Enteric glucagon 37 rather than pancreatic glucagon 29 stimulates glucose absorption in rat intestine

Abstract

Background & Aims: Glucose and galactose are absorbed by the small intestine via the sodium-dependent glucose transporter 1 (SGLT1) and fructose via the facilitated glucose transporter 5. A stimulatory effect of enteric glucagon 37 and pancreatic glucagon 29 on intestinal carbohydrate absorption has been shown. However, only glucagon 37 is released after nutrient uptake and would thus fit into a regulatory circuit of nutrient-dependent hormone release that enhances carbohydrate absorption. Therefore, the aim of the present study was to evaluate whether glucagon 37 rather than glucagon 29 is the physiological stimulus of intestinal glucose absorption. Methods: We examined the effects of glucagon 37, glucagon 29, and dibutyryl adenosine 3',5'-cyclic monophosphate on intestinal carbohydrate absorption and hepatic glucose output in the isolated perfused small intestine, isolated enterocytes, and isolated perfused liver of the rat. Results: Reciprocal dose-response curves for the effects of the two hormones in intestine and liver were demonstrated: glucagon 37 was one order of magnitude more potent than glucagon 29 in increasing intestinal absorption of glucose via the SGLT1. In contrast, glucagon 29 more efficiently stimulated hepatic glucose release. The intracellular messenger was shown to be adenosine 3',5'-cyclic monophosphate. Conclusions: Glucagon 37 rather than glucagon 29 is the physiological stimulus of intestinal glucose absorption and exerts its effect via a specific glucagon 37 receptor. GASTROENTEROLOGY 1998;115:1163-1171