GK糖尿病大鼠生物学特性观察

目的了解2型糖尿病模型GK大鼠生长曲线、主要脏器重量、糖代谢等生物学特性,评价GK大鼠葡萄糖刺激的胰岛素分泌能力。方法采用51只雄性GK大鼠及15只年龄性别匹配的Wistar大鼠作为研究对象。测定13周龄GK、Wistar大鼠空腹血糖、23周龄GK大鼠空腹及随机血糖。随访GK及Wistar大鼠生长曲线,34～46周龄期间血糖、糖化血红蛋白。46周龄时行腹腔葡萄糖耐量实验（IPGTT）,计算相关参数评价β细胞葡萄糖刺激的胰岛素分泌能力;之后处死大鼠,脏器称重。比较GK及Wistar大鼠间上述各指标差异。结果13周龄GK大鼠空腹血糖4．74±0．41mmol／L,对照Wistar大鼠1．85±0．44mmol／L（P〈0．001）。23周龄GK大鼠空腹血糖7．88±1．96mmol／L,随机血糖9．91±3．52～13．46±4．13mmol／L。7～20及34～45周龄期间GK大鼠体重高于对照Wistar大鼠（P〈0．05）,46周龄时无显著性差异。34～45周龄期间GK大鼠空腹血糖、进食后血糖、HbAlc均高于对照Wistar大鼠（P〈0．05）。IPGTT曲线下面积分析示GK大鼠胰岛素曲线下面积（AUCi）、葡萄糖曲线下面积（AUCg）高于对照Wistar大鼠,胰岛素与葡萄糖曲线下面积比值（AUCi／AUCg）低于对照Wistar大鼠,差异均有显著性（P〈0．05）。GK大鼠肾脏重量高于对照Wistar大鼠（P〈0．05）,余主要脏器重量差异无显著性。结论GK大鼠空腹血糖、进食后血糖、HbAlc水平升高,葡萄糖刺激的胰岛素分泌能力（GSIS）减退,葡萄糖刺激后胰岛素分泌早期相消失,晚期相代偿性增加,具有2型糖尿病特点;体重、血糖等生物学特性稳定。     

Basal and stimulated hyperinsulinemia in obesity: relationship to adipose-cell size.

In 17 non-selected, non-hyperlipoproteinemic subjects without overt diabetes both adipose tissue biopsy and an oral glucose tolerance test (50 g) were performed. All persons were weight-stable at the time of investigation. A significant correlation between fasting insulin concentration and mean adipocyte volume was observed, whereas no correlation existed between ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated basal insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte volumes, the difference in insulin levels was still demonstrable. This study underlines the importance of adipose-cell enlargement regulating basal and stimulated insulin output.     

Hyperinsulinemia in obesity: significance of adipose tissue cell size

Adipose tissue biopsy and an oral glucose tolerance test (OGTT) (50 g) were performed in 17 non-hyperlipoproteinemic subjects without overt diabetes mellitus. All the persons were weight stable at the time of investigation. A significant correlation between fasting insulin concentration and the mean adipocyte size was observed, whereas no correlation was noted between the ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte sizes, the difference in insulin levels was still demonstrable. The importance of adipose cell enlargement regulating basal and stimulated insulin output is underlined.     

Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function

Exercise improves glucose tolerance in obese rodent models and humans; however, effects with respect to mechanisms of beta-cell compensation remain unexplained. We examined exercise's effects during the progression of hyperglycemia in male Zucker diabetic fatty (ZDF) rats until 19 wk of age. At 6 wk old, rats were assigned to 1) basal--euthanized for baseline values; 2) exercise--swam individually for 1 h/day, 5 days/wk; and 3) controls (n = 8-10/group). Exercise (13 wk) resulted in maintenance of fasted hyperinsulinemia and prevented increases in fed and fasted glucose (P < 0.05) compared with sham-exercised and sedentary controls (P < 0.05). Beta-cell function calculations indicate prolonged beta-cell adaptation in exercised animals alone. During an intraperitoneal glucose tolerance test (IPGTT), exercised rats had lower 2-h glucose (P < 0.05) vs. controls. Area-under-the-curve analyses from baseline for IPGTT glucose and insulin indicate improved glucose tolerance with exercise was associated with increased insulin production and/or secretion. Beta-cell mass increased in exercised vs. basal animals; however, mass expansion was absent at 19 wk in controls (P < 0.05). Hypertrophy and replication contributed to expansion of beta-cell mass; exercised animals had increased beta-cell size and bromodeoxyuridine incorporation rates vs. controls (P < 0.05). The relative area of GLUT2 and protein kinase B was significantly elevated in exercised vs. sedentary controls (P < 0.05). Last, we show formation of ubiquitinated protein aggregates, a response to cellular/oxidative stress, occurred in nonexercised 19 wk-old ZDF rats but not in lean, 6 wk-old basal, or exercised rats. In conclusion, improved beta-cell compensation through increased beta-cell function and mass occurs in exercised but not sedentary ZDF rats and may be in part responsible for improved glucoregulation.     

