Ability Of Glucose Research Articles

O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function

Although insulin mediated glucose uptake in skeletal muscle is a major mechanism ensuring glucose disposal in humans, glucose effectiveness, i.e., the ability of glucose itself to stimulate its own uptake independent of insulin, accounts for roughly half of the glucose disposed during an oral glucose tolerance test. Both insulin dependent and insulin independent skeletal muscle glucose uptake are however reduced in individuals with diabetes. We here show that AMPK activator O304 stimulates insulin independent glucose uptake and utilization in skeletal muscle and heart in vivo, while preventing glycogen accumulation. Combined glucose uptake and utilization requires an increased metabolic demand and we show that O304 acts as a mitochondrial uncoupler, i.e., generates a metabolic demand. O304 averts gene expression changes associated with metabolic inflexibility in skeletal muscle and heart of diabetic mice and reverts diabetic cardiomyopathy. In Type 2 diabetes, insulin resistance elicits compensatory insulin hypersecretion, provoking β-cell stress and eventually compensatory failure. In db/db mice O304 preserves β-cell function by preventing decline in insulin secretion, β-cell mass, and pancreatic insulin content. Thus, as a dual AMPK activator and mitochondrial uncoupler O304 mitigates two central defects of T2D; impaired glucose uptake/utilization and β-cell failure, which today lack effective treatment.

English

BACKGROUND Diabetic ketoacidosis (DKA) is a life-threatening condition of diabetes that is characterized by hyperglycaemia, ketoacidosis, and ketonuria. It happens when glucose's ability to enter cells for use as metabolic fuel is blocked by absolute or relative insulin deficiency. This causes liver to divide fat into ketones as a source of fuel. The purpose of the study was to assess the knowledge regarding prevention of signs and symptoms of diabetic ketoacidosis among diabetes patients in selected hospitals of Wardha district. METHODS A descriptive study was undertaken among 60 purposively selected patients of diabetes with diabetic ketoacidosis in Wardha district. Data was collected by using structured knowledge questionnaire during the month of May 2020. RESULTS The level of awareness among diabetes patients on how to avoid diabetic ketoacidosis was measured. The findings of study show that 49 (80 %) people had poor level of knowledge score and 11 (20 %) people had average level of knowledge score. Mean score was 4.38 ± 2.48 with mean percentage 24.35 ± 13.80. The association of knowledge score with educational status of diabetes patients from selected hospital. The tabulated ‘F’ values were 2.76 (df = 3, 56) which is much less than the calculated ‘F’ i.e., 8.73 at 5 % level of significance. Also, the calculated ‘P’=0.0001 which was much less than the acceptable level of significance i.e., ‘P’=0.05. Hence, it is interpreted that educational status of diabetes patients is statistically associated with their knowledge score. CONCLUSIONS Most patients with diabetes are poorly aware of the preventive measures of diabetic ketoacidosis. This study revealed several preventive gaps relating to an appropriate prevention strategy and acute diabetes complications. This research concluded that most patients with diabetes had insufficient knowledge of the signs and symptoms of diabetic ketoacidosis and its management. KEY WORDS Knowledge, Prevention, Sign, Symptoms, Diabetic Ketoacidosis, Diabetes Patients

Управление и поддержка принятия решений в системе персонализированной инсулинотерапии

Insulin therapy automation is an actual research line in the glycemic control of diabetes mellitus type 1 patients. Development of closed-loop systems and methods will allow blood glucose maintaining in the physiological range. The work proposes the personalized insulin therapy system considered as a closed-loop control system based on feedback and external disturbances compensation principles. Automatic feedback-based glycemic control includes proportional reg-ulation of basal insulin infusion rate in relation to optimized thresholds inside the target range. To achieve bidirectional glycemic regulation the author proposes model predictive control for calculation of not only optimal profile of bolus infusion but also recommended corrective dose of carbohydrates. Besides, the comparative analysis of trends in measured and predicted profiles of blood glucose allows detecting and compensation of its unpredicted deviations. In silico testing of developed algorithms on nine virtual adults for 72 hours shows an ability for glucose maintaining in the target range for whole system operation time.

An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling.

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min–1 (standard error – 0.00078 min–1) in the ND population to 0.011 min–1 (standard error – 0.00045 min–1) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein.

