Transgenic mice with dominant negative PKC-theta in skeletal muscle: A new model of insulin resistance and obesity

C. Serra, M. Federici, A. Buongiorno, M. I. Senni, S. Morelli, E. Segratella, M. Pascuccio, C. Tiveron, E. Mattei, L. Tatangelo, R. Lauro, M. Molinaro, A. Giaccari, Marina Bouché

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Protein kinase C θ (PKC-θ) is the PKC isoform predominantly expressed in skeletal muscle, and it is supposed to mediate many signals necessary for muscle histogenesis and homeostasis, such as TGFβ, nerve-dependent signals and insulin. To study the role of PKC-θ in these mechanisms we generated transgenic mice expressing a "kinase dead" mutant form of PKC-θ (PKC-θK/R), working as "dominant negative," specifically in skeletal muscle. These mice are viable and fertile, however, by the 6-7 months of age, they gain weight, mainly due to visceral fat deposition. Before the onset of obesity (4 months of age), they already show increased fasting and fed insulin levels and reduced insulin-sensitivity, as measured by ipITT, but normal glucose tolerance, as measured by ipGTT. After the 6-7 months of age, transgenic mice develop hyperinsulinemia in the fasting and fed state. The ipGTT revealed in the transgenic mice both hyperglycemia and hyperinsulinemia. At the molecular level, impaired activation of the IR/IRS/PI3K pathway and a significant decrease both in the levels and in insulin-stimulated activation of the serine/threonine kinase Akt were observed. Taken together these data demonstrate that over-expression of dominant negative PKC-θ in skeletal muscle causes obesity associated to insulin resistance, as demonstrated by defective receptor and post-receptorial activation of signaling cascade.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalJournal of Cellular Physiology
Volume196
Issue number1
DOIs
Publication statusPublished - Jul 1 2003

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Protein Kinase C
Transgenic Mice
Muscle
Insulin Resistance
Skeletal Muscle
Obesity
Insulin
Hyperinsulinism
Chemical activation
Fasting
Intra-Abdominal Fat
Protein-Serine-Threonine Kinases
Mutant Proteins
Phosphatidylinositol 3-Kinases
Hyperglycemia
Weight Gain
Protein Isoforms
Homeostasis
Phosphotransferases
Glucose

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Serra, C., Federici, M., Buongiorno, A., Senni, M. I., Morelli, S., Segratella, E., ... Bouché, M. (2003). Transgenic mice with dominant negative PKC-theta in skeletal muscle: A new model of insulin resistance and obesity. Journal of Cellular Physiology, 196(1), 89-97. https://doi.org/10.1002/jcp.10278

Transgenic mice with dominant negative PKC-theta in skeletal muscle : A new model of insulin resistance and obesity. / Serra, C.; Federici, M.; Buongiorno, A.; Senni, M. I.; Morelli, S.; Segratella, E.; Pascuccio, M.; Tiveron, C.; Mattei, E.; Tatangelo, L.; Lauro, R.; Molinaro, M.; Giaccari, A.; Bouché, Marina.

In: Journal of Cellular Physiology, Vol. 196, No. 1, 01.07.2003, p. 89-97.

Research output: Contribution to journalArticle

Serra, C, Federici, M, Buongiorno, A, Senni, MI, Morelli, S, Segratella, E, Pascuccio, M, Tiveron, C, Mattei, E, Tatangelo, L, Lauro, R, Molinaro, M, Giaccari, A & Bouché, M 2003, 'Transgenic mice with dominant negative PKC-theta in skeletal muscle: A new model of insulin resistance and obesity', Journal of Cellular Physiology, vol. 196, no. 1, pp. 89-97. https://doi.org/10.1002/jcp.10278
Serra, C. ; Federici, M. ; Buongiorno, A. ; Senni, M. I. ; Morelli, S. ; Segratella, E. ; Pascuccio, M. ; Tiveron, C. ; Mattei, E. ; Tatangelo, L. ; Lauro, R. ; Molinaro, M. ; Giaccari, A. ; Bouché, Marina. / Transgenic mice with dominant negative PKC-theta in skeletal muscle : A new model of insulin resistance and obesity. In: Journal of Cellular Physiology. 2003 ; Vol. 196, No. 1. pp. 89-97.
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