Effects of graded alpha-glucosidase inhibition on sugar absorption in vivo.
The effect of inhibition of disaccharidases on the degree of absorption of glucose, lactose, and sucrose was examined utilizing an in vivo model in the rat. Acarbose, a competitive alpha-glucosidase inhibitor was utilized to selectively inhibit small intestinal mucosal enzymes. Adult rats (250-350 g body weight) were the subjects of intraduodenal bolus infusion experiments with either sugar alone or sugar plus acarbose. All sugars were infused at a dose of 0.5 g/kg body weight. Portal venous blood glucose was determined at 30-min intervals from 0 to 150 min. Glucose (monosaccharide) and lactose (beta-galactoside) absorption were not altered by the presence of acarbose. In contrast, sucrose (alpha-glucosidase) absorption was significantly diminished in the presence of acarbose. Sucrose absorption in the presence of increasing acarbose doses (0.7-5.6 mg/kg body weight) was depressed in a dose-dependent fashion. Linear regression analysis revealed a high degree of correlation between residual sucrase activity and area under blood glucose curve (r = 0.9837). Similar degrees of correlation were found between acarbose dose and area under blood glucose curve (r = -0.9322), and between residual sucrase activity and acarbose dose (r = -0.9695). These data confirm that acarbose is a selective alpha-glucosidase inhibitor that does not affect monosaccharidase transport. In the presence of acarbose, alpha-glucosidase absorption is diminished in a dose-dependent fashion. Postprandial glucose rise following an alpha-glucosidase meal seems to be determined, in the presence of graded acarbose inhibition, by residual mucosal alpha-glucosidase activity.
Madariaga
H
H
International Institute for Infant Nutrition and Gastrointestinal Disease, Children's Hospital of Buffalo.
Lee
P C
PC
Heitlinger
L A
LA
Lebenthal
E
E
D020909:Acarbose; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006868:Hydrolysis; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D007785:Lactose / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013395:Sucrose / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014312:Trisaccharides / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D014312:Trisaccharides; D013395:Sucrose; D005947:Glucose; D007785:Lactose; D020909:Acarbose