A schematic model displaying the opposite alterations of GLP-1/GLP-1R system in enteropancreatic axis in T1DM and T2DM experimental diabetes. (a) In STZ-induced T1DM, GLP-1 secretion from intestinal L cells and pancreatic alpha cells is increased (upward thin arrows). However, STZ toxicity causes severe loss of pancreatic beta cells and mild loss of extrapancreatic gastric glands parietal cells with the resulting decrease of the GLP-1 receptor (downward thin arrows). The discrepancy between increased GLP-1 secretion and reduced GLP-1R expression results in severely impaired GLP-1/GLP-1R signaling in pancreas and to a lesser degree in the stomach (broken thin and thick arrows). (b) HE diet-induced T2DM is characterized by increased GLP-1R on beta cells in pancreas and gastric parietal cells which are also increased in number as well as increased GLP-1 secretion from pancreatic alpha cells and extrapancreatic intestinal L cells (upward thin arrows). The joint increase in GLP-1 secretion and GLP-1R expression in enteropancreatic axis results in upregulation of endocrine and paracrine GLP-1/GLP-1R signaling in pancreas and stomach (thick arrows). P: pancreas; S: stomach; I: ileum.