The emerging role of TRPV1 in diabetes and obesity

Trends Pharmacol Sci. 2008 Jan;29(1):29-36. doi: 10.1016/j.tips.2007.10.016. Epub 2007 Dec 4.

Abstract

The capsaicin receptor transient receptor potential vanilloid subfamily member 1 (TRPV1) is highly expressed on sensory nerve fibers innervating the pancreas. Indeed, the role of TRPV1 in mediating pain during pancreatitis is well established. The initial excitation of these nerves by capsaicin is followed by a reversible refractory state (desensitization) or, under certain conditions such as neonatal treatment, neurotoxicity. Interestingly, ablation of TRPV1-positive fibers by subcutaneous capsaicin treatment not only ameliorates pancreatitis pain but also diminishes aging-associated weight gain and improves glucose tolerance both in mice on a high-fat diet and in rat models of type 2 diabetes. New evidence implies an unexpected, pivotal role for TRPV1 in type 1 (autoimmune) diabetes. Non-obese diabetic (NOD) mice carry a hypofunctional TRPV1 mutant. Ablation of nerves carrying this mutant TRPV1 by capsaicin prevents immune-mediated destruction of islet beta cells despite the persistence of diabetogenic T cells. Collectively, these findings establish a crucial link among sensory nerves, obesity and diabetes and identify pharmacological TRPV1 blockade as a novel therapeutic approach for diabetes prevention and weight control.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Humans
  • Mice
  • Obesity / drug therapy
  • Obesity / physiopathology
  • Rats
  • TRPV Cation Channels / metabolism*

Substances

  • TRPV Cation Channels
  • TRPV1 protein, human
  • TRPV1 protein, mouse
  • TRPV1 receptor
  • Trpv1 protein, rat