alpha-Glucosidase inhibitors prevent diet-induced increases in intestinal sugar transport in diabetic mice.
The recommended diet for diabetes mellitus is rich in complex carbohydrates. We have previously shown that high carbohydrate levels in the intestinal lumen induce adaptive increases in sugar absorption which in turn exacerbate postprandial hyperglycemia in diabetic mice. alpha-Glucosidase inhibitors (AGIs) hinder digestion of complex carbohydrates and therefore alleviate postprandial glycemic excursions. In this study, we tested the hypothesis that AGIs prevent the carbohydrate-induced upregulation of intestinal glucose and fructose transport in diabetes. Streptozotocin-diabetic mice were fed the following isocaloric diets: high carbohydrate (H), H plus acarbose (HA), H plus deoxy-nojirimycin (HD), and low carbohydrate (L), then nutrient uptakes were determined after 2 and 4 weeks. Body weight, intestinal weight, and length were independent of diet. Fasting and postprandial blood glucose levels were lower in HA and HD than in H mice. Uptakes of D-glucose and D-fructose were 2 to 3 times greater in H than in L mice, but HA and HM diets gradually reduced D-glucose uptakes to rates similar to L mice. Only HA diets reduced D-fructose uptake. Intestinal proline, aspartate, and glutamine uptakes were each greater in L than in H, HA, and HD mice. alpha-Glucosidase inhibitors did not alter intestinal permeability and amino acid transport rates. alpha-Glucosidase inhibitor-inhibitable increases in total intestinal absorptive capacity for sugars were due to carbohydrate-induced increases in V(max) of glucose transport. Clearly, one potential mechanism by which AGIs blunt postprandial glycemic excursions and lower fasting blood glucose concentrations in individuals consuming carbohydrate-containing diets is by preventing carbohydrate-induced increases in intestinal sugar transport.
Casirola
Donatella M
DM
Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101-1709, USA.
Ferraris
Ronaldo P
RP
D000818:Animals; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental; D004032:Diet; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007408:Intestinal Absorption; D008297:Male; D051379:Mice
D004040:Dietary Carbohydrates; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents