This article is more than 5 years old. Information may no longer be current.
Gene in mice links hyperglycemia in type 2 diabetes, Down syndrome
Researchers have identified a single gene in mice that may link hyperglycemia and functional changes in beta cells in type 2 diabetes with similar insulin secretion changes often observed in Down syndrome, according to recent study findings.
Heshan Peiris, PhD, of the department of human physiology and center for neuroscience at Flinders University in Adelaide, South Australia, and colleagues developed a trisomy 21 screening method to identify genes that may be important in type 2 diabetes, using Down syndrome mouse models compared with human gene expression data from type 2 diabetes islets. The comparison identified a single gene, RCAN1, which, when overexpressed in mice, leads to abnormal mitochondria in beta cells, reduced ATP production and less insulin secretion.
“This reduced ATP availability has direct functional consequences on glucose-stimulated membrane depolarization, as well as depolarization-induced insulin exocytosis,” the researchers wrote.
Further investigation revealed that increased RCAN1 hyperpolarizes the mitochondrial membrane and blunts the respiratory output of beta-cell mitochondria, the researchers noted.
“This work goes well beyond previous findings related to the function of RCAN1 by identifying it, through an unbiased, multicenter screening approach, as a lead candidate in the control of whole body glucose metabolism and in the beta-cell dysfunction which is central in humans to the transition from insulin resistance to [type 2 diabetes],” the researchers wrote. “Such an approach could be applied to other human health disorders with phenotypes shared with [Down syndrome] individuals.”
Disclosure: The researchers report no relevant financial disclosures.