Review

GLP-1, the Gut-Brain, and Brain-Periphery Axes

Cendrine Cabou, Remy Burcelin

Manuscript submitted June 30, 2011; resubmitted August 26, 2011; accepted September 5, 2011.

Keywords: type 2 diabetes, glycemic control, incretins, GLP-1, DPP-4, brain, exendin-4, glucose homeostasis, area postrema

Abstract

Glucagon-like peptide 1 (GLP-1) is a gut hormone which directly binds to the GLP-1 receptor located at the surface of the pancreatic β-cells to enhance glucose-induced insulin secretion. In addition to its pancreatic effects, GLP-1 can induce metabolic actions by interacting with its receptors expressed on nerve cells in the gut and the brain. GLP-1 can also be considered as a neuropeptide synthesized by neuronal cells in the brain stem that release the peptide directly into the hypothalamus. In this environment, GLP-1 is assumed to control numerous metabolic and cardiovascular functions such as insulin secretion, glucose production and utilization, and arterial blood flow. However, the exact roles of these two locations in the regulation of glucose homeostasis are not well understood. In this review, we highlight the latest experimental data supporting the role of the gut-brain and brain-periphery axes in the control of glucose homeostasis. We also focus our attention on the relevance of β-cell and brain cell targeting by gut GLP-1 for the regulation of glucose homeostasis. In addition to its action on β-cells, we find that understanding the physiological role of GLP-1 will help to develop GLP-1-based therapies to control glycemia in type 2 diabetes by triggering the gut-brain axis or the brain directly. This pleiotropic action of GLP-1 is an important concept that may help to explain the observation that, during their treatment, type 2 diabetic patients can be identified as 'responders' and 'non-responders'.

Fulltext: HTML , PDF (1.0 MB)

This article has been cited by other articles:

	Procyanidins and their healthy protective effects against type 2 diabetes Gonzalez-Abuin N, Pinent M, Casanova-Marti A, Arola L, Blay M, Ardevol A Curr Med Chem 2015. 22(1):39-50
	Central Nervous System Regulation of Intestinal Lipoprotein Metabolism by Glucagon-Like Peptide-1 via a Brain-Gut Axis Farr S, Baker C, Naples M, Taher J, Iqbal J, Hussain M, Adeli K Arterioscler Thromb Vasc Biol 2015. In press
	Nutraceutical oleuropein supplementation prevents high fat diet-induced adiposity in mice van der Stelt I, Hoek-van den Hil EF, Swarts HJ, Vervoort JJ, Hoving L, Skaltsounis L, Lemonakis N, Andreadou I, van Schothorst EM, Keijer J J Funct Food 2015. 14:702-715
	Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity Gong N, Xiao Q, Zhu B, Zhang CY, Wang YC, Fan H, Ma AN, Wang YX J Neurosci 2014. 34(15):5322-5334
	Incretin-based therapy and pancreatic beta cells Chon S, Riveline JP, Blondeau B, Gautier JF Diabetes Metab 2014. 40(6):411-422
	A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus Seino Y, Inagaki N, Miyahara H, Okuda I, Bush M, Ye J, Holland MC, Johnson S, Lewis E, Nakajima H Curr Med Res Opin 2014. 30(6):1095-1106
	Grape-seed procyanidins prevent the cafeteria-diet-induced decrease of glucagon-like peptide-1 production Gonzalez-Abuin N, Martinez-Micaelo N, Blay M, Ardevol A, Pinent M J Agric Food Chem 2014. 62(5):1066-1072
	Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets Wang X, Yun JW, Lei XG Antioxid Redox Signal 2014. 20(2):191-203
	GLP-1-based strategies: a physiological analysis of differential mode of action Burcelin R, Gourdy P, Dalle S Physiology (Bethesda) 2014. 29(2):108-121
	Linagliptin enhances neural stem cell proliferation after stroke in type 2 diabetic mice Darsalia V, Olverling A, Larsson M, Mansouri S, Nathanson D, Nyström T, Klein T, Sjöholm A, Patrone C Regul Pept 2014. 190-191:25-31
	Regulation of glucose homeostasis by GLP-1 Nadkarni P, Chepurny OG, Holz GG Prog Mol Biol Transl Sci 2014. 121:23-65
	Physiological and pharmacological features of GLP-1 receptor agonists in type 2 diabetes Burcelin R, Bertolini M Med Malad Metab 2013. 7(4):331-339
	GLP-1 effects on islets: hormonal, neuronal, or paracrine? Donath MY, Burcelin R Diabetes Care 2013. 36(Suppl 2):S145-S148
	Incretins: what is known, new and controversial in 2013? Burcelin R, Thorens B, European Club for the study of GLP-1 (EuCSGLP-1) Diabetes Metab 2013. 39(2):89-93
	The continuing need for drug development and clinical trials in type 2 diabetes and its complications: introduction to the RDS Special Issue Raz I, Gallwitz B Rev Diabet Stud 2011. 8(3):288-292