Effects Of Glp-1 On Glucose Homeostasis

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GLP-1, a peptide produced by the enteroendocrine cells of the gut, can normalize blood glucose in type 2 diabetes, when given parenterally. Its mode of action is by increasing cAMP in beta cells of the pancreas through a specific G-protein coupled receptor. Prior to 2002 no long-term studies with chronic GLP-1 infusions had been performed. In collaboration with Dr. Grady Meneilly, Vancouver General Hospital, and Dr. Dariush Elahi, Massachusetts General Hospital, we performed a 3-month study whereby we infused GLP-1 continuously subcutaneously via Mini Med pump. Data showed no tachyphylaxis to the treatment and it maintained a glycated hemoglobin of 7%. This data provides confirmation that compounds under development for type 2 diabetes, whose mechanism of action is via activation of the GLP-1 receptor, are worth developing We are now presently investigating the actions of a metabolic of GLP-1, the 9-36 amide fragment. In vivo, after eating, the fragment accumulates in the plasma; hence we are undertaking a study to ascertain if it per se has biological properties. We had found that 9-36 amide, in insulin-resistant subjects, increases glucose disposal in liver. We are currently working on the mechanism of action.