Rapid quantitative detection of glucose using biological sensor system as combined with electrochemical data treatment

ABSTRACT In this paper, glucose quantitative detection by biological sensor and electrochemical capacitance data treatment was studied. The taste cells were fixed on carbon screen-printed electrode. Electrochemical capacitance responses of cell-based sensor to sucrose in different concentrations and related mixtures were measured. Glucose quantitative analysis results demonstrated that the proposed method had quantitative determination abilities toward glucose and related mixtures. The signal-to-noise ratio index presented qualitative discrimination abilities to different glucose mixtures. Negative control results indicated that the receptor-free cells showed no perception ability for glucose. The proposed method is promising in sugar rapid detection.

367-OR: High-Fat and Fructose Feeding Severely Impairs Hepatic Glucose Effectiveness

Diets high in fat and fructose (HFFD) disrupt glucose metabolism. The aim of this study was to determine if HFFD impairs hepatic glucose effectiveness (i.e., the ability of glucose per se to stimulate net hepatic glucose uptake [NHGU] and/or to suppress glucose production [Ra]). In overnight fasted dogs fed either a chow diet or HFFD for 1 month, somatostatin, 3-3H-glucose, and basal hepatic portal vein infusions of insulin and glucagon were given. After a basal sampling period, these infusions continued for 4h while glucose was infused to create a 3-fold rise in plasma glucose. Since hepatic glucose uptake is also stimulated by a negative arterial to portal vein glucose gradient, such as occurs with glucose ingestion, glucose was either all infused into a peripheral vein (Chow-PeG, n=6; HFFD-PeG, n=6), or a portion was also given into the portal vein (4 mg/kg/min; Chow-PoG, n=5; HFFD-PoG, n=5). There were no differences in plasma insulin, glucagon, arterial glucose, or hepatic glucose load between groups. In response to hyperglycemia, the liver switched from making (basal period) to storing (last h) glucose in the chow fed groups (1.1±0.1 to -2.0±0.5* mg/kg/min in Chow-PeG, and 1.3±0.1 to -3.0±0.9* in Chow-PoG; a negative rate indicates uptake). Conversely, HFFD markedly reduced liver glucose effectiveness. In fact, with HFFD the liver did not take up glucose in response to hyperglycemia whether the portal signal was absent (1.4±0.1 to 1.0±0.3 in HFFD-PeG) or present (1.6±0.3 to 0.0±0.3* in HFFD-PoG). Thus, in the Chow vs. HFFD groups, the impact of hyperglycemia on overall net hepatic glucose balance was 3.1±0.5 vs. 0.4±0.4* (13% of normal) in the absence of portal glucose delivery and 4.3±0.9 vs. 1.6±0.5* (37% of normal) in its presence. Hyperglycemia suppressed Ra by 75±12 vs. 22±6%* (last h) in Chow vs. HFFD-PeG, respectively, and by 81±14 vs. 34±7%* in Chow vs. HFFD-PoG. In summary, HFFD induced a severe impairment in hepatic glucose effectiveness but did not affect the liver’s response to the portal glucose signal. (*P<0.05). Disclosure D.S. Edgerton: None. G. Kraft: None. B. Farmer: None. M. Scott: None. M.S. Smith: None. A.D. Cherrington: Advisory Panel; Self; Biocon, Fractyl Laboratories, Inc., Metavention, Sekkei Bio, Sensulin, LLC., vTv Therapeutics, Zafgen, Inc. Consultant; Self; Thetis Pharmaceuticals LLC. Research Support; Self; Diasome Pharmaceuticals, Inc. Other Relationship; Self; Abvance Therapeutics, Novo Nordisk Inc. Funding National Institutes of Health (R01DK18243)

Features of the glucose influence on the heart activity and the changes in the potentials of the stomach and the intestines at the heart insufficiency conditions

In acute rat experiments (thiopental sodium narcosis), it is established that introducing a 5 % glucose solution into the stomach lowers a frequency of heart rates (HR) and an amplitude of potentials of smooth muscles of the stomach and simultaneously raises doubtfully and shortly the potentials of sooth muscles (PSM) of the colon. Food additives used in the glutamate sodium, benzoate, tartrazine complex do not influence HR, but as before, reduces PSM of the stomach, and in the thick gut precise exciting or brake responses are marked. In the preliminarily developed heart insufficiency conditions, the glucose infusion into the stomach does not change HR. At the same time, the action of glucose, as well as of food additives, still results in reliable reactions of the stomach and the thick gut. Important is the present work information on the ability of glucose and food additives to modulate the heart activity estimated through the indicators of modification of electrocardiogram teeth. As appeared, the infusion of the specified irritants in the stomach of rats in control and heart insufficiency is accompanied by precise enough changes in such indicators as the RST duration, the amplitude and duration of the Т-wave, i. e. the prognostic attributes of the opportunity of occurrence of heart аrrhythmia, fibrillations.

Conserved roles of glucose in suppressing reactive oxygen species-induced cell death and animal survival.

Carbohydrate overconsumption increases blood glucose levels, which contributes to the development of various diseases including obesity and diabetes. It is generally believed that high glucose metabolism increases cellular reactive oxygen species (ROS) levels, damages insulin-secreting cells and leads to age-associated diabetic phenotypes. Here we find that in contrast, high glucose suppresses ROS production induced by paraquat in both mammalian cells and the round worm C. elegans. The role of glucose in suppressing ROS is further supported by glucose’s ability to alleviate paraquat’s toxicity on C. elegans development. Consistently, we find that the ROS-regulated transcription factor SKN-1 is inactivated by glucose. As a result, the ROS/SKN-1-dependent lifespan extension observed in paraquat-treated animals, mitochondrial respiration mutant isp-1 and germline-less mutant glp-1 are all suppressed by glucose. Our study reveals an unprecedented interaction of glucose with ROS, which could have significant impact on our current understanding of glucose- and ROS-related diseases.

On the Effects of UV Radiation on the Release Ability of Glucose Embedded in Hydroxypropyl Cellulose Films

ABSTRACTNew drug delivery systems based on hydroxypropyl cellulose (HPC) and different percents of glucose were prepared and characterized to check their suitability as UV resistant patches. The spectral absorption properties of the HPC and HPC-glucose blends before and after UV irradiation were analyzed. The surface polarity and hydrophilicity were correlated with the morphology of the films and analyzed with respect to the UV exposure time and the embedded amount of glucose. The effects of UV radiation on in vitro evaluation of glucose release from the HPC films are reported. The mechanism involved in the drug release process, evaluated using the Korsmeyer-Peppas equation, was dependent on the introduced amount of glucose and less on the UV exposure time. A more polar, smoother, and less dense surface releases the glucose over larger periods of time, making the system with lower percents of glucose more adequate for the pursued purpose.

The forgotten role of glucose effectiveness in the regulation of glucose tolerance.

Glucose effectiveness (SG) is the ability of glucose per se to stimulate its own uptake and to suppress its own production under basal/constant insulin concentrations. In an individual, glucose tolerance is a function of insulin secretion, insulin action and SG. Under conditions of declining insulin secretion and action (e.g. type 2 diabetes), the degree of SG assumes increasing significance in determining the level of glucose tolerance both in fasted and postprandial states. Although the importance of SG has been recognized for years, mechanisms that contribute to SG are poorly understood. Research data on modulation of SG and its impact in glucose intolerance is limited. In this review, we will focus on the role of SG in the regulation of glucose tolerance, its evaluation, and potential advantages of therapies that can enhance glucose-induced stimulation of glucose uptake and suppression of its own production in conditions of impaired insulin secretion and action.

ChemInform Abstract: Water-Promoted Claisen Sigmatropic Rearrangement Using Glyco-Organic Substrates. Chiral Auxiliary-Mediated Induction.

Abstract The Claisen sigmatropic rearrangement with glyco-organic substrates is greatly accelerated in water. Moreover, the ability of glucose to function as a chiral auxiliary is illustrated in the preparation of 4-pentene-1,3-diol , obtained for the first time in pure enantiomeric form.

Hepatic Insulin Sensitivity Assessed by Integrated Model of Hepatic and Peripheral Glucose Regulation

