Effects Of Glp-1 On Glucose Homeostasis

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GLP-1 [7-36] amide is a naturally produced insulinotropic peptide which modulates insulin secretion from beta cells in the post-prandial state. Pharmacological doses are required to normalize blood glucose in type 2 diabetes. It is produced as a 30-amino acid peptide but within a few minutes the first two amino acids of the N-terminus (HA) are removed by a dipeptidyl peptidase IV, rendering the remaining GLP-1 [9-36] amide inactive as an insulinotropic peptide. In the post-prandial state, at least 75% of the GLP-1 is in the [9-36] form. Our previous investigators had found that GLP-1 [7-36] amide infusions not only increased insulin secretion but increased glucose disposal in liver, independent of insulin. In order to separate effects of GLP-1 [7-36] amide from its metabolite [9-36] and in conjunction with Grady Meneilly, M.D. (Vancouver General Hospital] and Dariush Elahi, Ph.D. (University of Worcester, MA) we have been infusing GLP-1 [9-36] amide to lean and obese subjects in order to elucidate if it had only intrinsic metabolic effects. We have found that GLP-1 [9-36] amide infusions result in increased glucose uptake by liver in obese, but not lean, subjects. This mirrors what we found with GLP-1 [7-36] amide infusion. The mechanism of action underlying the increased glucose uptake remains unresolved.