INHIBITION OF GLUCOSE-ABSORPTION IN THE RAT JEJUNUM - A NOVEL ACTION OF ALPHA-D-GLUCOSIDASE INHIBITORS

Background & Aims: alpha-D-Glucosidase inhibitors act primarily by dec reasing disaccharide hydrolysis and thus reduce the amount of free mon osaccharides available for absorption. A novel action of alpha-D-gluco sidase inhibitors is presented, indicating a direct effect on free glu cose absorption by the rat jejunum. Methods: The jejunum was isolated and free hexose was measured using in vivo single-pass luminal perfusi on and dual vascular and luminal single-pass in vitro perfusion. Xenop us oocytes were injected with RNA transcript encoding recombinant sodi um-glucose cotransporter 1, and uptake of H-3-labeled 3-O-methyl-D-glu copyranose (3-O-MG) was assessed. Results: Acarbose (0.1 mg/mL), added to the lumen, decreased D-glucose absorption by 20% in vivo. Addition of 0.1 or 1.0 mg/mL acarbose to the lumen in vitro decreased the appe arance of 3-O-MG in the vascular effluent by 28% and 60%, respectively . Accumulation of D-glucose within the enterocytes was decreased signi ficantly by 67% and 79% when acarbose (1 mg/mL) or phloridzin (2 mmol/ L), respectively, were present in the luminal perfusate. In contrast, acarbose did not affect the transport rate of free D-fructose and did not inhibit 3-O-MG uptake in oocytes expressing sodium-glucose cotrans porter 1. Conclusions: The findings indicate that alpha-D-glucosidase inhibitors act specifically on the entry of free glucose into the ente rocyte, an additional means by which they can reduce postprandial hype rglycemia.