The integrated model of hepatic and peripheral glucose metabolism incorporates a model for liver glucose metabolism into the two-compartment minimal model framework to describe endogenous glucose kinetics during a labeled intravenous glucose tolerance test (IVGTT). This model also provides a parametric description of endogenous glucose production (EGP). The present study extended the theoretical potential of the model by defining hepatic glucose effectiveness (hS(G)(2)) as the ability of glucose per se to inhibit EGP and hepatic insulin sensitivity (hS(1)(2)) as the ability of insulin to enhance glucose suppression of EGP. As a retrospective data base review of our previous study, we re-analyzed time courses of exogenous and endogenous glucose concentration during [6,6-(2)H(2)]glucose-labeled IVGTT (0.3 g/kg glucose), performed in 11 exercise-trained and 12 age-matched sedentary subjects. Model parameters of the two-compartment minimal model and of liver glucose metabolism were simultaneously identified to assess insulin sensitivity specific to stimulate glucose uptake (S(1)(2*)) and that specific to inhibit EGP (hS(1)(2)). The abilities of glucose per se to stimulate its own uptake (S(G)(2*)) and to inhibit EGP (hS(G)(2)) were also estimated. Parameters of the integrated model were identified in all the subjects. Hepatic insulin sensitivity consisted of about one-third of total insulin sensitivity (S(1)(2*) + hS(1)(2)). Compared with the sedentary subjects, S(1)(2*), hS(1)(2), hS(G)(2) of the trained subjects were greater. Because insulin resistance in liver and peripheral tissue may play a differential role in the pathogenesis of diabetes, this analysis can serve as a simple one-step approach to obtain metabolic indexes specific to EGP suppression and stimulating glucose uptake.

Inhibiting gluconeogenesis prevents fatty acid-induced increases in endogenous glucose production

Glucose effectiveness, the ability of glucose per se to suppress endogenous glucose production (EGP), is lost in type 2 diabetes mellitus (T2DM). Free fatty acids (FFA) may contribute to this loss of glucose effectiveness in T2DM by increasing gluconeogenesis (GNG) and impairing the response to hyperglycemia. Thus, we first examined the effects of increasing plasma FFA levels for 3, 6, or 16 h on glucose effectiveness in nondiabetic subjects. Under fixed hormonal conditions, hyperglycemia suppressed EGP by 61% in nondiabetic subjects. Raising FFA levels with Liposyn infusion for > or =3 h reduced the normal suppressive effect of glucose by one-half. Second, we hypothesized that inhibiting GNG would prevent the negative impact of FFA on glucose effectiveness. Raising plasma FFA levels increased gluconeogenesis by approximately 52% during euglycemia and blunted the suppression of EGP by hyperglycemia. Infusion of ethanol rapidly inhibited GNG and doubled the suppression of EGP by hyperglycemia, thereby restoring glucose effectiveness. In conclusion, elevated FFA levels rapidly increased GNG and impaired hepatic glucose effectiveness in nondiabetic subjects. Inhibiting GNG could have therapeutic potential in restoring the regulation of glucose production in type 2 diabetes mellitus.

Regulating Glucose

Increased extracellular glucose stimulates firing of a subset of proopiomelanocortin (POMC)-containing neurons in the hypothalamus through a mechanism thought to depend, like insulin secretion in pancreatic β cells, on the adenosine 5′-triphosphate (ATP)-dependent closure of ATP-sensitive potassium (K ATP ) channels in the plasma membrane. Parton et al . generated transgenic mice (POMC-mut-Kir6.2 mice) that expressed a mutant K ATP Kir6.2 subunit under the transcriptional control of the POMC promoter, so that relatively ATP-insensitive K ATP channels were selectively expressed in hypothalamic POMC neurons (and in the pituitary). Although the body weight of POMC-mut-Kir6.2 mice was normal, glucose homeostasis was impaired so that they showed an exaggerated increase in blood glucose after intraperitoneal glucose injection. Whereas the firing rate of about half the POMC neurons in wild-type mice was stimulated by physiologically relevant increases in glucose concentration, only 1 of 27 POMC neurons in POMC-mut-Kir6.2 mice was glucose-sensitive. Glucose stimulated release of α-melanocyte–stimulating hormone (α-MSH) from hypothalamic slices from wild-type, but not POMC-mut-Kir6.2, mice. Moreover, it failed to stimulate the release of α-MSH from hypothalamic slices of wild-type mice fed a high-fat diet, and its effect on the firing rate of their POMC neurons was severely attenuated. Expression of the mRNA encoding uncoupling protein 2 (UCP2, a mitochondrial protein that decreases ATP production from glucose) was increased in the hypothalami of obese mice, and pharmacological inhibition of UCP with genipin stimulated firing in glucose-sensitive POMC neurons from wild-type mice. Genipin had little effect on POMC neuronal firing in POMC-mut-Kir6.2 mice, but it restored glucose-dependent release of hypothalamic α-MSH in mice fed a high-fat diet. Furthermore, although mice lacking UCP2 became obese when fed a high-fat diet, the ability of glucose to elicit release of their hypothalamic α-MSH was intact. Thus, the authors conclude that glucose sensing by hypothalamic POMC neurons is implicated in systemic glucose homeostasis, a sensitivity that is lost through a mechanism involving UCP2 in obese mice fed a high-fat diet. They further note that these findings may be pertinent to the pathogenesis of type 2 diabetes. L. E. Parton, C. P. Ye, R. Coppari, P. J. Enriori, B. Choi, C.-Y. Zhang, C. Xu, C. R. Vianna, N. Balthasar, C. E. Lee, J. K. Elmquist, M. A. Cowley, B. B. Lowell, Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449 , 228-232 (2007). [PubMed]

