Intra-islet regulation of hormone secretion by glucagon-like peptide-1-(7-36) amide

Glucagon-like peptide (GLP)-1-(7-36) amide, a peptide product of the posttranslational processing of pancreatic and intestinal proglucagon, has been shown to regulate insulin secretion. Monoclonal antibodies to glucagon and GLP-1-(7-36) amide were generated to localize GLP-1-(7-36) amide in the pancreatic islets by immunocytochemistry and radioimmunoassay. GLP-1-(7-36) amide immunoreactivity was found in some, but not all, glucagon-containing alpha-cells. Displaceable receptor binding for GLP-1(7-36) amide was found on cells immunoreactive for insulin, somatostatin, glucagon, and GLP-1. Direct effects of GLP-1-(7-36) amide and nonamidated GLP-1-(7-37) on hormone secretion were investigated using isolated pancreatic islet preparations. GLP-1-(7-37) and -(7-36) amide significantly increased insulin and somatostatin release in the concentration range of 0.01-100 nM in 11.0 mM glucose. GLP-1-(7-37) and -(7-36) amide had no effect on glucagon secretion in the presence of 11.0 mM glucose. GLP-1-(7-36) amide was released from isolated islets in response to 2.25, 5.5, and 11.0 mM glucose. These results suggest that pancreatic GLP-1 may be important in the regulation of intra-islet hormone secretion.