Effects of 5-campestenone (24-methylcholest-5-en-3-one) on the type 2 diabetes mellitus model animal C57BL/KsJ-db/db mice.

We examined the therapeutic effects of dietary exposure to 5-campestenone (24-methylcholest-5-en-3-one), an enone derivative of campesterol, in C57BL/KsJ-db/db mice, which are an animal model of obese type 2 diabetes. Blood glucose levels of db/db mice linearly increased from 270 to 720 mg/dl in 10 weeks, an approximately 7-fold difference from the levels of db/+m mice. The 0.3 % dietary exposure to 5-campestenone caused a marked reduction in blood glucose levels of 330 mg/dl after 10 weeks of feeding with a concomitant inhibition of glucose excretion in urine. Only slight efficacy was observed with 0.1 % dietary exposure to this chemical in db/db mice. Significant decreases of plasma triglyceride and plasma free fatty acid were also observed in db/db mice at a 0.3 % dose. However, feed efficiency and body-weight gain in db/db mice was improved by 5-campestenone. No obvious anomaly due to consumption of 5-campestenone was detected by necropsy or clinical observation.     

Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats

Increasing evidence supports a negative role of glycogen synthase kinase-3 (GSK-3) in regulation of skeletal muscle glucose transport. We assessed the effects of chronic treatment of insulin-resistant, prediabetic obese Zucker (fa/fa) rats with a highly selective GSK-3 inhibitor (CT118637) on glucose tolerance, whole body insulin sensitivity, plasma lipids, skeletal muscle insulin signaling, and in vitro skeletal muscle glucose transport activity. Obese Zucker rats were treated with either vehicle or CT118637 (30 mg/kg body wt) twice per day for 10 days. Fasting plasma insulin and free fatty acid levels were reduced by 14 and 23% (P < 0.05), respectively, in GSK-3 inhibitor-treated animals compared with vehicle-treated controls. The glucose response during an oral glucose tolerance test was reduced by 18% (P < 0.05), and whole body insulin sensitivity was increased by 28% (P < 0.05). In vivo insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (50%) and IRS-1-associated phosphatidylinositol-3' kinase (79%) relative to fasting plasma insulin levels were significantly elevated (P < 0.05) in plantaris muscles of GSK-3 inhibitor-treated animals. Whereas basal glucose transport in isolated soleus and epitrochlearis muscles was unaffected by chronic GSK-3 treatments, insulin stimulation of glucose transport above basal was significantly enhanced (32-60%, P < 0.05). In summary, chronic treatment of insulin-resistant, prediabetic obese Zucker rats with a specific GSK-3 inhibitor enhances oral glucose tolerance and whole body insulin sensitivity and is associated with an amelioration of dyslipidemia and an improvement in IRS-1-dependent insulin signaling in skeletal muscle. These results provide further evidence that selective targeting of GSK-3 in muscle may be an effective intervention for the treatment of obesity-associated insulin resistance.     

Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice

This study examines whether anti-diabetic effects of genistein and daidzein are mediated by hepatic glucose and lipid regulating enzyme activities in type 2 diabetic animals. Male C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The blood glucose and HbA(1c) levels were significantly lower in the genistein and daidzein groups than in the control group, while glucose tolerance only was significantly improved in the genistein-supplemented group. The plasma insulin and C-peptide levels did not differ significantly between groups, yet the glucagon level was lower in the genistein and daidzein groups compared to that in the control db/db or db/+ group. The genistein and daidzein supplements increased the insulin/glucagon ratio in the type 2 diabetic animals. While the hepatic glucokinase activity was significantly lower in the db/db control group, the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly higher in the control group compared to the db/+ group. Interestingly, these hepatic glucose metabolizing enzyme activities were reversed by the genistein and daidzein supplementation in db/db mice compared to the control group. The hepatic fatty acid synthase, beta-oxidation and carnitine palmitoyltransferase activities were all significantly lower in the genistein and daidzein groups than in the control group. The genistein and daidzein supplements also improved the plasma total cholesterol, triglyceride, HDL-cholesterol/total cholesterol, free fatty acid and hepatic triglyceride concentrations in the db/db mice. These results suggest that genistein and daidzein exert anti-diabetic effect in type 2 diabetic conditions by enhancing the glucose and lipid metabolism.     

Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 ± 11 vs. 110 ± 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 ± 13 vs. 25 ± 3 μIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.     

