G6PC2

G6PC2, also known as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), is a member of the glucose-6-phosphatase family of enzymes that hydrolyze glucose-6-phosphate to glucose and inorganic phosphate. The G6PC2 gene encodes a catalytic subunit–type enzyme expressed predominantly in pancreatic islets, especially insulin-producing beta cells, with little expression elsewhere.

Functionally, G6PC2 is thought to participate in the regulation of glucose-stimulated insulin secretion by modulating the intracellular pool of glucose-6-phosphate, thereby influencing glycolysis and ATP production in beta cells. This activity is believed to contribute to the glucose-sensing mechanism that links ambient glucose to insulin release. In mice, disruption of G6PC2 lowers fasting blood glucose and can alter the insulin secretory response to glucose, supporting a role in glycemic regulation, though the exact mechanisms remain under study.

Genetic variation in G6PC2 has been associated with variation in fasting blood glucose levels in humans, and common variants may influence glycemic traits without causing a monogenic disease. By contrast, G6PC2 is also a known autoantigen in type 1 diabetes; islet-infiltrating CD8+ T cells recognize IGRP, linking G6PC2 to autoimmune beta-cell targeting.

Alternate names for the gene include G6PC2 and IGRP (islet-specific glucose-6-phosphatase catalytic subunit-related protein). The gene is conserved in mammals and belongs to the broader G6PC enzyme family, which includes G6PC1 (liver) and G6PC3 (ubiquitous).