The incretin hormone glucagon-like peptide-1 enhances glucose-dependent insulin secretion and is therefore a most attractive therapeutic approach for the treatment of Type 2 Diabetes Mellitus. The anti-diabetic drug, metformin, has previously been shown to increase circulating levels of GLP-1, although its mechanism of action is currently unknown. Neither metformin nor AICAR (activators of AMPK) directly stimulated GLP-1 secretion from the L-cell in vitro. However, oral treatment of rats with metformin enhanced plasma levels of active and total GLP-1, independent of GLP-1 degradation. Furthermore, pre-treatment with the general muscarinic antagonist, atropine, or the M3 antagonist, 4-DAMP, decreased metformin–induced GLP-1 secretion, while M1 and M2 antagonists did not. Chronic bilateral subdiaphragmatic vagotomy had no effect, while the GRP antagonist, RC-3095, reduced metformin-induced GLP-1secretion. Therefore, I conclude that metformin-induced GLP-1 secretion occurs in part through the parasympathetic nervous system, the M3 and GRP receptors, but is independent of the vagus nerve.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31353 |
| Date | 15 December 2011 |
| Creators | Mulherin, Andrew |
| Contributors | Brubaker, Patricia |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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