Expression of metabolic hormone signalling genes in the brain of a triprolyl-human amylin transgenic mouse model of type 2 diabetes

ABSTRACT: There is a need for greater understanding of the molecular mechanism underlying the development of insulin resistance in type 2 diabetes, and new models in which to study this. The hormone amylin is postulated to be involved in the development of this disease, as human amylin (hA) forms amyloid in the pancreases of diabetic patients, and wild-type hA oligomers have been shown to be cytotoxic to β-cells. By contrast, rodent amylin is non-amyloidogenic, so mice expressing wild-type hA have been developed. However, amylin-evoked β-cell loss in these models limits the secretion of amylin and insulin. We have developed transgenic mice that overexpress [25, 28, 29triprolyl]human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 (L44) model. These mice develop obesity and hyperglycaemia. We examined the expression of 43 genes involved in amylin, insulin and leptin signalling in the brain of this model, at different disease stages, using the NanoString nCounter (NanoString Technologies, Seattle, WA, USA). After onset of diabetes, mice remained hyperglycaemic for a period of time but blood glucose levels eventually returned to normoglycaemia. The incidence of diabetes (defined as having blood glucose measurements > 11 mM over 3 consecutive weeks) was gene-dose dependent; 81% of homozygous mice and 59% of hemizygous mice developed diabetes over 400 days. A proportion of nontransgenic mice (33%) also developed diabetes. As these were bred from hemizygous pairs this may be the result of epigenetic or environmental factors.

ORGANISM(S): Mus musculus

PROVIDER: GSE132940 | GEO | 2019/10/10

REPOSITORIES: GEO