Effects of graded ?-glucosidase inhibition on sugar absorptionin vivo

Abstract

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.

Green and Chamomile Teas, but not Acarbose, Attenuate Glucose and Fructose Transport via Inhibition of GLUT2 and GLUT5

“…In rats, acarbose did not modify expression of SGLT1 nor GLUT2, the major glucose transporters in the small intestine, but modulated GLUT1 expression. However, these changes did not modify overall glucose transport, and furthermore, acarbose did not inhibit monosaccharide transport in rats . We show here that acarbose does not directly interact with human glucose and fructose transporters, GLUT2 and GLUT5, and does not inhibit glucose or fructose transport in differentiated Caco‐2 cell monolayers.…”

“…Acarbose would therefore be ineffective against fructose and glucose absorption from, for example, high fructose corn syrups, which contain ∼50% glucose and ∼50% fructose. On the other hand, acarbose would be effective in attenuating sucrose digestion as it inhibits sucrase activity as expected and indirectly slows the rate of transport of the products across the brush border through diminished substrate concentration. Chamomile and green teas, owing to their ability to inhibit both glucose and fructose transport, could be particularly beneficial for reducing liver inundation by fructose at the gastrointestinal level in addition to blunting blood glucose spikes.…”

Synthesis and characterization of the Zn(II) and Cu(II) piperidinyl isoeuxanthone complexes: DNA-binding and cytotoxic activity

“…1(a). The structural similarity and biological efficacy of xanthones encouraged many scientists to isolate or synthesize appropriately modified derivatives for the development of prospective new drug candidates [10][11][12][13].…”

Pharmacology of Glucosidase Inhibitors

“…Intraduodenal infusion of sucrose with graded doses of acarbose (0, 0.7-5.6mg/kg body weight) over a 150-min period in rats resulted in a significant, dose-dependent inhibition of the glucose elevation in the portal venous blood (MADARIAGA et al 1988).…”