Laboratory of Matthew J. Merrins, Ph.D.

University of Wisconsin-Madison

©2014-2019 Merrins Lab

 

Current Projects

There are three isoforms of PK expressed in pancreatic beta cells – PKM1, and the dynamically regulated isoforms, PKM2 and PKLR – that convert ADP and phosphoenolpyruvate (PEP) to ATP and pyruvate. 

 
 

There are two isoforms of PK expressed in the pancreatic beta cell – PKM1, and the dynamically regulated isoform, PKM2 – which convert ADP and phosphoenolpyruvate (PEP) to ATP and pyruvate. We discovered that PKM2 amplifies insulin secretion through the mitochondrial PEP cycle. In this cycle, pyruvate generated by PK enters the mitochondria, where it can enter the TCA cycle, or be converted to oxaloacetate and leave the mitochondria as PEP.  This fate choice has profound consequences for insulin secretion, beta cell growth, and proliferation, which we are still uncovering. My group is focused on unraveling the isoform specific functions of each PK isoform.

There are two isoforms of PK expressed in the pancreatic beta cell – PKM1, and the dynamically regulated isoform, PKM2 – which convert ADP and phosphoenolpyruvate (PEP) to ATP and pyruvate. We discovered that PKM2 amplifies insulin secretion through the mitochondrial PEP cycle. In this cycle, pyruvate generated by PK enters the mitochondria, where it can enter the TCA cycle, or be converted to oxaloacetate and leave the mitochondria as PEP.  This fate choice has profound consequences for insulin secretion, beta cell growth, and proliferation, which we are still uncovering. My group is focused on unraveling the isoform specific functions of each PK isoform.