GCK

Fig1. The four tested CpG sites in GCK gene.

What is GCK protein?

GCK (glucokinase) is a protein coding gene which situated on the short arm of chromosome 7 at locus 7p13. Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The GCK protein is consisted of 465 amino acids and its molecular mass is approximately 52.2 kDa.

What is the function of GCK protein?

GCK protein (glucokinase C protein) is a protein that is widely found in the liver and other tissues. Its main function is to regulate blood sugar levels. Specifically, GCK protein can promote the uptake and utilization of glucose by liver cells, thereby reducing blood sugar concentrations. In addition, GCK protein can inhibit the processes of glycogen synthesis and gluconeogenesis, further maintaining the stability of blood sugar levels. In addition to regulating blood sugar, GCK protein is involved in many other biological processes, such as fatty acid metabolism, energy metabolism, and inflammatory responses. Therefore, GCK protein is considered to be an important metabolic regulatory factor.

GCK related Signaling pathways

The signaling pathways related to GCK are primarily involved in glucose homeostasis and insulin secretion. In insulin signaling pathway, insulin activates GCK in the liver and pancreatic beta cells through the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, leading to increased glucose uptake and glycolysis. While in glucagon signaling pathway, glucagon inhibits GCK in the liver through the cAMP/protein kinase A (PKA) pathway, helping to regulate glucose production.

GCK Related Diseases

Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).

Bioapplications of GCK

Bioapplications of GCK include its potential as a therapeutic target for diabetes and metabolic disorders. Modulating GCK activity or expression could help regulate glucose metabolism and blood sugar levels. Additionally, studying GCK and its signaling pathways provides insights into the mechanisms underlying glucose homeostasis and may contribute to the development of novel treatments for metabolic diseases.