Researchers identify new mitochondrial protein complex linked with type 2 diabetes

Researchers at Metabolic Solutions Development Company, LLC (MSDC) have identified a mitochondrial protein complex through which anti-diabetic drugs exert their insulin sensitizing effects when used to treat patients diagnosed with type 2 diabetes. Findings from this research are being presented today at the 72nd Scientific Sessions of the American Diabetes Association.

The newly identified mitochondrial protein complex is being referred to as the mitochondrial Target of Thiazolidinediones (TZDs), or mTOT^™ (ADA Abstract #1096-P).

The mTOT complex functions as a molecular "sensor switch" connecting mitochondrial metabolism to important cellular activities, such as carbohydrate, lipid, and amino acid metabolism, that are out of balance in patients with type 2 diabetes. Such imbalances may also play a role in other diseases of aging such as Alzheimer's disease and Parkinson's disease, as well certain genetic diseases such as polycystic kidney disease.

"There's a critical need to find safe insulin sensitizers that could effectively be used to treat and stop diabetes," said Jerry Colca, PhD, MSDC's co-founder, president and chief scientific officer. "This significant step forward in our understanding of the mechanism by which drugs reduce insulin resistance, combined with our recent Phase 2 clinical results, suggest that we are on the right track to realizing this goal."

Using a novel drug analog photo-catalyzable affinity probe and mass spectrometry-based proteomics, MSDC scientists identified two phylogenetically-conserved proteins in the inner mitochondrial membrane, meaning these proteins are present in, and play an important role in the development of, organisms from yeast and fruit flies to humans. Proof of identity has been demonstrated by gene expression and knockdown of expression.