Chronic glucose-lowering effects of rosiglitazone and bis(ethylmaltolato)oxovanadium(IV) in ZDF rats

The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 micromol/kg) were selected to produce a glucose-lowering effect in 30% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg.day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60% of fatty animals as compared with 30% for BEOV and 10% for ROS alone. The age-dependent decrease in plasma insulin levels associated with beta-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.     

西格列汀对2 型糖尿病患者微量白蛋白尿影响的研究

目的:研究西格列汀对2型糖尿病患者微量白蛋白尿的影响,分析其可能机制和临床应用价值。方法:选取160例伴微量白蛋白尿的2型糖尿病患者,随机分为西格列汀组和其他药物组,各80例。比较两组患者治疗前和治疗3个月后血糖水平、尿微量白蛋白、超敏C反应蛋白及血浆还原型谷胱甘肽水平。结果:经3个月治疗,两组患者空腹血糖、餐后2 h血糖、Hb A1c均较治疗前下降,但差异无明显统计学意义(P0.05);西格列汀治疗组患者尿微量白蛋白和血浆Hs-CRP水平明显下降,血浆还原型谷胱甘肽水平明显升高,与其他口服药物治疗组相比差异具有统计学意义(P0.05)。结论:西格列汀可能通过改善机体炎症状态,降低氧化和应激水平等机制降低2型糖尿病患者的尿微量白蛋白水平。     

Inhibition of lipolysis does not affect insulin sensitivity to glucose uptake in the mourning dove

Birds have much higher plasma glucose and fatty acid levels compared to mammals. In addition, they are resistant to insulin-induced decreases in blood glucose. Recent studies have demonstrated that decreasing fatty acid utilization alleviates insulin resistance in mammals, thereby decreasing plasma glucose levels. This has yet to be examined in birds. In the present study, the levels of glucose and beta-hydroxybutyrate (BOHB), a major ketone body and indicator of fatty acid utilization, were measured after the administration of chicken insulin, acipimox (an anti-lipolytic agent), or insulin and acipimox in mourning doves (Zenaidura macroura). Insulin significantly decreased whole blood glucose levels (19%), but had no effect on BOHB concentrations. In contrast, acipimox decreased blood BOHB levels by 41%, but had no effect on whole blood glucose. In addition to changes in blood composition, levels of glucose uptake by various tissues were measured after the individual and combined administration of insulin and acipimox. Under basal conditions, the uptake of glucose appeared to be greatest in the kidney followed by the brain and skeletal muscle with negligible uptake by heart, liver and adipose tissues. Acipimox significantly decreased glucose uptake by brain (58% in cortex and 55% in cerebellum). No significant effect of acipimox was observed in other tissues. In summary, the acute inhibition of lipolysis had no effect on glucose uptake in the presence or absence of insulin. This suggests that free fatty acids alone may not be contributing to insulin resistance in birds.     

Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects

Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis. Oxidative stress caused by triglycerides and free fatty acids is known to cause insulin resistance and hyperinsulinemia. On the other hand, insulin resistance may increase homocysteine levels. Since obesity is associated with insulin resistance and hyperinsulinemia, we aimed to study the possible association of homocysteine with hyperinsulinemia in obese subjects. 20 obese male subjects (body mass index >29), aged 33--55 (mean 45 years old) were studied. A fasting blood sample was obtained for the study and the subjects undertook an oral glucose tolerance test with samples taken at 1 and 2 h after glucose. Subjects were divided in two groups according to the fasting insulin levels, < 9 &mgr;U/ml or normoinsulinemic (group 1) and >9 &mgr;U/ml or hyperinsulinemic (group 2). Glucose, insulin, homocysteine, folate, B(12,) total cholesterol, HDL-cholesterol and triglycerides levels were determined in fasting blood samples. In oral glucose tolerance test, glucose, insulin and homocysteine levels were measured. Hyperinsulinemic obese subjects (group 2) had higher levels of insulin and glucose at 1 h and 2 h postglucose, compared with group 1. Fasting total homocysteine and triglyceride levels were also increased in this group, whereas folate and B(12) levels were similar in both groups. Fasting homocysteine significantly correlated with fasting insulin (r = 0.6, p <0.01). Homocysteine levels slightly but significantly decreased after glucose loading in normoinsulinemic but not in hyperinsulinemic obese subjects. These results show that higher homocysteine levels are observed in the hyperinsulinemic obese subjects and suggest that homocysteine could play a role in the higher risk of cardiovascular disease in obesity.     