Pathogenesis of hyperglycemia in genetically obese-hyperglycemic rats, Wistar fatty: presence of hepatic insulin resistance

The present studies were designed to clarify the contribution of the liver to the development of hyperglycemia in Wistar fatty rats. The hepatic activities of insulin-inducible enzymes involved in glycolysis (glucokinase; GK and pyruvate kinase) and lipogenesis (glucose-6-phosphate dehydrogenase), were higher in fatty rats than in lean rats at 4 and 8 weeks of age because of the higher insulin levels in the former. Thereafter, the GK activities of fatty rats decreased slightly in spite of severe hyperinsulinemia, and did not differ from those of lean rats. In addition, fatty rats had higher levels of insulin-suppressible gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1, 6-diphosphatase. These findings indicate that the hepatic enzymes of fatty rats are resistant to insulin. This postulation was supported by the fact that the hepatic enzyme activities of fatty rats showed a lower response to changes in plasma insulin levels produced by fasting and refeeding. The G6Pase/GK ratio, which indicates net glucose handling in the liver, increased in fatty rats and decreased in lean rats with advancing age, suggesting that hepatic glucose production in fatty rats becomes dominant with advancing age. The changes in hepatic glycolytic intermediates supported this suggestion; the glycolytic steps both from glucose to glucose-6-phosphate and from phospho-enolpyruvate to pyruvate in fatty rats were accelerated at 5 weeks of age, but suppressed at 12 weeks of age. These results indicate that insulin resistance in the hepatic enzyme regulation may contribute to the development of hyperglycemia in Wistar fatty rats.     

Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats

Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.     

Assessing Impaired Glucose Tolerance and Insulin Resistance in Polycystic Ovarian Syndrome with A Muffin Test: An Alternative to the Glucose Tolerance Test

ObjectiveTo determine the sensitivity of a high-glucose load in a meal as an alternative to the standard oral glucose tolerance test (OGTT) in detecting impaired glucose tolerance and insulin resistance in women with polycystic ovarian syndrome (PCOS) and the relationship of body composition to insulin resistance in the PCOS cohort.MethodsIn this prospective, single-center study, women with PCOS who were being followed up as outpatients were recruited. The study was performed between November 2007 and March 2008. All participants underwent OGTT before study enrollment. Participants were given a meal including carbohydrates, fat, and protein. Glucose and insulin levels were measured every 30 minutes for 2 hours after completing the meal. Body composition was measured by dual-energy x-ray absorptiometry.ResultsThirteen of the 15 participants completed the meal tolerance test and the body composition study. Four of 13 participants (31%) had abnormal glucose tolerance with the meal test compared with 2 of 8 participants (25%) who completed the OGTT. Those who had insulin resistance on OGTT were detected with the meal test. The 2-hour insulin levels following the meal were 38% higher than with the OGTT. Of 10 participants with insulin resistance, 9 had a total body fat mass greater than the 90th percentile, whereas 1 of 3 participants (33%) with normal body composition was insulin resistant.ConclusionAdministration of oral glucose load via a meal is an effective alternative to the OGTT in diagnosing impaired glucose tolerance and insulin resistance and may be more sensitive, without the adverse effects of the oral glucose load in the OGTT. PCOS is an independent risk factor for impaired glucose tolerance and insulin resistance, regardless of body composition. (Endocr Pract. 2010;16:810-817)     

Endogenous opiate modulators of insulin secretion in the obese

The effects of endogenous opiates on insulin response to oral glucose load were studied in obese subjects and in lean healthy volunteers. None of these having a family diabetes. After 3 days on an 1,800 cal./m2, 40% carbohydrate diet all subjects underwent two standard 75 g oral glucose tolerance tests (OGTT), one of which was accompanied by an i. v. administration of 10 mg of, an antagonist of opiates, the naloxone. In one group of obese impaired oral glucose tolerance test occurred. All obese, but not the lean healthy volunteers, showed: 1) increased basal plasma insulin levels, 2) higher insulin response to OGTT, 3) a decrease in insulin response to OGTT after naloxone administration, with significant differences at 60 min (p less than 0.01) and 90 min (p less than 0.025). In none of the subjects significant differences were observed in blood glucose levels after OGTT plus naloxone administration. These data suggest that increased endogenous opiates may affect insulin response to glucose in obese with impaired or normal oral glucose tolerance test. At present there seems to be no satisfactory explanation for unchanged blood glucose levels during OGTT with and without naloxone despite a decrease in insulin secretion in the obese patients.     

Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance

Glucose tolerance declines with age, resulting in a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Hyperglycemia per se can lead to impaired beta-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related beta-cell dysfunction in older people (65 +/- 8 yr) with IGT treated with the alpha-glucosidase inhibitor acarbose (n = 14) or placebo (n = 13) for 6 wk in a randomized, double-blind study. Baseline and posttreatment studies included 1) an oral glucose tolerance test (OGTT), 2) 1-h postprandial glucose monitoring, 3) a frequently sampled intravenous glucose tolerance test (insulin sensitivity, or S(I)), and 4) glucose ramp clamp (insulin secretion rates, or ISR), in which a variable glucose infusion increases plasma glucose from 5 to 10 mM. The treatment groups had similar baseline body mass index; fasting, 2-h OGTT, and 1-h postprandial glucose levels; and S(I). In these carefully matched older people with IGT, both fasting (5.7 +/- 0.2 vs. 6.3 +/- 0.2 mM, P = 0.002) and 1-h postprandial glucose levels (6.9 +/- 0.3 vs. 8.2 +/- 0.4 mM, P = 0.02) were significantly lower in the acarbose than in the placebo group. Despite this reduction of chronic hyperglycemia in the acarbose vs. placebo group, measures of insulin secretion (ISR area under the curve: 728 +/- 55 vs. 835 +/- 81 pmol/kg, P = 0.9) and acute insulin response to intravenous glucose (329 +/- 67 vs. 301 +/- 54 pM, P = 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse beta-cell dysfunction in older people with IGT.     

Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance

Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C-peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced.     

Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.     

Short-term exercise training early in life restores deficits in pancreatic β-cell mass associated with growth restriction in adult male rats

Fetal growth restriction is associated with reduced pancreatic β-cell mass, contributing to impaired glucose tolerance and diabetes. Exercise training increases β-cell mass in animals with diabetes and has long-lasting metabolic benefits in rodents and humans. We studied the effect of exercise training on islet and β-cell morphology and plasma insulin and glucose, following an intraperitoneal glucose tolerance test (IPGTT) in juvenile and adult male Wistar-Kyoto rats born small. Bilateral uterine vessel ligation performed on day 18 of pregnancy resulted in Restricted offspring born small compared with sham-operated Controls and also sham-operated Reduced litter offspring that had their litter size reduced to five pups at birth. Restricted, Control, and Reduced litter offspring remained sedentary or underwent treadmill running from 5 to 9 or 20 to 24 wk of age. Early life exercise increased relative islet surface area and β-cell mass across all groups at 9 wk, partially restoring the 60-68% deficit (P < 0.05) in Restricted offspring. Remarkably, despite no further exercise training after 9 wk, β-cell mass was restored in Restricted at 24 wk, while sedentary littermates retained a 45% deficit (P = 0.05) in relative β-cell mass. Later exercise training also restored Restricted β-cell mass to Control levels. In conclusion, early life exercise training in rats born small restored β-cell mass in adulthood and may have beneficial consequences for later metabolic health and disease.     

Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice

Because biotin treatment may lower blood glucose in insulin-dependent diabetes, we chose to study such an effect in non-insulin dependent diabetes. Twenty-six diabetic KK mice, moderately hyperglycemic and insulin resistant, were treated for 10 weeks: 9 animals with 2 mg of biotin/Kg, 8 with 4 mg of biotin/Kg, and 9 with saline (controls). Blood glucose levels, oral glucose tolerance, insulin response to oral glucose, and blood glucose decrease in response to insulin were quantitated. Compared to controls, biotin treatment lowered post-prandial glucose levels, and improved tolerance to glucose and insulin resistance. Serum immunoreactive insulin levels in biotin-treated mice were like the controls.     

Insulin and glucagon relationships during aging in rats.

Oral glucose tolerance tests were performed under pentobarbital anesthesia in 43 male Wistar rats 2 to 18 months of age in order to determine if insulin and glucagon secretion are altered with aging. Although any linear correlation was not demonstrated between aging and blood glucose, plasma insulin or glucagon levels, post-glucose levels of blood glucose were significantly suppressed and those of plasma glucagon were significantly elevated at 4 to 6 months of age. No significant difference was found between young (2 months of age) and aged rats (12 to 14 and 17 to 18 months of age) in either blood glucose or plasma insulin levels during oral glucose load. On the other hand, post-glucose plasma glucagon levels of the aged rats were significantly higher than those of the young ones. Furthermore, comparisons of various kinds of indices among the different age groups, such as insulinogenic index, insulin/glucagon and so forth during oral glucose tolerance tests also indicate the significant alteration of glucagon secretion during aging process. It is concluded from the present data that glucose tolerance does not apparently deteriorate during aging process in rats but that glucagon responses to oral glucose administration are elevated with aging.     

