson correlation coefficients between the different measures. Discriminant validity was examined by comparing ITAS scores of insulin naive and insulin using patients. Results EFA suggested a two-factor structure, separating positively worded and negatively worded items. Cronbach's alpha was 0.90 for the negative appraisal scale and 0.68 for the positive appraisal scale. Yet, Cronbach's alpha of the total 20-item scale was 0.89, suggesting high homogeneity and allowing for calculation of an overall score. Item-total correlations were in the range of 0.46–0.74 for the negative and 0.34 – 0.53 for the positive appraisal scale. The item pertaining to weight gain, as part of the negative appraisal subscale, showed low communality and deserves further testing. Concurrent validity was confirmed with low to moderate correlations in the expected direction between ITAS and WHO-5 and PAID. Discriminant validity was confirmed by the fact that patients using insulin had significantly less negative appraisals than insulin naive patients. Conclusion The ITAS is a brief, psychometrically sound instrument that can be used in insulin naive and insulin

  15. A Review of the Security of Insulin Pump Infusion Systems

    OpenAIRE

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

    2011-01-01

    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, secur...

  16. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women.

    Science.gov (United States)

    Phillips, Gerald B; Jing, Tianyi; Heymsfield, Steven B

    2008-06-01

    Insulin resistance, obesity, and a sex hormone alteration have each been suggested as the underlying link for the constellation of risk factors for myocardial infarction (MI) commonly referred to as the metabolic syndrome or the insulin resistance syndrome. In an attempt to identify in women which of these variables is the most likely link, insulin, adiposity variables, sex hormones, and risk factors for MI were measured and their relationships analyzed statistically in 58 premenopausal and 20 postmenopausal healthy women. On controlling for age, visceral adipose tissue (VAT) correlated more strongly with risk factors for MI, insulin, and free testosterone (FT) than did total adipose tissue or subcutaneous adipose tissue. VAT, therefore, was used as the adiposity variable for further data analysis. Waist circumference was a better surrogate of VAT than was waist-hip ratio, which was a poor surrogate of VAT. VAT correlated positively with insulin, FT, triglyceride, and glucose, and negatively with high-density lipoprotein and sex hormone-binding globulin. On controlling for age, FT and insulin correlated with risk factors for MI and with each other, but on controlling for age and VAT, all of their correlations lost statistical significance except for FT-triglyceride and FT-insulin in the postmenopausal women. In conclusion, VAT accumulation in women, independently of other measures of adiposity, may largely explain the correlations of insulin, obesity, and sex hormones with risk factors for MI and may be the immediate underlying factor that links risk factors for MI to form the metabolic syndrome. Insulin resistance, which has been generally accepted to be the underlying factor, may be a component of the syndrome rather than its underlying link. We hypothesize that in women FT may effect preferential VAT accumulation and induce insulin resistance directly, as well as via VAT accumulation, so that a sex hormone alteration may underlie VAT accumulation and thus

  17. Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial.

    Science.gov (United States)

    Asemi, Z; Samimi, M; Tabassi, Z; Naghibi Rad, M; Rahimi Foroushani, A; Khorammian, H; Esmaillzadeh, A

    2013-01-01

    Owing to excess body weight and increased secretion of inflammatory cytokines primarily during the third trimester, pregnancy is associated with elevated insulin resistance. To our knowledge, no report is available indicating the effects of probiotic yoghurt consumption on serum insulin levels in pregnant women. This study was designed to determine the effects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women. In this randomized controlled clinical trial, 70 primigravida pregnant women with singleton pregnancy at their third trimester were participated. We randomly assigned participants to consume 200 g per day of conventional (n=33) or the probiotic group (n=37) for 9 weeks. The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus, enriched with probiotic culture of two strains of lactobacilli (Lactobacillus acidophilus LA5) and bifidobacteria (Bifidobacterium animalis BB12) with a total of min 1 × 10⁷ colony-forming units. Fasting blood samples were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance score. Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score, significant differences were found comparing changes in these variables between probiotic and conventional yogurts (changes from baseline in serum insulin levels: +1.2±1.2 vs +5.0±1.1 μIU/ml, respectively, P=0.02; and in HOMA-IR score: -0.2±0.3 vs 0.7±0.2, respectively, P=0.01). It is concluded that in contrast to conventional yogurt, daily consumption of probiotic yogurt for 9 weeks maintains serum insulin levels and might help pregnant women prevent developing insulin resistance.

