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Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2002 Sep; Vol. 302 (3), pp. 881-8. - Publication Year :
- 2002
-
Abstract
- Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the L cells of the gastrointestinal tract in response to food. It has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation. In type 2 diabetes, GLP-1, by continuous infusion, can normalize blood glucose and is presently being tested in clinical trials as a therapy for this disease. More recently, GLP-1 has been found to have central nervous system (CNS) effects and to stimulate neurite outgrowth in cultured cells. We now report that GLP-1, and its longer-acting analog exendin-4, can completely protect cultured rat hippocampal neurons against glutamate-induced apoptosis. Extrapolating these effects to a well defined rodent model of neurodegeneration, GLP-1 and exendin-4 greatly reduced ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity in basal forebrain cholinergic neurons. These findings identify a novel neuroprotective/neurotrophic function of GLP-1 and suggest that such peptides may have potential for halting or reversing neurodegenerative processes in CNS disorders, such as Alzheimer's disease, and in neuropathies associated with type 2 diabetes mellitus.
- Subjects :
- Animals
Basal Ganglia pathology
Cell Death drug effects
Cell Survival drug effects
Cells, Cultured
Choline O-Acetyltransferase metabolism
Cyclic AMP metabolism
Excitatory Amino Acid Agonists toxicity
Exenatide
Glial Fibrillary Acidic Protein metabolism
Glucagon metabolism
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Hippocampus cytology
Hippocampus drug effects
Ibotenic Acid antagonists & inhibitors
Ibotenic Acid toxicity
Immunohistochemistry
Neurons pathology
Parasympathetic Nervous System drug effects
Peptide Fragments metabolism
Protein Precursors metabolism
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Receptors, Glucagon drug effects
Receptors, Glucagon metabolism
Excitatory Amino Acid Antagonists toxicity
Glucagon pharmacology
Glutamic Acid toxicity
Nerve Degeneration chemically induced
Nerve Degeneration prevention & control
Neurons drug effects
Peptide Fragments pharmacology
Peptides pharmacology
Protein Precursors pharmacology
Venoms
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 302
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 12183643
- Full Text :
- https://doi.org/10.1124/jpet.102.037481