Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung

Kanse, Sandip M.; Kreymann, B.; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.1016/0014-5793(88)81063-9

Cited by 106 publications

(56 citation statements)

References 19 publications

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“…The GLP-1 receptor is present in the brain and pancreas (Campos et al, 1994;Bullock et al, 1996) and it couples positively to the adenylyl cyclase system (Drucker et al, 1987;Wheeler et al, 1993). Ligand activation of the G␣ s -linked GLP-1 receptor stimulates adenylyl cyclase, leading to increases in intracellular cAMP in pancreatic ␤-cells (Holz et al, 1999) and in rat hypothalamic membrane preparations (Kanse et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells

Perry

Lahiri²,

Chen³

et al. 2002

J Pharmacol Exp Ther

268

236

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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.

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Section: Discussionmentioning

confidence: 99%

“…Although predominantly located in pancreatic islets, recent reports have shown GLP-1 receptor expression in lung and brain (Kanse et al, 1988;Thorens, 1992;Campos et al, 1994). A CNS role for GLP-1 has been established from considerable experimental data showing that intracerebroventricular infusion of GLP-1 inhibits feeding in rats (Turton et al, 1996).…”

mentioning

confidence: 99%

A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells

Perry

Lahiri²,

Chen³

et al. 2002

J Pharmacol Exp Ther

268

236

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“…Furthermore, high affinity receptors for GLP-l(7-36) amide were identified in rat brain [27,83]. The distribution of receptors corresponds to the distribution of GLP-1-like immunoreactivity, with the exception of the pituitary gland.…”

Section: Glp-1 and Central Nervous Systemmentioning

confidence: 90%

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Göke

Fehmann

Göke

1991

Eur J Clin Investigation

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“…In the rat brain, GLP-1 immunoreactive cell bodies and nerve ®bres are found in areas of the brain that receive afferents from the gastrointestinal tract via the vagal nerves and control food intake. 3,4,5,6 Intracerebroventricular (ICV) injection of GLP-1 in rodents, inhibits food intake. 7 ± 9 In addition, central administration of GLP-1 has been shown to inhibit the intake of water.…”

Section: Introductionmentioning

confidence: 99%

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.

et al. 1999

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BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol Á kg 71 Á min 71 ) or saline. SUBJECTS: Eight obese (body mass index, BMI, 45.5 AE 2.3 kgam 2 ) male subjects. MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy ®xed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique. RESULTS: Hunger ratings were signi®cantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 AE 0.5 MJ (21 AE 6%) by GLP-1 infusion (P 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 AE 0.35 mmolaL; nadir: 5.3 AE 0.15 mmolaL). No nausea was recorded during GLP-1 infusion. CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this ®nding might be an increased satiety primarily mediated by gastric vagal afferent signals.

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Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung

Cited by 106 publications

References 19 publications

A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells

A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.

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