This report describes diabetes diabetes mellitus type 2, susceptibility to, IGF2BP-related. The human gene IGF2BP2 has been implicated as a susceptibility locus for noninsulin-dependent diabetes mellitus (MIM:125853). In a GWAS analysis, the human gene IGF2BP1 was one of twelve loci identified as strongly associated with obesity (FBrf0232660). IGF2BP2 and IGF2BP1 encode RNA-binding proteins that bind to the 5' UTRs of certain genes, including insulin-like growth factor 2 (IGF2) mRNA, and regulate their translation. The fly ortholog of IGF2BP2 and IGF2BP1 is Imp, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Imp is also orthologous to the human gene IGF2BP3.
The human Hsap\IGF2BP1 gene has been introduced into flies, but has not been characterized. As of this update, human IGF2BP2 has not been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\Imp are sluggish, exhibit severe locomotor defects, and rarely survive to adult stage. Neuronal loss of function effected by RNAi results in morphologically normal adults with hemolymph trehalose levels that are significantly higher than for controls in both a fed and starved state; lifespan is increased with normal nutrition, but reduced under starvation conditions. Physical and genetic interaction(s) of Dmel\Imp have been described; see below and in the FlyBase gene report for Imp.
[updated Oct. 2019 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]
IGF2BP2 is associated with Type 2 diabetes in multiple GWAS studies (see GWAS Catalog, below in 'External links').
IGF2BP1 is associated with body fat percentage in a GWAS study (see GWAS Catalog, below in 'External links').
IGF2BP2 and IGF2BP1 encode RNA-binding proteins that binds to the 5' UTRs of certain genes, including insulin-like growth factor 2 (IGF2) mRNA, and regulate their translation.
Many to one (3 human to 1 Drosophila). The three human genes are IGF2BP1, IGF2BP2, and IGF2BP3.
Many to one (3 human to 1 Drosophila). The three human genes are IGF2BP1, IGF2BP2, and IGF2BP3.
Many to one (3 human to 1 Drosophila). The three human genes are IGF2BP1, IGF2BP2, and IGF2BP3.
Moderate-scoring ortholog of human IGF2BP1, IGF2BP2, and IGF2BP3 (1 Drosophila to 3 human). Dmel\Imp shares 39-40% identity and 56-59% similarity with the human genes.
