Diabetes discovery challenges known research

Yale University scientists and colleagues who used the CLS share findings that could lead to a new therapeutic approach to treating diabetes.

A discovery by an international group of scientists challenges known research on diabetes and may open the door to new therapeutic approaches for the disease that affects nearly 500 million people globally.
Their research focused on pyruvate kinase, an enzyme that is involved in communication at the cell level through a process known as protein phosphorylation, which changes the shape of a protein and alters how that protein behaves.
The study is a piece of a larger project that has researchers looking at how different signals, like insulin levels, are interpreted in the liver.
“We set out to understand and characterize insulin signalling in a laboratory model, and we found some activities in that model that were contrary to the textbooks,” said Jesse Rinehart, associate professor in the Department of Cellular & Molecular Physiology at the Yale University School of Medicine.
The team’s findings were published in Cell Reports and have opened up a new area of insight and exploration in an already highly active field of research.

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Image: Gassaway et al. identified a phosphorylation site on pyruvate kinase linking it to cyclin dependent kinase (CDK) function in the liver. This new site is part of a CDK pathway stimulated by insulin resistance in vivo. Structural and biochemical characterization reveled that pyruvate kinase phosphorylation does not alter enzymatic activity. Instead phosphorylation dictates cellular compartmentalization. This image depicts the “hand” of CDK reaching out to sequester PKL in the hepatocyte nucleus.
Credit: J. Rinehart and B. Gassaway.