TRPM2 Ca 2+ channel regulates energy balance and glucose metabolism

Zhiyou Zhang, Wenyi Zhang, Dae Young Jung, Hwi Jin Ko, Yongjin Lee, Randall H. Friedline, Eunjung Lee, John Jun, Zhexi Ma, Francis Kim, Nicholas Tsitsilianos, Kathryn Chapman, Alastair Morrison, Marcus P. Cooper, Barbara A. Miller, Jason K. Kim

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42 Scopus citations

Abstract

TRPM2 Ca 2+-permeable cation channel is widely expressed and activated by markers of cellular stress. Since inflammation and stress play a major role in insulin resistance, we examined the role of TRPM2 Ca 2+ channel in glucose metabolism. A 2-h hyperinsulinemic euglycemic clamp was performed in TRPM2-deficient (KO) and wild-type mice to assess insulin sensitivity. To examine the effects of diet-induced obesity, mice were fed a high-fat diet for 4-10 mo, and metabolic cage and clamp studies were conducted in conscious mice. TRPM2-KO mice were more insulin sensitive partly because of increased glucose metabolism in peripheral organs. After 4 mo of high-fat feeding, TRPM2-KO mice were resistant to diet-induced obesity, and this was associated with increased energy expenditure and elevated expressions of PGC-1α, PGC-1β PPARα, ERRα, TFAM, and MCAD in white adipose tissue. Hyperinsulinemic euglycemic clamps showed that TRPM2-KO mice were more insulin sensitive, with increased Akt and GSK-3β phosphorylation in heart. Obesity-mediated inflammation in adipose tissue and liver was attenuated in TRPM2-KO mice. Overall, TRPM2 deletion protected mice from developing diet-induced obesity and insulin resistance. Our findings identify a novel role of TRPM2 Ca 2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.

Original languageEnglish (US)
Pages (from-to)E807-E816
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number7
DOIs
StatePublished - Apr 1 2012

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Zhang, Z., Zhang, W., Jung, D. Y., Ko, H. J., Lee, Y., Friedline, R. H., Lee, E., Jun, J., Ma, Z., Kim, F., Tsitsilianos, N., Chapman, K., Morrison, A., Cooper, M. P., Miller, B. A., & Kim, J. K. (2012). TRPM2 Ca 2+ channel regulates energy balance and glucose metabolism. American Journal of Physiology - Endocrinology and Metabolism, 302(7), E807-E816. https://doi.org/10.1152/ajpendo.00239.2011