Mechanisms Mediating Antidiabetic Effects of Serviceberry extracts, Curcumin, and Stilbenes

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia in which homeostasis of carbohydrate and lipid metabolism is improperly regulated by insulin. Hippocrates (460-377 B.C), said “Let food be thy medicine and medicine be thy food”. The goal of this study was to characterize potential antidiabetic mechanisms of serviceberry extracts, and two polyphenolic bioactive components, curcumin and stilbenes. Serviceberry [Amelanchier alnifolia (Nutt.) Nutt. ex. M. Roem (Rosaceae)] has been traditionally used by the American Indians of Montana, in the management of diabetes. In this study, serviceberry plant samples consisting of leaves, twigs, and leaves with berries were extracted and fractionated. We demonstrate that serviceberry extracts activate AMPK (AMP-activated protein kinase), increase glucose uptake, and suppress dexamethasone-induced gluconeogenic gene expression. Additionally, water fractions from serviceberry leaves and twigs demonstrated significant inhibition of mammalian alpha-glucosidase activity, similar to that of acarbose, in vitro and in a diet-induced obesity mouse model of insulin resistance and diabetes. These findings validate traditional knowledge of the antidiabetic effects of serviceberry and indicate that serviceberry extracts delay intestinal absorption of carbohydrate and suppress hepatic glucose production. Curcumin and stilbenes are polyphenolic bioactive components that have been demonstrated to possess significant antioxidant and anti-inflammatory effects. Several studies demonstrate that curcuminoids and stilbenes, including resveratrol, can contribute to improved health, insulin sensitivity, and lower blood glucose levels in animal models of diabetes. In this study we demonstrated that curcuminoids increased the transcriptional activation of the nuclear receptor PPARγ. Consistent with PPARγ activation, curcumin-treatment increased gene expression and secretion of adiponectin. Interestingly, curcumin treatment did not induce differentiation of human subcutaneous preadipocytes and inhibited rosiglitazone-induced adipocyte differentiation in human subcutaneous preadipocytes. Natural stilbenes and synthetic analogs were investigated for alpha-glucosidase inhibitory effects in vitro and in vivo. Our studies demonstrate that resveratrol, a polyphenolic stilbene, and its naturally occurring analog, piceatannol, are potent inhibitors of mammalian alpha-glucosidase activity. These findings extend the range of the multifaceted beneficial properties of stilbene compounds, in blood glucose control and management of type 2 diabetes.