New ways in which GLP-1 can regulate glucose homeostasis

D’Alessio, David A.; Sandoval, Darleen A.; Seeley, Randy J.

doi:10.1172/jci27207

Cited by 40 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GLP-1 is a conserved mammalian peptide produced by neuroendocrine L-cells, which can lower postprandial glucose levels in T2D by stimulating insulin production and attenuating glucagon release 199. GLP-1 also acts systemically on the pancreas, liver, heart, stomach and brain, impacting on gastric emptying, satiety and lipid absorption and metabolism 200 201. As such, a plethora of drugs have been developed as GLP-1R agonists or blockers (gliptins) of DPP-4, the enzyme that cleaves active GLP-1 in circulation 202.…”

Section: Probiotics As Diabetic Therapiesmentioning

confidence: 99%

Gut microbiota, obesity and diabetes

Patterson

Ryan

Cryan

et al. 2016

Postgraduate Medical Journal

468

281

View full text Add to dashboard Cite

The central role of the intestinal microbiota in the progression and, equally, prevention of metabolic dysfunction is becoming abundantly apparent. The symbiotic relationship between intestinal microbiota and host ensures appropriate development of the metabolic system in humans. However, disturbances in composition and, in turn, functionality of the intestinal microbiota can disrupt gut barrier function, a trip switch for metabolic endotoxemia. This low-grade chronic inflammation, brought about by the influx of inflammatory bacterial fragments into circulation through a malfunctioning gut barrier, has considerable knock-on effects for host adiposity and insulin resistance. Conversely, recent evidence suggests that there are certain bacterial species that may interact with host metabolism through metabolite-mediated stimulation of enteric hormones and other systems outside of the gastrointestinal tract, such as the endocannabinoid system. When the abundance of these keystone species begins to decline, we see a collapse of the symbiosis, reflected in a deterioration of host metabolic health. This review will investigate the intricate axis between the microbiota and host metabolism, while also addressing the promising and novel field of probiotics as metabolic therapies.

show abstract

Section: Probiotics As Diabetic Therapiesmentioning

confidence: 99%

Gut microbiota, obesity and diabetes

Patterson

Ryan

Cryan

et al. 2016

Postgraduate Medical Journal

468

281

View full text Add to dashboard Cite

show abstract

“…injection of GLP-1R antagonist exendin(9–39) results in less insulin being secreted. 142,146 Furthermore, glucose uptake and glycogen synthesis within skeletal muscle are enhanced by intragastric infusion of glucose, and this effect of glucose is blocked by exendin(9–39) delivered by the i.c.v. route.…”

Section: Glucoregulatory Properties Of Glp-1 Mediated By the Nervomentioning

confidence: 99%

“…route. 142,146 Such findings indicate that during the initial prandial state of intestinal glucose absorption, GLP-1 “primes” whole-body metabolism by acting within the brain to facilitate pancreatic insulin secretion while also enhancing skeletal muscle glucose disposal.…”

Section: Glucoregulatory Properties Of Glp-1 Mediated By the Nervomentioning

confidence: 99%

“…administration of GLP-1R agonist exendin-4 reduces blood flow and glucose uptake within skeletal muscle. 142,146 Simultaneously, insulin secretion is stimulated in order to enhance insulin-dependent hepatic glucose uptake. 142,146 Thus, in contrast to the initial prandial state of glucose absorption described earlier, GLP-1 acts in the postprandial state to shift glucose disposal from muscle to liver.…”

Section: Glucoregulatory Properties Of Glp-1 Mediated By the Nervomentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Glucose Homeostasis by GLP-1

Nadkarni

Chepurny

Holz

2014

Progress in Molecular Biology and Translational Science

216

141

View full text Add to dashboard Cite

Glucagon-like peptide-1(7–36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeo-stasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics.

show abstract

“…incretin action [45]. For those with T2DM, the β-cell response to GIP is blunted, but the response to GLP-1 is partially intact as administration of GLP-1 can improve first and late phase insulin secretion [46,47,48].…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%