Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia

被引：271

作者：

McClain, DA

Lubas, WA

Cooksey, RC

Hazel, M

Parker, GJ

Love, DC

Hanover, JA ^{[1
]}

机构：

[1] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA

[2] Vet Affairs Med Ctr, Salt Lake City, UT 84112 USA

[3] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 16期

关键词：

D O I：

10.1073/pnas.152346899

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 resistance and beta cell toxicity are key features of type 2 diabetes. One leading hypothesis suggests that these abnormalities result from excessive flux of nutrients through the UDP-hexosamine biosynthetic pathway leading to "glucose toxicity." How the products of the hexosamine pathway mediate these effects is not known. Here, we show that transgenic overexpression of an enzyme using UDP-GlcNAc to modify proteins with O-GlcNAc produces the type 2 diabetic phenotype. Even modest overexpression of an isoform of O-GlcNAc transferase, in muscle and fat, leads to insulin resistance and hyperleptinemia. These data support the proposal that O-linked GlcNAc transferase participates in a hexosamine-dependent signaling pathway that is linked to insulin resistance and leptin production.

引用

收藏

页码：10695 / 10699

页数：5

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