Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy

Iichiro Shimomura, Robert E. Hammer, Shinji Ikemoto, Michael S. Brown () and Joseph L. Goldstein ()
Additional contact information
Iichiro Shimomura: Department of Molecular Genetics
Robert E. Hammer: University of Texas Southwestern Medical Center
Shinji Ikemoto: Department of Molecular Genetics
Michael S. Brown: Department of Molecular Genetics
Joseph L. Goldstein: Department of Molecular Genetics

Nature, 1999, vol. 401, issue 6748, 73-76

Abstract: Abstract Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver1. We have developed a mouse model that mimics these features of CGL2: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin2, a fat-derived hormone that regulates food intake and energy metabolism3. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.

Date: 1999
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/43448 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:401:y:1999:i:6748:d:10.1038_43448

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/43448

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().