Incretins and Amylin: Neuroendocrine Communication Between the Gut, Pancreas, and Brain in Control of Food Intake and Blood Glucose

Abstract

Arguably the most fundamental physiological systems for all eukaryotic life are those governing energy balance. Without sufficient energy, an individual is unable to survive and reproduce. Thus, an ever-growing appreciation is that mammalian physiology developed a redundant set of neuroendocrine signals that regulate energy intake and expenditure, which maintains sufficient circulating energy, predominantly in the form of glucose, to ensure that energy needs are met throughout the body. This orchestrated control requires cross-talk between the gastrointestinal tract which senses the incoming meal, the pancreas which produces glycemic counterregulatory hormones, and the brain which controls autonomic and behavioral processes regulating energy balance. Therefore, this review highlights the physiological, pharmacological, and pathophysiological effects of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), as well as the pancreatic hormone amylin, on energy balance and glycemic control.

Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance

“…As systemic administration of AmyR agonists lowers BG levels (Scherbaum, 1998) via action within the CNS (for a review, see Hayes et al, 2014;Lutz, 2005), it was important to determine whether VTA AmyR activation influences glycemia, an effect that could indirectly influence feeding. Accordingly, the effects of intra-VTA injections of sCT (0.004, 0.04, or 0.4 mg; vehicle, 100 nl) on BG were assessed in an oral glucose tolerance test.…”

Vagal mediation of GLP-1's effects on food intake and glycemia

“…The vagus nerve can mediate GLP-1 effects on post-prandial glycemia 240The interaction between autonomic nerves and incretin hormones 241 to control islet function has been conceptualized as the "neuroincretin 242 effect" [14,46,47]. Although the neuroincretin effect of GLP-1 has been 243 reviewed elsewhere[47][48][49], we aimed at reviewing both early and t1:1…”

Brain IL-6—Where Amylin and GLP-1 Antiobesity Signaling Congregate

“…Proamylin is coreleased with insulin from the b-cells after meals, and amylin decreases blood glucose (4,5). Amylin reduces food intake and body weight and potentiates effects of leptin (4-6).…”

“…5) Both decrease gastric emptying and decrease glucagon secretion, effects that could contribute to improved glucose metabolism (4,5,9). 6) In the brain, both act on the area postrema in the brain stem, but they may also act on the hypothalamus (4,5,9). However, there also differences.…”