Peripheral Effects of Nesfatin-1 on Glucose Homeostasis

Li, Ziru; Gao, Ling; Tang, Hong; Yin, Yue; Xiang, Xinxin; Li, Yin; Zhao, Jing; Mulholland, Michael W.; Zhang, Weizhen

doi:10.1371/journal.pone.0071513

Cited by 69 publications

(63 citation statements)

References 27 publications

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“…Our previous studies demonstrate that gastric mTOR activity is altered by changes in energy status such as fasting and obesity. Change in gastric mTOR activity affects the expression and secretion of ghrelin and nesfatin-1/ nucleobindin 2 (NUCB2), with subsequent alteration in food intake and glucose homeostasis [15][16][17][18]. Here, we present evidence that mTOR signalling regulates ileal production of GLP-1.…”

Section: Introductionmentioning

confidence: 84%

Intestinal mTOR regulates GLP-1 production in mouse L cells

Ding

et al. 2015

Diabetologia

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Aims/hypothesis Glucagon-like peptide (GLP-1), an intestinal incretin produced in L cells through proglucagon processing, is released in response to meal intake. The intracellular mechanism by which L cells sense the organism energy level to coordinate the production of GLP-1 remains unclear. Mechanistic target of rapamycin (mTOR) is an intracellular fuel sensor critical for energy homeostasis. In this study, we investigated whether intestinal mTOR regulates GLP-1 production in L cells. Methods The effects of mTOR on GLP-1 production were examined in lean-or high-fat diet (HFD) induced diabetic C57/BL6, db/db, Neurog3-Tsc1 −/− mice, and STC-1 cells.GLP-1 expression was investigated by real-time PCR and western blotting. Plasma GLP-1 and insulin were detected by enzyme immunoassay and radioimmunoassay, respectively.Results Fasting downregulated mTOR activity, which was associated with a decrement of intestinal proglucagon and circulating GLP-1. Upon re-feeding, these alterations returned to the levels of fed animals. In HFD induced diabetic mice, ileal mTOR signalling, proglucagon and circulating GLP-1 were significantly decreased. Inhibition of mTOR signalling by rapamycin decreased levels of intestinal and plasma GLP-1 in both normal and diabetic mice. Activation of the intestinal mTOR signalling by L-leucine or Tsc1 gene deletion increased levels of intestinal proglucagon and plasma GLP-1. Overexpression of mTOR stimulated proglucagon promoter activity and GLP-1 production, whereas inhibition of mTOR activity by overexpression of tuberous sclerosis 1 (TSC1) or TSC2 decreased proglucagon promoter activity and GLP-1 production in STC-1 cells. Conclusions/interpretation mTOR may link energy supply with the production of GLP-1 in L cells.

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Section: Introductionmentioning

confidence: 84%

Intestinal mTOR regulates GLP-1 production in mouse L cells

Ding

et al. 2015

Diabetologia

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“…In vivo results from rodents are more complex and thus more difficult to interpret: continuous s.c. infusion of nesfatin-1 in rodents improved glucose utilization by enhancing insulin secretion (Gonzalez et al 2011a, Li et al 2013a. At the same time, due to an activation of intracellular insulin signaling, glucose uptake is ameliorated by increasing insulin sensitivity in liver, muscle and adipose tissue of mice (Li et al 2013a).…”

Section: :1mentioning

confidence: 99%

“…At the same time, due to an activation of intracellular insulin signaling, glucose uptake is ameliorated by increasing insulin sensitivity in liver, muscle and adipose tissue of mice (Li et al 2013a). However, another study in rats could only confirm the effects on glucose uptake for the adipose tissue (Gonzalez et al 2011a) without detecting changes in insulin signal transduction (Gonzalez et al 2011a).…”

Section: :1mentioning

confidence: 99%

Nesfatin-1: functions and physiology of a novel regulatory peptide

Dore

Levata

Lehnert

et al. 2017

Journal of Endocrinology

117

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Nesfatin-1 was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. It is processed from the precursor-peptide NEFA/ nucleobindin 2 (NUCB2), which is expressed both in the central nervous system as well as in the periphery, from where it can access the brain via non-saturable transmembrane diffusion. In hypothalamus and brainstem, nesfatin-1 recruits the oxytocin, the melancortin and other systems to relay its anorexigenic properties. NUCB2/nesfatin-1 peptide expression in reward-related areas suggests that nesfatin-1 might also be involved in hedonic feeding. Besides its initially discovered anorexigenic properties, over the last years, other important functions of nesfatin-1 have been discovered, many of them related to energy homeostasis, e.g. energy expenditure and glucose homeostasis. Nesfatin-1 is not only affecting these physiological processes but also the alterations of the metabolic state (e.g. fat mass, glycemic state) have an impact on the synthesis and release of NUCB2 and/or nesfatin-1. Furthermore, nesfatin-1 exerts pleiotropic actions at the level of cardiovascular and digestive systems, as well as plays a role in stress response, behavior, sleep and reproduction. Despite the recent advances in nesfatin-1 research, a putative receptor has not been identified and furthermore potentially distinct functions of nesfatin-1 and its precursor NUCB2 have not been dissected yet. To tackle these open questions will be the major objectives of future research to broaden our knowledge on NUCB2/nesfatin-1.

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“…This efect is caused by an alteration of hepatic PEPCK/InsR/IRS-1/AMPK/AKT/ mTOR/STAT3 pathway [62,63]. In addition to the action in CNS, peripheral infusion of nesfatin-1 also signiicantly improves insulin sensitivity in the skeletal muscle, adipose tissue and liver under normal or high-fat diet condition, via altering AKT phosphorylation and GLUT4 membrane translocation [64].…”

Section: Nesfatin-1mentioning

confidence: 99%

Neuroendocrine Control of Hepatic Gluconeogenesis

Mao¹,

Zhang²

2017

Gluconeogenesis

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Glucose is intricately regulated in human body through a complex network of hormonal and neuronal factors. A series of evidence suggests that the gastrointestinal tract and the central nervous system play prominent roles in the regulation of glucose and energy homeostasis. The gut senses the nutrient supply to co-ordinate the release of hormones that activate neuronal networks in the brain, leading to the subsequent modulation of hepatic glucose output via the gut-brain-liver axis. The gut hormones also act on multiple peripheral tissues to regulate glucose level through an insulindependent and/or -independent mechanism. The brain, especially the hypothalamus, could also response to the hormones such as insulin and leptin and diferent nutrients to modulate the glucose homeostasis. In this chapter, we review the gut-brainliver axis and the role of this organ interaction in the control of glucose homeostasis. A beter understanding of these pathways will provide novel strategies for improved glycaemic control.

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Peripheral Effects of Nesfatin-1 on Glucose Homeostasis

Cited by 69 publications

References 27 publications

Intestinal mTOR regulates GLP-1 production in mouse L cells

Intestinal mTOR regulates GLP-1 production in mouse L cells

Nesfatin-1: functions and physiology of a novel regulatory peptide

Neuroendocrine Control of Hepatic Gluconeogenesis

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