PubMed 22275755

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM2

Title: TRPM2 Ca2+ channel regulates energy balance and glucose metabolism.

Authors: 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

Journal, date & volume: Am. J. Physiol. Endocrinol. Metab., 2012 Apr , 302, E807-16

PubMed link:

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.