Insulin and glucagon secretion and the insulin sensitivity of peripheric organs of colony-bred sand rats fed with pellet diet after weaning.

Colony-bred sand rats were fed with rat pellet chow in restricted quantities or ad libitum for 8--10 or 28--31 weeks after weaning. The changes of glucose metabolism were characterized by an intraperitoneal glucose tolerance test. The daily food intake and the average weight gain differed only in the first 5--7 weeks of pellet nutrition. In the impaired glucose tolerance tests of all sand rats the high basal plasma IRI levels were not significantly increased by the grossly enhanced blood glucose concentrations. The insulin secretion of either acutely incubated or for 8 days cultivated isolated pancreatic islets, however, was stimulated already by low (1.7 and 5 mM) glucose concentrations in all diet groups. Otherwise the glucagon secretion of isolated islets was not suppressed by high glucose concentrations. No changes of insulin or glucagon contents of islets were found in the different diet groups. The adipocytes of all animals revealed a complete ineffectiveness of insulin on the glucose utilization to CO2 and triglycerides. The basal glucose conversion to CO2 and glycogen in skeletal muscle and the stimulatory potency of insulin was low and not distinctly different in all groups. In liver glycogen and triglyceride contents as well as gluconeogenic enzyme activities were not influenced by feeding of different quantities of pellet diet at the investigated time points. The time course of the metabolic and clinical alterations demonstrates that the peripheral organs become insensitive to insulin in the first weeks after weaning.     

Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats

F344/DuCrj rats are genetically deficient in dipeptidyl peptidase IV (DPPIV). This enzyme degrades glucagon-like peptide-1 (GLP-1), which induces glucose-dependent insulin secretion. Glucose tolerance of F344/DuCrj rats is improved as a result of enhanced insulin release induced by high levels of plasma GLP-1. In this study, we fed F344/DuCrj rats and DPPIV-positive F344/Jcl rats, aged five weeks, on a high-fat (HF) diet to examine the effect of DPPIV deficiency on food intake and insulin resistance. F344/Jcl rats gained significantly more body weight and consumed significantly more food than F344/DuCrj rats from Week 4 on either control or HF diet. Glucose excursion in the oral glucose tolerance test (OGTT) was improved in F344/DuCrj rats fed on the control or HF diet at all times examined, compared with F344/Jcl rats. Homeostasis model assessment (HOMA) insulin resistance values of F344/DuCrj and F344/Jcl rats fed on HF diet were higher than those of animals fed on control diet up to Week 6. However, HOMA insulin resistance values of F344/DuCrj rats fed on HF diet became significantly lower than those of F344/Jcl rats on HF diet during Weeks 8-10. The area under the insulin curve in the OGTT at Week 10 showed that the insulin resistance of HF-diet-fed F344/DuCrj rats was greatly ameliorated. Plasma active GLP-1 concentrations of F344/DuCrj rats in the fed state were significantly higher than those of F344/Jcl rats. These observations suggest that DPPIV deficiency results in improved glucose tolerance and ameliorated insulin resistance owing to enhanced insulin release and inhibition of food intake as a result of high active GLP-1 levels.     

Impaired glucose priming of insulin secretion from perfused pancreas in aged female rats.

Effects of age and glucose levels on insulin secretion and synthesis were studied in the perfused pancreas of young (2-month-old) and older (10-month-old) female Wistar rats. Insulin secretion induced by 16.7 mM glucose showed a triphasic pattern: an early spike and fall (first phase, 0-6 min), followed by a sustained gradual increase (second phase, 7-120 min) and a gradual decreased release thereafter (third phase, 121-360 min) during the perfusion period of 360 min. First and second phase insulin secretion, but not third phase, were lower in older rats than in young rats. Insulin synthesis in old rat pancreas perfused with 16.7 nM glucose for 360 min was much greater than that of young rats. Second phase insulin secretion was restored to comparable levels by 28 mM glucose in older rats. Repeated pulses of 28 mM glucose potentiated subsequent insulin secretion in young rats, but not in older rats. These findings provide further evidence that sensitivity to glucose in pancreatic B cells is altered by aging.     

Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats

Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin–eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function.     

Taurine supplementation modulates glucose homeostasis and islet function

Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity.