Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice

被引：69

作者：

Longo, Kenneth A. ^{[1
]}

Charoenthongtrakul, Soratree ^{[1
]}

Giuliana, Derek J. ^{[1
]}

Govek, Elizabeth K. ^{[1
]}

McDonagh, Thomas ^{[1
]}

Qi, Yong ^{[1
]}

DiStefano, Peter S. ^{[1
]}

Geddes, Brad J. ^{[1
]}

机构：

[1] Elixir Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

REGULATORY PEPTIDES | 2008年 / 150卷 / 1-3期

关键词：

Ghrelin; Receptor; Metabolic syndrome; Diabetes; Insulin sensitivity; Metabolic flexibility;

D O I：

10.1016/j.regpep.2008.03.011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Stimulation of the ghrelin receptor (GhrR) by ghrelin results in a variety of metabolic changes including increased food intake, fat storage and insulin resistance. Loss of ghrelin signaling is protective against diet-induced obesity, suggesting that ghrelin plays a significant homeostatic role in conditions of metabolic stress. We examined glycemic control in GhrR -/- mice fed a high-fat diet, and used indirect calorimetry to assess fuel substrate usage and energy expenditure. GhrR -/- mice fed a high-fat diet had several measures of greater insulin sensitivity, including: lower fasted blood glucose and plasma insulin, lower %Hb(A1c), lower insulin levels during glucose tolerance tests, and improved performance in hyperinsulinemic-euglycemic and hyperglycemic clamp studies. GhrR -/- mice fed a high-fat diet did not develop hepatic steatosis and had lower total cholesterol, relative to controls. Furthermore, GhrR -/- mice demonstrated a lower intestinal triglyceride secretion rate of dietary lipid. GhrR -/- mice have higher respiratory quotients (RQ), indicating a preference for carbohydrate as fuel. The range of RQ values was wider in GhrR -/- mice, indicating greater metabolic flexibility and insulin sensitivity in these animals. We therefore propose that loss of ghrelin signaling promotes insulin sensitivity and metabolic flexibility, and protects against several fatty diet-induced features of metabolic syndrome due to convergent changes in the intake, absorption and utilization of energy. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：55 / 61

页数：7