Huang-Lian-Jie-Du-Tang supplemented with Schisandra chinensis Baill. and Polygonatum odoratum Druce improved glucose tolerance by potentiating insulinotropic actions in islets in 90% pancreatectomized diabetic rats.

We investigated to determine what effects, if any, the respective water extracts of Radix scutellariae (RS), Fructus schisandrae chinensis (FSC), Huang-Lian-Jie-Du-Tang (HLJDT), and HLJDT supplemented with FSC, and Rhizoma Polygonati odorati (HLJDT-M) would have on glucose tolerance by modulating glucose-stimulated insulin secretion, beta-cell mass, and morphometry in 90% pancreatectomized (Px) diabetic rats fed high-fat diets. Through the elevation of intracellular cAMP levels, FSC RS, HLJDT, and HLJDT-M increased insulin secretion in Min6 cells and GLP-1 secretion in NCI-H716 cells. After an 8-week period of treatment, it was found that HLJDT-M improved glucose tolerance in an oral glucose tolerance test in Px rats. HLJDT-M also potentiated first- and second-phase insulin secretion, but RS and HLJDT elevated only the second phase at hyperglycemic clamp. RS and HLJDT increased beta-cell mass by hyperplasia and hypertrophy, while HLJDT-M increased it only by hyperplasia. The rise in hyperplasia was associated with elevated IRS2 and PDX-1 expression in the islets. In conclusion, HLJDT-M worked as an anti-diabetic prescription by enhancing insulinotropic actions in diabetic rats.

Kochujang, a Korean fermented red pepper plus soybean paste, improves glucose homeostasis in 90% pancreatectomized diabetic rats.

OBJECTIVES: Red pepper and soybeans have been reported to modulate energy and glucose metabolism. However, the antidiabetic effect of kochujang, the fermented product of red pepper plus soybeans, has not been studied. We examined whether kochujang affected insulin secretion from beta-cells and/or peripheral insulin resistance in 90% pancreatectomized diabetic rats fed high-fat diets. METHODS: Diabetic rats consumed a high-fat diet containing two different kinds of 5% kochujang powder or the equivalent amount of nutrients for 8 wk. Two types of kochujang were made through the fermentation of two different kinds of meju (soybeans), red peppers, glutinous rice, and malts. Meju was produced by fermenting soybeans in a traditional method (TMK) or in a more modern method in which soybeans are inoculated with Bacillus subtilus and Aspergillus sojae (MMK). RESULTS: TMK and MMK decreased body weight, visceral fat, and serum leptin levels without modulating caloric intake in diabetic rats compared with the control. TMK and MMK also improved glucose tolerance by enhancing insulin sensitivity but did not potentiate glucose-stimulated insulin secretion. The improvement in hepatic insulin sensitivity caused by TMK and MMK was explained by the potentiated phosphorylation of signal transducer and activator of transcription-3 --> adenosine monophosphate kinase --> acetyl-coenzyme A carboxylase and decreased phosphoenolpyruvate carboxykinase expression. Kochujang diets reduced hepatic glucose output and triacylglycerol accumulation and increased glycogen storage. CONCLUSION: The combination of red pepper and fermented soybeans in kochujang improves glucose homeostasis by reducing insulin resistance, not by enhancing beta-cell function, in diabetic rats. The improvement is associated with decreased hepatic fat storage by the activation of adenosine monophosphate kinase.

Long-term consumption of saponins derived from Platycodi radix (22 years old) enhances hepatic insulin sensitivity and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed a high-fat diet.

