A novel neurotrophic property of glucagon-like peptide 1

A promoter of nerve growth factor-mediated differentiation in PC12 cells

Tracyann Perry, Debomoy Lahiri, Demao Chen, J. I E Zhou, Karen T Y Shaw, Josephine M. Egan, Nigel H. Greig

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)958-966
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume300
Issue number3
DOIs
StatePublished - 2002

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Glucagon-Like Peptide 1
PC12 Cells
Nerve Growth Factor
Peripheral Nervous System Diseases
Islets of Langerhans
Type 2 Diabetes Mellitus
Insulin
Diabetic Neuropathies
Central Nervous System Diseases
Bromides
L-Lactate Dehydrogenase
Neurodegenerative Diseases
Parkinson Disease
Alzheimer Disease
exenatide
Clinical Trials
Hormones
Gene Expression
Glucose
Peptides

ASJC Scopus subject areas

  • Pharmacology

Cite this

A novel neurotrophic property of glucagon-like peptide 1 : A promoter of nerve growth factor-mediated differentiation in PC12 cells. / Perry, Tracyann; Lahiri, Debomoy; Chen, Demao; Zhou, J. I E; Shaw, Karen T Y; Egan, Josephine M.; Greig, Nigel H.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 300, No. 3, 2002, p. 958-966.

Research output: Contribution to journalArticle

Perry, Tracyann ; Lahiri, Debomoy ; Chen, Demao ; Zhou, J. I E ; Shaw, Karen T Y ; Egan, Josephine M. ; Greig, Nigel H. / A novel neurotrophic property of glucagon-like peptide 1 : A promoter of nerve growth factor-mediated differentiation in PC12 cells. In: Journal of Pharmacology and Experimental Therapeutics. 2002 ; Vol. 300, No. 3. pp. 958-966.
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