The prevalence and progression of type 2 diabetes have increased remarkably in postmenopausal women. Although estrogen replacement and exercise have been studied for their effect in modulating insulin sensitivity in the case of insufficient estrogen states, their effects on beta-cell function and mass have not been studied. Ovariectomized (OVX) female rats with 90% pancreatectomy were given a 30% fat diet for 8 wk with a corresponding administration of 17beta-estradiol (30 microg/kg body weight) and/or regular exercise. Amelioration of insulin resistance by estrogen replacement or exercise was closely related to body weight reduction. Insulin secretion in first and second phases was lower in OVX during hyperglycemic clamp, which was improved by estrogen replacement and exercise but not by weight reduction induced by restricted diets. Both estrogen replacement and exercise overcame reduced pancreatic beta-cell mass in OVX rats via increased proliferation and decreased apoptosis of beta-cells, but they did not exhibit an additive effect. However, restricted diets did not stimulate beta-cell proliferation. Increased beta-cell proliferation was associated with the induction of insulin receptor substrate-2 and pancreatic homeodomain protein-1 via the activation of the cAMP response element binding protein. Estrogen replacement and exercise shared a common pathway, which led to the improvement of beta-cell function and mass, via cAMP response element binding protein activation, explaining the lack of an additive effect with combined treatments. In conclusion, decreased beta-cell mass leading to impaired insulin secretion triggers glucose dysregulation in estrogen insufficiency, regardless of body fat. Regular moderate exercise eliminates the risk factors of contracting diabetes in the postmenopausal state.

Type 2 diabetes is a heterogeneous metabolic disorder characterized by the impairment of insulin secretion from pancreatic b-cells and insulin resistance in peripheral tissues such as the liver, skeletal muscle and adipose tissue.1) In most cases, insulin resistance mostly precedes the impairment of insulin secretion in humans. For example, obesity induces hepatic, skeletal muscle and adipocyte insulin resistance, and hypersecretion of insulin maintains normoglycemia by compensating for insulin resistance. As long as insulin secretion compensates for peripheral insulin resistance, diabetes is not developed and exacerbated. Thus, herbs or drugs for type 2 diabetes mellitus should have an insulin sensitizing action to relieve insulin resistance and an insulinotropic action to improve glucose-stimulated insulin secretion and pancreatic b-cell survival.Extracts from Coptidis Rhizoma (CR) and Cortex Phellodendri, a Southeast Asian herb, have been used to treat diabetes mellitus for more than one thousand years in the history of Chinese medicinal remedies. , one of the main constituents of CR and Cortex Phellodendri, is a type of isoquinoline alkaloid, suggesting that it is a candidate of the principal anti-diabetic constituents of CR. According to reports, 2-4) berberine acts as an a-adrenoceptor antagonist. In addition, some aadrenoceptor antagonists, such as phentolamine, stimulate insulin release by inhibiting pancreatic b-cell ATP-sensitive potassium channels. 5,6) Berberine is a candidate for insulin secretagogues, but it's effect was not sufficient to recommend CR or berberine to treat type 2 diabetes. Post-prandial hyperglycemia is a prominent early defect in type 2 diabetes, predominantly due to loss of acute phase insulin secretion after eating. 7,8) Thus, insulin secretagogues have long been used as a diabetic drug to reduce post-prandial hyperglycemia to normal levels. Insulin secretagogues such as sulfonylurea make normoglycemia in the early stage of diabetes. However, most of them stimulate insulin secretion with and without glucose challenge by closing ATP-sensitive potassium channels in b-cells. 7,8) As a result, they increase insulin secretion without glucose loading, resulting in exhausting and damaging b-cells and frequent hypoglycemia. Eventually, they exacerbate the symptoms of diabetes. The ideal agent to treat post-prandial hyperglycemia should restore the acute-phase insulin secretion without hypoglycemia and enhance pancreatic b-cell survival. Thus, an insulinotropic agent is a better anti-diabetic agent than a simple insulin secretagogue. Insulinotropic agents, such as glucagon like peptide-1 receptor agonist (exendin-4), improve glucose-stimulated acute insulin secretion with the expansion of b-cell mass through improving insulin like growth factors (IGF)-1 and/or insulin. [9][10][11] In the present study, the fractions of CR were investigated for their effects as an insulin sensitizer through insulin-mediated glucose uptake in 3T3-L1 adipocytes and as an insulinotropic agent in Min6 cells. ...

Based on these results, the fermentation of soybeans predominantly with Bacillus subtilis generated isoflavonoid aglycones and small peptides, which improved insulinotropic action in islets of type 2 diabetic rats. Overall, the anti-diabetic action of CKJ was superior to CSB in type 2 diabetic rats.

Long-term dexamethasone (DEX) treatment is well known for its ability to increase insulin resistance in liver and adipose tissues leading to hyperinsulinemia. On the other hand, exercise enhances peripheral insulin sensitivity. However, it is not clear whether DEX and/or exercise affect b-cell mass and function in diabetic rats, and whether their effects can be associated with the modulation of the insulin/IGF-I signaling cascade in pancreatic b-cells. After an 8-week study, whole body glucose disposal rates in 90% pancreatectomized (Px) and sham-operated male rats decreased with a high dose treatment of DEX (0$1mg DEX/kg body weight/day)(HDEX) treatment, while disposal rates increased with exercise. First-phase insulin secretion was decreased and delayed by DEX via the impairment of the glucose-sensing mechanism in b-cells, while exercise reversed the impairment of first-phase insulin secretion caused by DEX, suggesting ameliorated b-cell functions. However, exercise and DEX did not alter secondphase insulin secretion except for the fact that HDEX decreased insulin secretion at 120 min during hyperglycemic clamp in Px rats. Unlike b-cell functions, DEX and exercise exhibited increased pancreatic b-cell mass in two different pathways. Only exercise, through increased proliferation and decreased apoptosis, increased b-cell mass via hyperplasia, which resulted from an enhanced insulin/IGF-I signaling cascade by insulin receptor substrate 2 induction. By contrast, DEX expanded b-cell mass via hypertrophy and neogenesis from precursor cells, rather than increasing proliferation and decreasing apoptosis. In conclusion, the improvement of b-cell function and survival via the activation of an insulin/IGF-I signaling cascade due to exercise has a crucial role in preventing the development and progression of type 2 diabetes.