Extrapancreatic Effects of GIP and GLP-1

Incretin-based therapy promises to be a useful adjunct in the treatment of diabetes. Glucagon-like peptide-1 (GLP1) and, to a lesser extent, glucose-dependent insulinotropic polypeptide (GIP) are potent stimulators of insulin secretion, and consequently have significant effects on the regulation of the glucose metabolism. What has been less clear, however, is whether these hormones exert direct effects on glucose metabolism independent of their effect on pancreatic insulin and glucagon release. Glucose effectiveness and insulin action (the ability of glucose and insulin respectively to stimulate glucose uptake and suppress glucose release) have been reported by some investigators, but not others, to improve during incretin infusion. The purpose of this review is briefly to examine some of the numerous conflicting reports in the literature as to the presence or otherwise of extrapancreatic incretin effects. In addition, we will briefly discuss the gastrointestinal effects of incretins. These effects may be of considerable importance in the treatment of postprandial hyperglycemia although they are not, strictly speaking, the result of a direct incretin effect on glucose metabolism.

Denitrification associated N loss in mangrove soil

Despite the well-known mechanism of N loss through denitrification in wetland, little information is available for mangrove soil. The aim of this study is to quantify N loss via denitrification in mangrove soil, to clarify factors affecting denitrification and to evaluate the role of plants in the mechanism of nitrification–denitrification in mangrove soil. The N loss from mangrove soil was 76%, possibly 55% through denitrification, measured using a 15N tracer technique. The N loss was reduced to 45% when a nitrification inhibitor, N-serve, was added. Planting reduced the N loss from mangrove soil more than the nitrification inhibitor. The combination of planting and applicasion of nitrification inhibitor completely prevented N loss from mangrove soil. Denitrification in fresh soil samples from a mangrove forest declined markedly from the surface to the sub-surface soil. Available C limited denitrification. The ability of glucose to induce denitrification declined with soil depth, suggesting a decline in the denitrifier population with depth. Significant reduction in N loss from mangrove soil after adding nitrification inhibitor indicates that nitrification is the key factor in N loss of mangrove soil. As there was no significant difference in denitrification between rhizosphere and non-rhizosphere soil, the cause of N loss in the mangrove soil may occur primarily in the surface soil rather than in the rhizosphere soil.

Glucose effectiveness: measurement in diabetic and nondiabetic humans.

It is well established that under the conditions of daily living, insulin secretion and insulin action determine glucose tolerance in nondiabetic humans both in the post-absorptive and post-prandial states. However, in recent years, glucose effectiveness (i.e., the ability of glucose per se to stimulate its own uptake and to suppress its own release) has also been shown to influence glucose tolerance in both diabetic and nondiabetic individuals. In states of deficient insulin action, e.g., in individuals with type 2 diabetes, glucose effectiveness assumes a greater role in determining glucose tolerance both during fasting and post-prandial conditions. A mathematical model (Minimal Model) of glucose turnover has been applied to estimate glucose effectiveness in both diabetic and nondiabetic individuals. Several investigators have demonstrated reduced glucose effectiveness in people with type 2 diabetes mellitus. However, measurements of glucose effectiveness by the traditional single compartment minimal model approach have been fraught with errors when compared to model independent estimates, especially in the diabetic population. This has led investigators to modify the parameters of the model with the incorporation of glucose tracers and the use of two-compartment model of glucose kinetics. Although this has made the indices of glucose effectiveness more robust, proper validation experiments are necessary before widespread application of these methods.

Prandial glucose effectiveness and fasting gluconeogenesis in insulin-resistant first-degree relatives of patients with type 2 diabetes.