  18. Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available We previously showed the impairment of insulin-regulated gene expression in the primary hepatocytes from Zucker fatty (ZF rats, and its association with alterations of hepatic glucose and lipid metabolism. However, the molecular mechanism is unknown. A preliminary experiment shows that the expression level of protein kinase C ζ (PKCζ, a member of atypical PKC family, is higher in the liver and hepatocytes of ZF rats than that of Zucker lean (ZL rats. Herein, we intend to investigate the roles of atypical protein kinase C in the regulation of hepatic gene expression. The insulin-regulated hepatic gene expression was evaluated in ZL primary hepatocytes treated with atypical PKC recombinant adenoviruses. Recombinant adenovirus-mediated overexpression of PKCζ, or the other atypical PKC member PKCι/λ, alters the basal and impairs the insulin-regulated expressions of glucokinase, sterol regulatory element-binding protein 1c, the cytosolic form of phosphoenolpyruvate carboxykinase, the catalytic subunit of glucose 6-phosphatase, and insulin like growth factor-binding protein 1 in ZL primary hepatocytes. PKCζ or PKCι/λ overexpression also reduces the protein level of insulin receptor substrate 1, and the insulin-induced phosphorylation of AKT at Ser473 and Thr308. Additionally, PKCι/λ overexpression impairs the insulin-induced Prckz expression, indicating the crosstalk between PKCζ and PKCι/λ. We conclude that the PKCζ expression is elevated in hepatocytes of insulin resistant ZF rats. Overexpressions of aPKCs in primary hepatocytes impair insulin signal transduction, and in turn, the down-stream insulin-regulated gene expression. These data suggest that elevation of aPKC expression may contribute to the hepatic insulin resistance at gene expression level.

  19. PEDF expression is inhibited by insulin treatment in adipose tissue via suppressing 11β-HSD1.

    Directory of Open Access Journals (Sweden)

    Yinli Zhou

    Full Text Available Early intensive insulin therapy improves insulin sensitivity in type 2 diabetic patients; while the underlying mechanism remains largely unknown. Pigment epithelium-derived factor (PEDF, an anti-angiogenic factor, is believed to be involved in the pathogenesis of insulin resistance. Here, we hypothesize that PEDF might be down regulated by insulin and then lead to the improved insulin resistance in type 2 diabetic patients during insulin therapy. We addressed this issue by investigating insulin regulation of PEDF expression in diabetic conditions. The results showed that serum PEDF was reduced by 15% in newly diagnosed type 2 diabetic patients after insulin therapy. In adipose tissue of diabetic Sprague-Dawley rats, PEDF expression was associated with TNF-α elevation and it could be decreased both in serum and in adipose tissue by insulin treatment. In adipocytes, PEDF was induced by TNF-α through activation of NF-κB. The response was inhibited by knockdown and enhanced by over expression of NF-κB p65. However, PEDF expression was indirectly, not directly, induced by NF-κB which promoted 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1 expression in adipocytes. 11β-HSD1 is likely to stimulate PEDF expression through production of active form of glucocorticoids as dexamethasone induced PEDF expression in adipose tissue. Insulin inhibited PEDF by down-regulating 11β-HSD1 expression. The results suggest that PEDF activity is induced by inflammation and decreased by insulin through targeting 11β-HSD1/glucocorticoid pathway in adipose tissue of diabetic patients.

  20. Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

    Science.gov (United States)

    Stanley, Molly; Macauley, Shannon L.

    2016-01-01

    Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942