This report describes diabetes mellitus type 2, susceptibility to, AKT-related. The human AKT2 gene has been implicated as a susceptibility locus for noninsulin-dependent diabetes mellitus. AKT2 is one of three related serine/threonine-protein kinases in human (the others are AKT1 and AKT3); among its many functions, AKT2 plays a role in the regulation of glucose uptake into cells. AKT2 has also been implicated in a second disease, a type of hypoinsulinemic hypoglycemia (OMIM:240900). There is a single fly gene, Dmel\Akt1, orthologous to the three AKT genes in human. Classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Akt1.
The human AKT1 gene has not been introduced into flies. A series of UAS constructs of the human Hsap\AKT2 gene, both wild-type and modified, have been introduced into flies, but have not been characterized.
Loss of function alleles of Dmel\Akt1 are lethal. Some compound heterozygous combinations survive to adulthood; they exhibit reduced body weight relative to controls and lipid content is increased relative to controls. Physical interaction(s) of the Dmel\Akt1 protein product have been described; see below and in the gene report for Akt1. Notably, interaction of Dmel\Akt1 with Dmel\trbl has been characterized in the context of this Drosophila diabetes type 2 model; see the human disease model report 'insulin pathway effects, TRIB-related' (FBhh0000822).
[updated Apr. 2020 by FlyBase; FBrf0222196]
Diabetes mellitus, type 2, also called non-insulin-dependent diabetes mellitus, occurs when cells become resistant to the effects of insulin, thus disrupting the body's ability to metabolize glucose and to properly control the amount of sugar in the blood. [from Genetics Home Reference, Diabetes; 2016.02.02]
Over time, high blood glucose can lead to serious problems such as cataracts and/or retinopathy, impaired kidney function, diabetic neuropathy, and macrovascular complications (heart attack, stroke, peripheral vascular disease). [from endocrineweb; http://www.endocrineweb.com/conditions/type-2-diabetes/type-2-diabetes-complications]
See general description, above.
AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis; over 100 substrate candidates have been reported so far. One of the functions of AKT2 is regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. [from UniProt:P31751; 2016.02.03]
Many to one: 2 human to 1 Drosophila; additional high-scoring ortholog in human is AKT3; additional lower scoring orthologs are also present in human.