Abstract:

The ATP-generating glycolytic enzyme pyruvate kinase has been found to be a key regulator of pancreatic islet hormone secretion. This presentation will explore some of the critical roles of pyruvate kinase, including regulation of KATP channels, mitochondrial function, and insulin secretion.

Profile

Dr. Matthew Merrins is the Hoffman Professor of Cellular & Molecular Physiology at Yale University School of Medicine. The Merrins laboratory applies state of the art imaging and electrophysiological technologies to understand metabolic signaling and hormone secretion in pancreatic islet cells. As metabolic sensors for the organism, islets regulate blood glucose by releasing the hormones insulin and glucagon. A major focus of the lab is the use of fluorescence microscopy to study cellular metabolism in real time. The lab employs several different imaging modalities including widefield, confocal, spinning disk, TIRF, STED, multi-photon, and lightsheet microscopy. Using these tools, the Merrins lab uncovered the pivotal roles of pyruvate kinase and the PEP cycle in β-cell nutrient sensing and localized ATP signaling. This work has provided a quantitative description of the mechanisms that encode nutrient stimuli into the metabolic and electrical oscillations that drive pulsatile insulin secretion, and a clearer understanding of the external cues arising from the gut incretin hormones and neighboring α-cells that act via β-cell GPCRs.