Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced β cell dysfunction in isolated pancreatic islets
Summary
Uncoupling protein 2 (UCP2) negatively regulates insulin secretion. UCP2 deficiency (by means of gene knockout) improves obesity- and high glucose-induced β cell dysfunction and consequently improves type 2 diabetes in mice. In the present study, we have discovered that the small molecule, genipin, rapidly inhibits UCP2-mediated proton leak. In isolated mitochondria, genipin inhibits UCP2-mediated proton leak. In pancreatic islet cells, genipin increases mitochondrial membrane potential, increases ATP levels, closes KATP channels, and stimulates insulin secretion. These actions of genipin occur in a UCP2-dependent manner. Importantly, acute addition of genipin to isolated islets reverses high glucose- and obesity-induced β cell dysfunction. Thus, genipin and/or chemically modified variants of genipin are useful research tools for studying biological processes thought to be controlled by UCP2. In addition, these agents represent lead compounds that comprise a starting point for the development of therapies aimed at treating β cell dysfunction.
On a related note, claims have been made by Dr. Eades and others, that on low carb diets a metabolic advantage is achieved at least in part by wasting fat calories because high fat diets increase uncoupling proteins in mitochondria. If true, and this impacts UCP2 in beta cells, this would not be a good thing! If I'm reading this summary correctly, excessive UCP2 "short circuits" the beta cells and keeps them from releasing insulin.
No comments:
Post a Comment