Acute Reduction of Incretin Effect and Glucose Intolerance in Rats by Single Intragastric Administration of 3-deoxyglucosone.

Secretion of glucagon-like peptide-1 has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. 3-Deoxyglucosone, a dietary composition, has been suggested as an independent factor for the development of prediabetes. A-pathophysiological very high condition of 3DG concentrations administered i. v. induced acute glucose intolerance in rats. In this study, to examine the acute effects of single intragastric administration of 3DG at dose of potentially single-meal intake on plasma glucose, insulin, glucagon, total GLP-1 and total GIP levels in response to a glucose load, OGTT was performed immediately in normal Kunming mice or Sprague-Dawleys rats after 3DG administration. GLP-1 secretion, intracellular cAMP levels and 2-NBDG uptake were examined in STC-1 cells exposured to 3DG. In rats, 20 mg/kg 3DG i.g. (3DG-20 i.g.) impaired glucose tolerance (P<0.05) with increased AUC (1 070±105.2 vs. 918.0±91.20, P<0.05). The mice treated with 3DG-20 i.g. exhibited a similar effect, independent of the effect of plasma 3DG concentration. 3DG-20 i.g. treatment reduced plasma insulin concentrations with decreased AUC (3 552±300.2 vs. 4 715±420.5, P<0.05) in rats whereas plasma glucagon levels were not significantly different. These changes occurred in conjunction with decreased plasma GLP-1 and GIP levels (P<0.05). Furthermore, non-cytotoxic 3DG concentrations directly reduced GLP-1 secretion in STC-1, at least in part, by decreasing intracellular cAMP level and glucose uptake. We demonstrated for the first time that single intragastric administration of 3DG resulted in acute reduction of incretin effect and glucose intolerance, which was associated with a decrease in the biological function of GLP-1 by decreasing GLP-1 secretion. © Georg Thieme Verlag KG Stuttgart · New York.