New drug target for controlling high blood sugar discovered

Researchers have identified a new potential therapeutic target for controlling high blood sugar.

Researchers showed that lipid molecules called phosphatidic acids enhance glucose production in the liver. These findings suggest that inhibiting or reducing production of phosphatidic acids may do the opposite.

Senior author Dr. Anil Agarwal, Professor of Internal Medicine, said that their study establishes a role for phosphatidic acids in enhancing glucose production by the liver and identifies enzymes involved in the synthesis of phosphatidic acids as potential drug targets.

These observations were made while studying a mouse model of lipodystrophy, a rare metabolic disease in which the body is devoid of fat. Lipodystrophy patients often develop diabetes and accumulate fat in the liver because of an imbalance in the body's ability to properly regulate lipids and glucose.

The causal gene, AGPAT2, which is involved in the synthesis of phosphatidic acid and triglycerides, was removed in the mice, resulting in rodents with generalized lipodystrophy. The research team then examined what impact this genetic manipulation had on phosphatidic acids and glucose production.

The buildup of these lipid molecules was due to an increase in the levels of two enzymes in the liver, diacylglycerol kinase and phospholipase D. Researchers also discovered a marked increase in glucose production in the livers of the lipodystrophic mice.

The lack of normal insulin signaling in these lipodystrophic mice led to unrestricted production of phosphatidic acid, Dr. Agarwal explained, contributing to development of hyperglycemia, or high blood sugar.

The study has been published in The Journal of Biological Chemistry.