The human GCK gene is implicated in multiple diseases related to glucose metabolism: dominant maturity-onset diabetes of the young, type 2 (MIM:125851, FBhh0001314); recessive diabetes mellitus, permanent neonatal 1 (MIM:606176); dominant hyperinsulinemic hypoglycemia, familial, 3 (MIM:602485); and a dominant form of late-onset type 2 diabetes mellitus (MIM:125853). GCK encodes glucokinase, a member of the hexokinase family of proteins; hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. There are multiple hexokinase genes in both human and Drosophila. The fly genes most closely related to GCK are Hex-A and Hex-C.
The human GCK gene has not been introduced into flies.
GCK-related disease has been modeled in flies using RNAi-mediated knockdown of Dmel\Hex-A or Dmel\Hex-C. These two genes exhibit tissue-specific expression: Hex-A is expressed in insulin producing cells (IPCs); Hex-C is specifically expressed in the fat body. When targeted to the appropriate tissue, RNAi-mediated knockdown of Hex-A or Hex-C results in hyperglycemia, decreased body size, and impaired lipid metabolism. Hex-A is required for insulin secretion and controls Hex-C expression. In addition to glucose metabolism phenotypes, reduced levels of either Hex-A or Hex-C results in higher levels of chromosome aberrations (as assayed in larval brains); increased levels of advanced glycation end-products and reactive oxygen species (ROS) are observed.
[updated Feb. 2021 by FlyBase; FBrf0222196]
GCK encodes glucokinase, 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. Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant. [Gene Cards, GCK; 210206]
Many to many: multiple related genes in both human and Drosophila.
High-scoring ortholog of human GCK; moderate-scoring ortholog of human HK1, HK2, HK3, and HKDC1 (multiple Drosophila to multiple human). Dmel\Hex-A shares 44% identity and 63% similarity with human GCK.
High-scoring ortholog of human GCK; moderate-scoring ortholog of human HK1, HK2, HK3, and HKDC1 (multiple Drosophila to multiple human). Dmel\Hex-A shares 46% identity and 66% similarity with human GCK.
