Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice

The importance of pancreatic versus intestinal-derived GLP-1 for glucose homeostasis is controversial. We detected active GLP-1 in the mouse and human pancreas, albeit at extremely low levels relative to glucagon. Accordingly, to elucidate the metabolic importance of intestinal proglucagon-derived peptides (PGDPs), we generated mice with reduction of Gcg expression within the distal (GcgDistalGut−/−) or entire (GcgGut−/−) gut. Substantial...