Crude saponins derived from Chinese Platycodi radix have been reported to prevent increases in body weight and liver TAG in mice fed a high-fat diet. We investigated the effects of an extract (PR) taken from Korean Platycodi radix, which is cultivated for 22 years in the ground (Jangsaeng doraji), and its saponins (PRS) on insulin resistance and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed high-fat diets. Four groups were orally supplemented with 2 g PR, 0.2 g PRS, 20 mg rosiglitazone (positive control) or 0.5 g cellulose (negative control) per kg body weight on a daily basis for 8 weeks. We found that PRS lowered body weight, visceral fat mass and serum leptin levels in pancreatectomized rats in comparison to the control. PR enhanced first- and second-phase insulin secretion while PRS stimulated only first-phase insulin secretion. Glucose infusion rates to maintain euglycaemia at hyperinsulinaemic states decreased in a descending order of rosiglitazone, PRS, PR and control, but they increased hepatic glucose output in the same order. This reduction was associated with the storage of decreased TAG and increased glycogen, which was a result of enhanced tyrosine phosphorylation of anti-insulin receptor substrate-2 and serine473 phosphporylation of protein kinase B (PKB, Akt). Improved hepatic insulin signalling led to decreased phosphoenolpyruvate carboxykinase expression and reduced hepatic glucose output accordingly. In conclusion, PRS principally improves glucose homeostasis by enhancing hepatic insulin sensitivity as a consequence of reducing fat storage and stimulating insulin signalling in diabetic rats. In addition, PR contains components that promote glucose-stimulated insulin secretion.

Long-term effects of central leptin and resistin on body weight, insulin resistance, and beta-cell function and mass by the modulation of hypothalamic leptin and insulin signaling.

To determine the long-term effect of central leptin and resistin on energy homeostasis, peripheral insulin resistance, and beta-cell function and mass, intracerebroventricular (ICV) infusion of leptin (3 ng/h), resistin (80 ng/h), leptin plus resistin, and cerebrospinal fluid (control) was conducted by means of an osmotic pump for 4 wk on normal rats and 90% pancreatectomized diabetic rats fed 40% fat-energy diets. Overall, the effects were greater in diabetic rats than normal rats. Leptin infusion, causing a significant reduction in food intake, decreased body weight and epididymal fat. However, resistin and leptin plus resistin reduced epididymal fat with decreased serum leptin levels in comparison with the control. Unlike serum leptin, only resistin infusion lowered serum resistin levels. Central leptin increased glucose infusion rates during euglycemic hyperinsulinemic clamp and suppressed hepatic glucose production in the hyperinsulinemic state in comparison with the control. However, central leptin did not affect glucose-stimulated insulin secretion and beta-cell mass. Central resistin infusion also increased peripheral insulin sensitivity, but not as much as leptin. Unlike leptin, resistin significantly increased first-phase insulin secretion during hyperglycemic clamp and beta-cell mass by augmenting beta-cell proliferation. These metabolic changes were associated with hypothalamic leptin and insulin signaling. ICV infusion of leptin potentiated signal transducer and activator of transcription 3 phosphorylation and attenuated AMP kinase in the hypothalamus, but resistin had less potent effects than leptin. Leptin enhanced insulin signaling by potentiating IRS2-->Akt pathways, whereas resistin activated Akt without augmenting insulin receptor substrate 2 phosphorylation. In conclusion, long-term ICV infusion of leptin and resistin independently improved energy and glucose homeostasis by modulating in different ways hypothalamic leptin and insulin signaling.

Exercise enhances insulin and leptin signaling in the cerebral cortex and hypothalamus during dexamethasone-induced stress in diabetic rats.

Exercise and dexamethasone (DEX) are known to have opposite effects on peripheral insulin resistance. However, their effects and mechanism on brain glucose metabolism have been poorly defined. We investigated the modulation of the hypothalamo-pituitary-adrenal (HPA) axis and insulin/leptin signaling associated with glucose utilization in the brains of 90% pancreatectomized diabetic rats, which had been administered two dosages of DEX and exercised for 8 weeks. The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression. In parallel with the modulated signaling, glucose utilization, such as glycogen storage and glycogen synthase activity, was suppressed by DEX in the cortex and hypothalamus, while exercise offset the DEX effects. Despite a decrease in epididymal fat mass, HDEX increased serum leptin levels, possibly due to an activated HPA axis, while exercise suppressed the increment. However, DEX reduced leptin-induced STAT3 phosphorylation in the cortex and hypothalamus, and it increased AMP-activated protein kinase (AMPK) phosphorylation only in the hypothalamus. Exercise reversed the phosphorylation of STAT3 and AMPK which had been modulated by DEX. In conclusion, exercise improves insulin and leptin signaling in the cerebral cortex and hypothalamus of diabetic rats exacerbated with HDEX, contributing to the regulation of body weight and glucose homeostasis.