Impaired glucose effectiveness (i.e., a diminished ability of glucose per se to facilitate its own metabolism), increased gluconeogenesis, and endogenous glucose release are, together with insulin resistance and beta-cell abnormalities, established features of type 2 diabetes. To explore aspects of the pathophysiology behind type 2 diabetes, we assessed in a group of healthy people prone to develop type 2 diabetes (n = 23), namely first-degree relatives of type 2 diabetic patients (FDR), 1) endogenous glucose release and fasting gluconeogenesis measured using the 2H2O technique and 2) glucose effectiveness. The FDR group was insulin resistant when compared with an age-, sex-, and BMI-matched control group without a family history of type 2 diabetes (n = 14) (M value, clamp: 6.07 +/- 0.48 vs. 8.06 +/- 0.69 mg x kg(-1) lean body weight (lbw) x min(-1); P = 0.02). Fasting rates of gluconeogenesis (1.28 +/- 0.06 vs. 1.41 +/- 0.07 mg x kg(-1) lbw x min(-1); FDR vs. control subjects, P = 0.18) did not differ in the two groups and accounted for 53 +/- 2 and 60 +/- 3% of total endogenous glucose release. Glucose effectiveness was examined using a combined somatostatin and insulin infusion (0.17 vs. 0.14 mU x kg(-1) x min(-1), FDR vs. control subjects), the latter replacing serum insulin at near baseline levels. In addition, a 360-min labeled glucose infusion was given to simulate a prandial glucose profile. After glucose infusion, the integrated plasma glucose response above baseline (1,817 +/- 94 vs. 1,789 +/- 141 mmol/l per 6 h), the ability of glucose to simulate its own uptake (1.50 +/- 0.13 vs. 1.32 +/- 0.16 ml x kg(-1) lbw x min(-1)), and the ability of glucose per se to suppress endogenous glucose release did not differ between the FDR and control group. In conclusion, in contrast to overt type 2 diabetic patients, healthy people at high risk of developing type 2 diabetes are characterized by normal glucose effectiveness at near-basal insulinemia and normal fasting rates of gluconeogenesis.

Pubertal adolescent male-female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model.

Most studies of insulin sensitivity in puberty have been cross-sectional and have not been able to longitudinally address changes that might occur. In addition, these studies were unable to separate out glucose's ability to stimulate its own disposal (glucose effectiveness, S(G)) from insulin sensitivity (S(I)) or to separate the hepatic and peripheral effects of insulin. To address these problems, we used the frequently sampled i.v. glucose tolerance test with [6,6]D2 glucose to study S(G)* and S(I)* in 24 children (Tanner stage 1-3) at 6-mo intervals over an 18-mo period. Mean overnight GH and fasting GH binding protein (GHBP), IGF-1, and leptin levels were also measured. S(G)* did not differ between the sexes or Tanner stages. S(I)* did not differ between Tanner stages for either sex and was higher in boys than in girls. Hepatic insulin resistance did not differ between sexes or Tanner stages. S(G)* was not related to any of the other variables measured. S(I)* was negatively related to BMI, GHBP, IGF1, and leptin. These results demonstrate that insulin sensitivity is greater in prepubertal and early pubertal boys than in girls and is primarily determined by body mass effects.

Glucose-induced insulin mRNA accumulation is impaired in islets from neonatal streptozotocin-treated rats.

According to the "glucose toxicity" hypothesis, hyperglycemia contributes to defective beta-cell function in type 2, non-insulin-dependent diabetes mellitus. This concept is supported by substantial data in rodent models of diabetes. However, the ability of glucose to stimulate the accumulation of insulin mRNA, a critical feature of normal beta-cell physiology, has not been investigated in in vivo models with chronic hyperglycemia. The aim of this study was to determine whether glucose-induced insulin mRNA accumulation is impaired in the neonatal streptozotocin-treated rat (n0-STZ rat), a model of non-obese, non-insulin-dependent diabetes mellitus. Islets of Langerhans isolated from n0-STZ and control rats were cultured for 24 h in the presence of 2.8 or 16.7 mmol/l glucose, and insulin mRNA levels were measured by Northern analysis. Insulin mRNA levels were increased more than twofold by glucose in control islets. In contrast, no significant effect of glucose was found on insulin mRNA levels in n0-STZ islets. We conclude that insulin gene regulation by glucose is impaired in n0-STZ rat islets.