• glucose metabolism disease

A number of diabetic syndromes of varying severity are associated with defects in the insulin receptor, INSR. See the OMIM report for the INSR gene (MIM:147670) and links in 'Related Diseases' for information on specific syndromes. Diabetes mellitus, noninsulin-dependent or type 2 (NIDDM, FBhh0000153) is a related disease with many implicated genes. This report describes fly disease models using Dmel\InR, the fly ortholog of INSR, for which classical hypomorphic alleles, a constitutively active dominant-negative allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\InR is also orthologous to human genes IGF1R (implicated in a growth deficiency, MIM:270450) and INSRR.

A UAS construct carrying the human Hsap\INSR gene has been introduced into flies, but has not been used in the context of an insulin resistance model.

Loss of function alleles of Dmel\InR are lethal. Some compound heterozygous combinations survive to adulthood; they exhibit reduced body weight relative to controls; lipid and carbohydrate content are increased relative to controls. Many physical interactions and genetic interactions of Dmel\InR have been described; see below and in the gene report for InR. See also Vinayagam et al., 2016 (FBrf0233454), which describes a comprehensive analysis of the InR/PI3K/AKT network in Drosophila.

Constructs carrying mutations in the fly ortholog of INSR, Dmel\InR, analogous to a human variant implicated in a severe form of insulin resistance (Donohue syndrome, FBhh0000173) have been constructed and made available. Variant(s) implicated in human disease created (as analogous mutation in fly gene): K414P in the fly InR gene (corresponds to R113P in the human INSR gene).

[updated Mar. 2020 by FlyBase; FBrf0222196]