Overexpression of glucagon-like peptide-1 receptor in an insulin-secreting cell line enhances glucose responsiveness

Montrose‐Rafizadeh, Chahrzad; Wang, Y; Janczewski, Andrzej M.; Henderson, Terrance E.; Egan, Josephine M.

doi:10.1016/s0303-7207(97)00079-8

Cited by 33 publications

(24 citation statements)

References 33 publications

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“…To demonstrate the presence of functional GLP-1 receptors, cyclic AMP was measured according to the method of Montrose-Rafizadeh et al (1997a). Triplicate hippocampal neuronal cell cultures were treated with 10 nM GLP-1 and harvested at 5-min intervals after the onset of drug treatment for a total period of 30 min.…”

Section: Methodsmentioning

confidence: 99%

Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4

Perry¹,

Haughey²,

Mattson³

et al. 2002

J Pharmacol Exp Ther

332

254

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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.Although GLP-1 is produced by cells in the intestines and was discovered because of its effects on glucose metabolism (Doyle and Egan, 2001), recent studies have shown that GLP-1 can decrease feeding by acting on specific receptors in the brain. When injected intracerebroventricularly, GLP-1 dramatically reduces food and water intake (Gunn et al

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Section: Methodsmentioning

confidence: 99%

Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4

Perry¹,

Haughey²,

Mattson³

et al. 2002

J Pharmacol Exp Ther

332

254

View full text Add to dashboard Cite

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“…Other batches were washed three times in the buffer at 37°C to remove peptide, and left another 15 min before being washed three times in ice-cold phosphate buffer saline followed by lysis with the perchloric acid. The lysates (950 ml) were then transferred to microcentrifuge tubes and cAMP was measured, as described previously [15] using a cAMP [ 3 H] assay kit (Amersham, Arlington Heights, Ill., USA). Cellular protein was assayed using the Bradford method ( Bio-Rad, Richmond, Calif., USA) with bovine y-globulin as a standard.…”

Section: Methodsmentioning

confidence: 99%

Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations

et al. 1999

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“…Isolated β cells are known to produce much lower levels of cAMP than whole islets (Schuit and Pipeleers, 1985) and increased glucose concentrations have been extensively demonstrated to increase cAMP accumulation in whole islets (Grill and Cerasi, 1973;Sharp, 1979). cAMP is the main mediator of GLP-1 agonist action on acute molecular events in insulin secretion in β cells and overexpression of the GLP-1R in a clonal β cell line leads to increased resting levels of cAMP (Montrose-Rafizadeh et al, 1997a). Although cAMP is a widely adopted second messenger system for many receptors, specificity of response to external stimuli and effect on cell signaling pathways is conferred by regulation of its formation, degradation and spatial regulation by anchoring proteins (Cooper, 2003).…”

Section: Stimulation Of Camp Productionmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

584

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Overexpression of glucagon-like peptide-1 receptor in an insulin-secreting cell line enhances glucose responsiveness

Cited by 33 publications

References 33 publications

Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4

Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4

Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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