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• W2100904495 abstract "According to the classical incretin concept, glucagon-like peptide (GLP)-1 is viewed as a hormone produced in the intestinal L cells and acting via the circulation on satiety in the brain, gut motility, and insulin and glucagon secretion in the pancreatic islet. However, in contrast to typical hormones, plasma levels of GLP-1 are relatively low with a very short half-life. Furthermore, GLP-1 is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4) in the vicinity of L cells within <1 min from the secretion of the gut peptide (1,2). This rapid metabolism of GLP-1 raises questions about how its effects are mediated on target organs such as pancreatic β-cells. In this review, we will discuss possible alternative pathways for the incretin effect on pancreatic islet. These involve L cell–derived GLP-1 via neuronal activation and α-cell–derived GLP-1 via auto/paracrine effects. Of note, GLP-1 is not acting alone, and its effect can be modulated by other factors including GIP. Since no data are available yet in the present context, we have limited this review to GLP-1.### GLP-1 in the gut-to-brain-to-periphery axis for the control of glucose metabolismRecent rodent data show that GLP-1 can induce its metabolic actions by interacting with its receptors in extrapancreatic locations such as the gut to activate the submucosal and the myenteric nervous plexi (3,4) and the brain, which then transmit the signal to peripheral tissues (5) within minutes from the absorption of glucose and lipids. The final aim of this axis is to anticipate the breakthrough of the nutrients into the blood and their better handling. Indeed, GLP-1 secreted from L cells can influence brain neuronal activities via an alternative neural pathway initiated by sensors in the hepatic portal region (6–8). Thereby, the vagus nerve transmits the metabolic information to the nucleus tractus solitarii in the brain stem, which relays the glucose signal to hypothalamic …" @default.
• W2100904495 created "2016-06-24" @default.
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• W2100904495 date "2013-07-17" @default.
• W2100904495 modified "2023-10-16" @default.
• W2100904495 title "GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine?" @default.
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• W2100904495 doi "https://doi.org/10.2337/dcs13-2015" @default.
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