GCK

This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. 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 use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]

Glucokinase

Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (PubMed:7742312, PubMed:11916951, PubMed:15277402, PubMed:17082186, PubMed:18322640, PubMed:19146401, PubMed:25015100, PubMed:8325892).

Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (By similarity).

Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (PubMed:18322640, PubMed:25015100, PubMed:8325892, PubMed:11916951, PubMed:15277402).

Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell (By similarity).

In pancreas, plays an important role in modulating insulin secretion (By similarity).

In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (By similarity).

Required to provide D-glucose 6-phosphate for the synthesis of glycogen (PubMed:8878425).

Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:7742312).

Calcium ion import Source: Ensembl
Canonical glycolysis Source: Reactome
Cellular glucose homeostasis Source: GO_Central
Cellular response to insulin stimulus Source: BHF-UCL
Cellular response to leptin stimulus Source: BHF-UCL
Detection of glucose Source: UniProtKB
Glucose 6-phosphate metabolic process Source: UniProtKB
Glucose homeostasis Source: UniProtKB
Glycolytic process Source: GO_Central
NADP metabolic process Source: Ensembl
Negative regulation of gluconeogenesis Source: UniProtKB
Positive regulation of glycogen biosynthetic process Source: UniProtKB
Positive regulation of insulin secretion Source: UniProtKB
Regulation of glycolytic process Source: BHF-UCL
Regulation of insulin secretion Source: BHF-UCL
Regulation of potassium ion transport Source: Ensembl

Cytoplasm; Nucleus; Mitochondrion. Under low glucose concentrations, GCK associates with GCKR and the inactive complex is recruited to the hepatocyte nucleus.

Maturity-onset diabetes of the young 2 (MODY2):
A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Familial hyperinsulinemic hypoglycemia 3 (HHF3):
Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Diabetes mellitus, non-insulin-dependent (NIDDM):
A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Diabetes mellitus, permanent neonatal, 1 (PNDM1):
An autosomal recessive form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive.