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Old 09-13-2007, 05:26 PM
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olsen olsen is offline
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olsen olsen is offline
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Join Date: Aug 2006
Posts: 1,860
15 yr Member
Default effects of byetta

from an earlier post--seems the neuro effects are in addition to the anti-diabetic effects. the mechanisms of action differ for the 2 different systems (ie pancreas, sml bowel, colon for diabetes and neurons within the nervous system for neurological effects)

J Pharmacol Exp Ther. 2002 Mar;300(3):958-66.
A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells.Perry T, Lahiri DK, Chen D, Zhou J, Shaw KT, Egan JM, Greig NH.

Section of Drug, Design, and Development, Laboratory of Neuroscience, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. perryt@grc.nia.nih.gov

The insulinotropic hormone glucagon-like peptide-1 (7-36)-amide (GLP-1) has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation and is presently in clinical trials as a therapy for type 2 diabetes mellitus. We report on the effects of GLP-1 and two of its long-acting analogs, exendin-4 and exendin-4 WOT, on neuronal proliferation and differentiation, and on the metabolism of two neuronal proteins in the rat pheochromocytoma (PC12) cell line, which has been shown to express the GLP-1 receptor. We observed that GLP-1 and exendin-4 induced neurite outgrowth in a manner similar to nerve growth factor (NGF), which was reversed by coincubation with the selective GLP-1 receptor antagonist exendin (9-39). Furthermore, exendin-4 could promote NGF-initiated differentiation and may rescue degenerating cells after NGF-mediated withdrawal. These effects were induced in the absence of cellular dysfunction and toxicity as quantitatively measured by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays, respectively. Our findings suggest that such peptides may be used in reversing or halting the neurodegenerative process observed in neurodegenerative diseases, such as the peripheral neuropathy associated with type 2 diabetes mellitus and Alzheimer's and Parkinson's diseases. Due to its novel twin action, GLP-1 and exendin-4 have therapeutic potential for the treatment of diabetic peripheral neuropathy and these central nervous system disorders.

PMID: 11861804 [PubMed - indexed for MEDLINE]
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