Enzyme G6PC2’s role in regulating blood sugar levels offers new diabetes insights

A new study has uncovered a critical role for the enzyme Glucose-6-phosphatase 2 (G6PC2) in regulating blood sugar levels. The research sheds new light on how this enzyme influences glucagon secretion in pancreatic alpha (α) cells, a process crucial for maintaining healthy blood sugar levels.

The research, published in Science Translational Medicine, was led by Dr. Dana Avrahami-Tzfati from the Faculty of Medicine at Hebrew University, Dr. Benjamin Glaser from Hadassah Medical Center and Dr. Klaus H. Kaestner from the Perelman School of Medicine at the University of Pennsylvania.

Glucagon is a hormone produced by α cells in the pancreas. It works alongside insulin to regulate blood sugar levels, raising them when they drop too low. However, in people with type 2 diabetes (T2D), glucagon levels are often elevated, contributing to difficulties in controlling blood sugar.

The study provides new insights into how G6PC2, a gene associated with fasting blood sugar levels plays a role in this process. Researchers found that genetic variations in G6PC2 impact its expression in α cells. In mice lacking the G6pc2 gene specifically in α cells, glucose more effectively suppresses glucagon secretion, supporting a role for G6pc2 in regulating the suppression of glucagon secretion in response to glucose.

These findings were confirmed in human α cells, highlighting their relevance to human physiology. By demonstrating that G6PC2 helps define the “setpoint” at which glucose suppresses glucagon secretion, the study suggests new therapeutic possibilities. Targeting G6PC2 could lead to innovative treatments that address both insulin and glucagon imbalances in diabetes.

Dr. Avrahami-Tzfati highlighted the study’s broader implications: “Our findings show that the enzyme G6PC2 helps control glucagon release by sensing glucose levels in α cells. Therefore, this study offers a new therapeutic strategy of inhibiting G6PC2 to help control blood sugar in diabetics by simultaneously increasing insulin and reducing glucagon.”

Dr. Kaestner added, “This research uncovers a critical mechanism that helps maintain blood sugar balance, moving us closer to understanding the complexities of diabetes and how we can address it more effectively.”

Dr. Glaser stated, “Most current treatment approaches focus on increasing insulin levels or insulin action, without directly targeting glucagon. Inhibition of G6PC2 is different in that it targets both hormones simultaneously, potentially enhancing the therapeutic effect.”

The study provides a strong foundation for further exploration of G6PC2 as a therapeutic target, with the potential to significantly improve diabetes management.