Improved glucose Homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B

Mirela Delibegovic, Kendra K. Bence, Nimesh Mody, Eun-Gyoung Hong, Hwi Jin Ko, Jason K. Kim, Barbara B. Kahn, Benjamin G. Neelt

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Obesity and type 2 diabetes are characterized by insulin resistance. Mice lacking the protein-tyrosine phosphatase PTP1B in all tissues are hypersensitive to insulin but also have diminished fat stores. Because adiposity affects insulin sensitivity, the extent to which PTP1B directly regulates glucose homeostasis has been unclear. We report that mice lacking PTP1B only in muscle have body weight and adiposity comparable to those of controls on either chow or a high-fat diet (HFD). Muscle triglycerides and serum adipokines are also affected similarly by HFD in both groups. Nevertheless, muscle-specific VrPlB(-/-) mice exhibit increased muscle glucose uptake, improved systemic insulin sensitivity, and enhanced glucose tolerance. These findings correlate with and are most likely caused by increased phosphorylation of the insulin receptor and its downstream signaling components. Thus, muscle VrP1B plays a major role in regulating insulin action and glucose homeostasis, independent of adiposity. In addition, rosiglitazone treatment of HFD-fed control and muscle-specific PTPIB-/- mice revealed that rosiglitazone acts additively with PTP1B deletion. Therefore, combining PTP1B inhibition with thiazolidinediones should be more effective than either alone for treating insulin-resistant states.

Original languageEnglish
Pages (from-to)7727-7734
Number of pages8
JournalMolecular and Cellular Biology
Volume27
Issue number21
DOIs
Publication statusPublished - Nov 2007

Keywords

  • causes insulin-resistance
  • skeletal-muscle
  • negative regulator
  • meabolic syndrome
  • PTP1B
  • sensitivity
  • adiposity
  • obesity
  • lipogenesis
  • mechanisms

Cite this

Improved glucose Homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B. / Delibegovic, Mirela; Bence, Kendra K.; Mody, Nimesh; Hong, Eun-Gyoung; Ko, Hwi Jin; Kim, Jason K.; Kahn, Barbara B.; Neelt, Benjamin G.

In: Molecular and Cellular Biology, Vol. 27, No. 21, 11.2007, p. 7727-7734.

Research output: Contribution to journalArticle

Delibegovic, Mirela ; Bence, Kendra K. ; Mody, Nimesh ; Hong, Eun-Gyoung ; Ko, Hwi Jin ; Kim, Jason K. ; Kahn, Barbara B. ; Neelt, Benjamin G. / Improved glucose Homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 21. pp. 7727-7734.
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