Inhibition of glucose absorption in the rat jejunum: a novel action of alpha-D-glucosidase inhibitors.
OBJECTIVE
alpha-D-Glucosidase inhibitors act primarily by decreasing disaccharide hydrolysis and thus reduce the amount of free monosaccharides available for absorption. A novel action of alpha-D-glucosidase inhibitors is presented, indicating a direct effect on free glucose absorption by the rat jejunum.


METHODS
The jejunum was isolated and free hexose was measured using in vivo single-pass luminal perfusion and dual vascular and luminal single-pass in vitro perfusion. Xenopus oocytes were injected with RNA transcript encoding recombinant sodium-glucose cotransporter 1, and uptake of 3H-labeled 3-O-methyl-D-glucopyranose (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 appearance of 3-O-MG in the vascular effluent by 28% and 60%, respectively. Accumulation of D-glucose within the enterocytes was decreased significantly 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 cotransporter 1.


CONCLUSIONS
The findings indicate that alpha-D-glucosidase inhibitors act specifically on the entry of free glucose into the enterocyte, an additional means by which they can reduce postprandial hyperglycemia.
Hirsh
A J
AJ
Department of Physiology, University of Alberta, Edmonton, Canada.
Yao
S Y
SY
Young
J D
JD
Cheeseman
C I
CI
D020909:Acarbose; D000818:Animals; D003511:Cyclohexanols / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006601:Hexoses / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1; D014312:Trisaccharides / Q000494:pharmacology
D003511:Cyclohexanols; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006601:Hexoses; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D051269:Sodium-Glucose Transporter 1; D014312:Trisaccharides; C054577:AO 128; D010695:Phlorhizin; D005947:Glucose; D020909:Acarbose