Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

被引：140

作者：

Zhang, Hua ^{[1
]}

Liu, Jingnan ^{[1
]}

Li, Caroline R. ^{[2
]}

Momen, Bahram ^{[3
]}

Kohanski, Ronald A. ^{[4
,5
]}

Pick, Leslie ^{[1
,2
]}

机构：

[1] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA

[2] Univ Maryland, Program Mol & Cell Biol, College Pk, MD 20742 USA

[3] Univ Maryland, Dept Environm Sci & Technol, College Pk, MD 20742 USA

[4] Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21205 USA

[5] Johns Hopkins Med Inst, Dept Pharmacol, Baltimore, MD 21205 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 46期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

diabetes; DILP; Drosophila insulin receptor; insect physiology; trehalose; MOUSE MODELS; LIFE-SPAN; RECEPTOR; RESISTANCE; CELL; MECHANISMS; MOSQUITO; MICE; LOCALIZATION; EXPRESSION;

D O I：

10.1073/pnas.0905083106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of "starvation in the midst of plenty,'' a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.

引用

页码：19617 / 19622

页数：6

共 52 条

[21]

Joslin EP., 2005, Joslin's diabetes mellitus, V14th

[22] Genetic modifiers of the insulin resistance phenotype in mice [J].