Researchers at Harvard School of Public Health (HSPH) have found a novel mechanism causing type 2 diabetes that could be targeted to prevent or treat the disease. The research highlights a previously unrecognized molecular pathway that contributes to the malfunction of liver cells in obesity, leading to insulin resistance and diabetes.

The study appears online November 24, 2014 in Nature Medicine.

“While it is well-established that obesity generates cellular and molecular stress leading to abnormal functioning of many cellular processes, the mechanisms remain incompletely understood,” said senior author Gökhan S. Hotamisligil, chair of the Department of Genetics and Complex Diseases and the Sabri Ülker Center for Nutrient, Genetic, and Metabolic Research. “Our study revealed that one of these mechanisms involves metabolic stress-induced structural changes within liver cells that compromise their function.”

The researchers used electron microscopy and other imaging techniques to view thousands of cells from the liver tissue of lean and obese mice. They counted each of the contact points between two cellular organelles — the endoplasmic reticulum (ER) and mitochondria — and demonstrated for the first time that the number of these connections, called MAMs, markedly increase during obesity.