Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk.

Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. Research Abstract Details 

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Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. Abstract Text:

Christoph Handschin,Cheol Soo Choi,Sherry Chin,Sheene Kim,Dan Kawamori,Amarnath J Kurpad,Nicole Neubauer,Jiang Hu,Vamsi K Mootha,Young-Bum Kim,Rohit N Kulkarni,Gerald I Shulman,Bruce M Spiegelman,Christoph Handschin,Cheol Soo Choi,Sherry Chin,Sheene Kim,Dan Kawamori,Amarnath J Kurpad,Nicole Neubauer,Jiang Hu,Vamsi K Mootha,Young-Bum Kim,Rohit N Kulkarni,Gerald I Shulman,Bruce M Spiegelman,

The transcriptional coactivator PPARgamma coactivator 1alpha (PGC-1alpha) is a strong activator of mitochondrial biogenesis and oxidative metabolism. While expression of PGC-1alpha and many of its mitochondrial target genes are decreased in the skeletal muscle of patients with type 2 diabetes, no causal relationship between decreased PGC-1alpha expression and abnormal glucose metabolism has been established. To address this question, we generated skeletal muscle-specific PGC-1alpha knockout mice (MKOs), which developed significantly impaired glucose tolerance but showed normal peripheral insulin sensitivity. Surprisingly, MKOs had expanded pancreatic beta cell mass, but markedly reduced plasma insulin levels, in both fed and fasted conditions. Muscle tissue from MKOs showed increased expression of several proinflammatory genes, and these mice also had elevated levels of the circulating IL-6. We further demonstrated that IL-6 treatment of isolated mouse islets suppressed glucose-stimulated insulin secretion. These data clearly illustrate a causal role for muscle PGC-1alpha in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets.

Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. Publishing Authors By Initials

C Handschin,CS Choi,S Chin,S Kim,D Kawamori,AJ Kurpad,N Neubauer,J Hu,VK Mootha,YB Kim,RN Kulkarni,GI Shulman,BM Spiegelman,C Handschin,CS Choi,S Chin,S Kim,D Kawamori,AJ Kurpad,N Neubauer,J Hu,VK Mootha,YB Kim,RN Kulkarni,GI Shulman,BM Spiegelman,

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Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 3463-74

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 2

MONTH: Nov

YEAR: 2007

Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. Information

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LANGUAGE: eng

NlmUniqueID: 7802877

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Grant and Affiliation Information for Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk.

AFFILIATION: Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: U24 DK-59635

ACRONYM: DK

MEDLINETA: J Clin Invest

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