Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion

Drs. Guofang Zhang and Mette Jensen have led studies just published online in Cell Metabolism (Dec. 14, 2020) providing novel insights into the mechanism of fuel-stimulated insulin secretion from pancreatic islet cells. Their work shows that a pathway involving counter-clockwise or reductive metabolism of glutamine in the mitochondrial TCA cycle creates metabolites that are transported to the cytosol to trigger insulin secretion. Reductive TCA cycle metabolism has previously been described as a mechanism for generating biomass in growing cancer cells, but this is the first description of the pathway as a mechanism for endocrine signaling. Other DMPI fellows and faculty who contributed as co-authors of the paper include Sarah Gray, Kimberly El, You Wang, Danhong Lu, Tom Becker, Jonathan Campbell, and Chris Newgard. Nice work team!