Endocrine Abstracts

Annona squamosa has been shown to have anti-diabetic properties, although the underlying mechanisms are not fully known. In the present study, ethanol extract A. squamosa (EEAS) leaf were investigated in vitro and in vivo, to elucidate the mechanism underlying anti-diabetic actions. EEAS significantly (P<0.05–0•001) increased insulin release 2.2-5.5-folds at 5.6 mM/16.7 mM glucose at concentrations between 8-5000µg/ml from BRIN-BD11 cells. Similar insulin secretory responses to 25-200µg/ml EEAS were seen using isolated mouse islets with stimulatory effects comparable to 1µM GLP-1. Insulinotropic effects of EEAS (200µg/ml) on BRIN-BD11 cells were significantly inhibited by verapamil (30%), diazoxide (38%) and calcium free conditions (62%) showing importance of ion channels and Ca2+ in mechanism of action. Insulin secretion was further potentiated by activation of multiple pathways using IBMX (200µM, 1.5-fold, P<0.001), tolbutamide (200µM, 1.5-fold, P<0.05) and KCl (30 mM, 1.4-fold, P<0.001). At 200µg/ml, EEAS induced membrane depolarization and increased intracellular Ca2+ by 7 and 7.5-folds, respectively. EEAS significantly inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion in vitro. In addition, EEAS increased transport of glucose and insulin action in 3T3-L1 adipocytes. Following the ingestion of sucrose, EEAS substantially reduced postprandial hyperglycaemia and increased unabsorbed sucrose content throughout the GIT. EEAS reduced glucose absorption during in situ gut perfusion with glucose. EEAS inhibited intestinal disaccharidase enzyme activity and increased gastrointestinal motility. Thus, EEAS improves glycaemic control through a variety of mechanisms. Further studies are needed to identify the molecular compounds of EEAS that play a vital role in the treatment of type 2 diabetes mellitus.