Journal article
Role of PKCĪ“ in Insulin Sensitivity and Skeletal Muscle Metabolism
Diabetes (New York, N.Y.), Vol.64(12), pp.4023-4032
12/2015
DOI: 10.2337/db14-1891
PMCID: PMC4657586
PMID: 26307588
Abstract
Protein kinase C (PKC)Ī“ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCĪ“ in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKCĪ“ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCĪ“ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological levels of insulin. Likewise, in young mice, muscle-specific deletion of PKCĪ“ did not rescue high-fat diet-induced insulin resistance or glucose intolerance. However, with an increase in age, PKCĪ“ levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKCĪ“ improved whole-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCĪ“KO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCĪ“ in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCĪ“ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging.
Details
- Title: Subtitle
- Role of PKCĪ“ in Insulin Sensitivity and Skeletal Muscle Metabolism
- Creators
- Mengyao Li - Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MASara G Vienberg - Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen University, Copenhagen, DenmarkOlivier Bezy - Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MABrian T O'Neill - Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MAC Ronald Kahn - Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA c.ronald.kahn@joslin.harvard.edu
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.64(12), pp.4023-4032
- DOI
- 10.2337/db14-1891
- PMID
- 26307588
- PMCID
- PMC4657586
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- K08-DK-100543 / NIDDK NIH HHS P30 DK036836 / NIDDK NIH HHS R01 DK033201 / NIDDK NIH HHS R01-DK-033201 / NIDDK NIH HHS DK-036836 / NIDDK NIH HHS K08 DK100543 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094541102771
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