TRPM2 Ca2+ channel regulates energy balance and glucose metabolism Article (Web of Science)


  • TRPM2 Ca2+-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 Ca2+ 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 Ca2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.


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

publication date

  • 2012

start page

  • E807

end page

  • E816


  • 302


  • 7