Researchers discover a novel drug target linked to insulin secretion and type 2 diabetes treatment

June 2, 2014

A signal that promotes insulin secretion and reduces hyperglycemia in a type 2 diabetes animal model is enhanced by the inhibition of a novel enzyme discovered by CHUM Research Centre (CRCHUM) and University of Montreal researchers. Their study was published recently in the journal Cell Metabolism.

The secretion in the blood of insulin is dependent upon the utilization of glucose and fat by the beta-cells and the production of a novel signal that the research team discovered, named monoacylglycerol. “Despite significant research on the mechanisms implicated in insulin secretion, the signal molecules involved in this process remained enigmatic; the identification of these signals is necessary to develop better therapeutics against diabetes,” explains study co-author Marc Prentki, PhD.

“When sugar is being used by the insulin-secreting pancreatic beta-cell, it produces monoacylglycerol. We found that the production of monoacylglycerol is essential for glucose-stimulated insulin secretion by the beta-cell,” says co-author Murthy Madiraju, PhD, researcher at the CRCHUM. Importantly, the research team discovered that an enzyme called alpha/beta hydrolase domain-6 (ABHD6) breaks down monoacylglycerol and thus negatively controls insulin release.

The researchers add, “An ideal drug for type-2 diabetes would increase insulin levels in blood by enhancing the beta cells’ response to glucose only when it is elevated and also increase the sensitivity of body tissues to insulin; this is precisely what ABHD6 inhibition does, and thus we have identified a unique new target for type 2 diabetes.” The research team is currently in the process of discovering new and potent blockers of ABHD6 that do not show any unwanted toxicity and can be developed as potential drugs. Read an article summary.

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