Glucose tolerance, plasma and pancreatic insulin levels in zinc deficient rats.

Two experiments were conducted to examine the effect of zinc deficiency on glucose tolerance, and on blood and pancreatic insulin concentrations. In the first study, no significant differences in blood glucose or plasma insulin levels were noted between pair-weighted zinc deficient and zinc sufficient rats after an oral glucose load. In the second experiment, the concentration of pancreatic insulin in pair-fed zinc sufficient rats did not differ significantly from that of zinc deficient rats. However, a zinc deficient group fed ad libitum had significantly lower pancreatic insulin levels, suggesting that food restriction may cause increased pancreatic insulin. Thus, zinc deficiency per se had no apparent effect on oral glucose tolerance or pancreatic insulin concentrations.     

Glucagon stimulation of hepatic gluconeogenesis in neonatal pigs.

The effect of an infusion of glucagon on gluconeogenesis was studied in 5-day-old piglets. Glucagon stimulated hepatic new glucose formation from lactate, but did not significantly change blood glucose or plasma free fatty acid levels. The data suggest that glucagon enhances substrate flow in the gluconeogenic pathway in neonatal animals.     

Improved cold tolerance in glucagon-treated rats

In glucagon-treated rats (50 μg/100g, twice a day, 4 wks, sc) (GTR), the weights of liver and interscapular brown adipose tissue (BAT), and the level of plasma glucagon increased as compared with those in the vehicle-treated controls (VC). Mitochondria of BAT were markedly developed in size and cristae. Cold tolerance as assessed by the rate of fall in colonic temperature at ?5 °C was improved. Elevations of colonic temperatures by noradrenaline (40 μg/100g, im) were significantly enhanced in GTR. After cold exposure, blood free fatty acids (FFA) and plasma glucagon levels increased, but blood glucose and β-hydroxybutyrate levels were not changed in VC. Both blood FFA and β-hydroxybutyrate levels increased and blood glucose level decreased, but plasma glucagon levels was not affected by cold exposure in GTR. These results suggest that glucagon is involved in cold acclimation by means of enhanced nonshivering thermogenesis, possibly due to an activation of BAT as well as increased production and utilization of ketone bodies in the liver.     

Plasma glucose and insulin responses to oral and intravenous glucose in cold-exposed humans

Although glucose tolerance and skeletal muscle glucose uptake are markedly improved by cold exposure in animals, little is known about such responses in humans. This study used two variations of a glucose tolerance test (GTT) to investigate changes in carbohydrate metabolism in healthy males during nude exposure to cold. In experiment 1, an oral GTT was performed in the cold and in the warm (3 h at 10 or 29 degrees C). To bypass the gastrointestinal tract, and to suppress hepatic glucose output, a second experiment was carried out as described above, using an intravenous GTT. Even though cold exposure raised metabolic rate greater than 2.5 times, plasma glucose and insulin responses to an oral GTT remained unaltered. In contrast, cold exposure reduced the entire plasma glucose profile as a function of time during the intravenous GTT (P less than 0.05), as plasma glucose was returned to basal levels within 1 h in comparison to a full 2 h in the warm, despite low insulin levels. The results of the intravenous GTT demonstrate that even with low insulin levels, carbohydrate metabolism is increased in cold-exposed males. This effect could be masked in the oral GTT by gastrointestinal factors and a high hepatic glucose output. Cold exposure may enhance insulin sensitivity and/or responsiveness for glucose uptake, mainly in shivering skeletal muscles.     

Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes.     

Role of fatty acid composition in the development of metabolic disorders in sucrose-induced obese rats

