• glucose metabolism disease

This report describes a potential fly model of type 2 diabetes or related disorders using loss-of-function mutations of Dmel\Pi3K92E, which is postulated to act in the Drosophila insulin pathway. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Pi3K92E gene.

In human, there are four genes orthologous to Dmel\Pi3K92E, PIK3CD, PIK3CB, PIK3CG, and PIK3CA, which encode isoforms of the catalytic subunit of class I phosphoinositide 3-kinase (PI3K). PI3Ks are involved in multiple signaling pathways that regulate cell growth and proliferation. The human genes Hsap\PIK3CB and Hsap\PIK3CD have been introduced into flies; heterologous rescue has not been tested. The human PIK3CA gene is implicated in multiple forms of cancer (MIM:171834); see the human disease report 'cancer, multiple, PIK3C-related' (FBhh0000400).

A severe loss-of-function mutation of Dmel\Pi3K92E is a homozygous lethal. Flies with partial loss-of-function alleles have significantly reduced body weight and higher total lipid content; some alleles exhibit elevated carbohydrate levels, reduced cholinesterase activity, and impairment in retinal function. Reduced expression effected by RNAi results in cell growth defects; overexpression results in increased cell growth, size and number. Extensive genetic and physical interactions have been described for Dmel\Pi3K92E; see below and in the Pi3K92E gene report.

[updated Oct. 2019 by FlyBase; FBrf0222196]