Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats

Abstract

Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic β-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNA in the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mM) and high (16.7 mM), but not at low (2 mM), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats.

Nesfatin-1 stimulates glucagon and insulin secretion and beta cell NUCB2 is reduced in human type 2 diabetic subjects

“…In further support of an insulinotropic action, Nakata et al (2011) demonstrated that nesfatin-1 stimulates insulin secretion from isolated mouse islets via L-type dependent mechanisms. Furthermore, a recent report demonstrated that insulin is elevated during an oral glucose-tolerance test (OGTT) in rats subjected to 18 h continuous infusion of nesfatin-1 (Gonzalez et al 2011a). Our present data in human islets and our in vivo data in mice together with the data in these three reports suggest that nesfatin-1 is a stimulator of insulin secretion and production.…”

Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity

“…49 Whether species differences play a role remains to be further investigated. In summary, current data clearly point towards a role of central nesfatin-1 in the regulation of food intake, whereas peripheral nesfatin-1 seems to be rather involved in the reduction of gastric motility in dogs, 50 increase of hepatic b-oxidation 49 and glucose homeostasis with an increase of glucose-stimulated insulin release from the pancreas in rats 51 and humans. 52 …”

Recent progress in research on the distribution and function of NUCB2/Nesfatin-1 in peripheral tissues [Review]

“…Additional in vivo and in vitro studies also confirmed that Nesfatin-1 increased insulin secretion and glucose elimination in mice [21,22,23]. Riva et al [21] also identified that Nesfatin-1 was present in islet β-cells, but it augmented glucagon secretion independently the concentration of glucose in vitro, meanwhile increased insulin secretion and improved glucose elimination in vivo.…”