Fatty acids have been shown to be involved in the development of insulin resistance associated with obesity. We used sucrose loading in rats to analyze changes in fatty acid composition in the progression of obesity and the related metabolic disorder. Although rats fed a sucrose diet for 4 weeks had body weights similar to those of control animals, their visceral fat pads were significantly larger, and serum triglyceride levels were higher; however, neither plasma glucose nor insulin levels were significantly higher. After 20 weeks of sucrose loading, body weight and visceral and subcutaneous fat pads had increased significantly compared with those in control rats. Moreover, plasma glucose, insulin, and triglyceride levels were significantly higher. An analysis of individual fatty acid components in the blood and peripheral tissues demonstrated phase- and tissue-dependent changes. After 20 weeks of sucrose loading, palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9), the major components of monounsaturated fatty acid, showed a ubiquitous increase in plasma and all tissues analyzed. In contrast, linoleic acid (18:2 n-6) and arachidonic acid (20:4 n-6), the major components of polyunsaturated fatty acid in the n-6 family, decreased in plasma and all tissues analyzed. After 4 weeks of sucrose loading, these changes in fatty acid composition were observed only in the liver and plasma and not in fat and muscle. This led us to conclude that elevation of plasma glucose and insulin develop at the late phase of sucrose-induced obesity, when changes in fatty acid composition appear in fat and muscle. Furthermore, changes in fatty acid composition in liver seen after 4 weeks of sucrose loading, when increases in neither plasma glucose nor insulin were detected, suggest that liver may be the initial site of fatty acid imbalance and that aberrations in hepatic fatty acid composition may lead to fatty acid imbalances in other tissues.     

Effective control of glycemic status and toxicity in Zucker diabetic fatty rats with an orally administered vanadate compound

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulin-dependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After approximately 16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from approximately 17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only approximately 50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-obesity and Antidiabetic Effects of Deep Sea Water on ob/ob Mice

Recently, deep sea water (DSW) has started to receive much attention for therapeutic intervention in some lifestyle diseases. In this study, the anti-obesity and antidiabetic effects of DSW in ob/ob mice were investigated. The animals were randomly divided into two groups with six animals: control group received tap water; the experimental group was treated with DSW of hardness 1000 for 84 days. The body weight gain after 84 days in DSW-fed group was decreased by 7% compared to the control group. The plasma glucose levels in the DSW-fed mice were substantially reduced by 35.4%, as compared to control mice. The results of oral glucose tolerance test revealed that DSW-fed groups significantly increased the glucose disposal after 84 days. DSW increased plasma protein levels of adiponectin and decreased plasma protein levels of resistin, RBP4, and fatty acid binding protein. Moreover, GLUT4 and AMP-activated protein kinase levels in skeletal muscle tissue were increased while peroxisome proliferator-activated receptor γ and adiponectin were decreased in adipose tissue of DSW-fed mice. These results suggest that the antidiabetic and anti-obesity activities of DSW were mediated by modulating the expression of diabetes- and obesity-specific molecules. Taken together, these results provide a possibility that continuous intake of DSW can ameliorate obesity and diabetes.     

Hydrazonopropionic acids, a new class of hypoglycemic substances. 4. Hypoglycemic effect of 2-(3-methyl-cinnamylhydrazono)-propionate in the rat and guinea pig

The hydrazone-compound 2-(3-methyl-cinnamylhydrazono)-propionate (MCHP) significantly lowered the blood glucose concentration in fasted guinea pigs and rats. A significant decrease of blood glucose levels was observed in fasted guinea pigs already after an intraperitoneal injection of 20.5 mumol/kg MCHP, while much higher doses (about 1000 mumol/kg) were necessary to produce a hypoglycemic effect in the fasted rat. After oral administration MCHP (82.0 mumol/kg) significantly decreased the blood glucose concentration in guinea pigs. Furthermore MCHP caused a dose-dependent increase of plasma free fatty acid concentrations in guinea pigs and rats. In addition, MCHP decreased the concentrations of blood ketone bodies, plasma cholesterol and intrahepatic acetyl-coenzyme A in the guinea pig. All of these findings appear to be due to a reduced fatty acid utilization in the presence of MCHP resulting presumably in an intramitochondrial deficiency of acetyl-CoA. At hypoglycemic effective doses the intramitochondrial and cytoplasmatic redox ratios as well as the hepatic ATP/ADP ratio were not influenced by MCHP in fasted guinea pigs. Even at large doses (123 mumol/kg) MCHP decreased the activity of monoamino oxidase in guinea pigs only by less than 15%. Furthermore MCHP showed under our experimental conditions no relevant influence on the activity of various liver enzymes in plasma, the plasma concentration of creatinine, the plasma triglyceride-glycerol level and on the intrahepatic triglyceride-glycerol concentration of fasted guinea pigs. It is concluded that MCHP meets basic requirements for a potential oral antidiabetic agent.     

Supplementation of a novel microbial biopolymer, PGB1, from new Enterobacter sp. BL-2 delays the deterioration of type 2 diabetic mice

Antidiabetic effects of a novel microbial biopolymer (PGB)1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.