A group of researchers from the University of Wisconsin–Madison has pinpointed a gene that confers diabetes susceptibility in obese mice. Published on October 6th in the open-access journal PLoS Genetics, this study also shows that its protein tomosyn-2 acts as a brake on insulin secretion from the pancreas.
"It's too early for us to know how relevant this gene will be to human diabetes," says Alan Attie, who leads the group, "but the concept of negative regulation is one of the most interesting things to come out of this study and that very likely applies to humans."
In a properly tuned system, insulin secreted into the blood after eating helps maintain blood sugar at a safe level. Too little insulin (as in type 1 diabetes) or insulin resistance (as in type 2 diabetes) leads to high blood sugar and diabetic symptoms. Too much insulin can drive blood glucose dangerously low and lead to coma or even death. The group found tomosyn-2 while searching for genes that contribute to diabetes susceptibility in obese mice. Genetic analyses and comparisons of obese diabetes-resistant and diabetes-susceptible mouse strains revealed a single amino acid difference that destabilizes the tomosyn-2 protein in the diabetes-resistant mice, effectively releasing the brake on insulin secretion and allowing those animals to release enough insulin to avoid diabetes.
Though diabetes is highly unlikely to be caused by a single gene, identifying important biological pathways can suggest clinically useful targets. "This study shows the power of genetics to discover new mechanisms for a complex disease like type 2 diabetes," concludes Sushant Bhatnagar, a co-lead author of the paper.
FINANCIAL DISCLOSURE: This work was supported by NIDDK grants DK66369 and 58037. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Bhatnagar S, Oler AT, Rabaglia ME, Stapleton DS, Schueler KL, et al. (2011) Positional Cloning of a Type 2 Diabetes Quantitative Trait Locus; Tomosyn-2, a Negative Regulator of Insulin Secretion. PLoS Genet 7(10): e1002323. doi:10.1371/journal.pgen.1002323
CONTACT: Alan Attie
543A Biochemistry Addition
Department of Biochemistry
433 Babcock Drive
Madison, WI 53706-1544
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