Metabolic Solutions Development Company announces publication of data describing potential for new drugs to maintain pancreatic beta-cells in treating diabetes
mTOT Modulators may provide a new tool for preserving beta-cell function in patients with type 2 diabetes
KALAMAZOO, Mich., May 29, 2013 /PRNewswire/ — Metabolic Solutions Development Company, LLC (MSDC) announced today the publication of data in a recent issue of the scientific journal PLOS ONE (http://dx.plos.org/10.1371/journal.pone.0062012) on the effects of a new drug for type 2 diabetes in restoring insulin sensitivity and insulin content in human beta- (b-) cells. Researchers at Washington University in St. Louis, led by Michael McDaniel, PhD, and Nidhi Rohatgi, PhD, found this next generation insulin sensitizer may provide physicians with a new tool for the treatment of diabetes that relieves insulin resistance in human islets, thereby preserving the survival and function of human beta-cells.
Beta-cells are produced in regions in the pancreas referred to as “islets”. Their function is to produce, store and release insulin, a hormone essential to the efficient utilization of glucose, a type of sugar that comes from carbohydrate foods and that is the body’s main source of energy. In patients with type 2 diabetes, beta-cell death is increased and the number of beta-cells is reduced. In addition, their function may have declined by as much as 80 percent by the time treatment is initiated, resulting in lower insulin levels and higher glucose levels. In this laboratory study, researchers found that direct treatment of cultured human islets with a new drug for the treatment of type 2 diabetes, MSDC-0160, produced a unique modulation of nutrient sensors that restored normal cell communication mechanisms and enabled the survival and preservation of human beta-cell function, including insulin content.
Diabetes is an undertreated global epidemic affecting an estimated 340 million people worldwide, with a rapidly increasing incidence throughout the developed and developing world. In the United States alone, nearly 26 million adults and children live with the disease. An additional 79 million have pre-diabetes, placing them at increased risk for developing type 2 diabetes. Recently published research by the American Diabetes Association estimates the total costs of diagnosed diabetes have risen to $245 billion in 2012 from $174 billion in 2007, when the cost was last examined. This figure represents a 41 percent increase over a five-year period.
MSDC-0160, a prototype mTOT modulator developed by MSDC, exerts its insulin sensitizing effects through a recently identified mitochondrial protein complex called mTOT(TM) (mitochondrial target of thiazolidinediones). Data suggest mTOT functions as a molecular sensor switch that coordinates carbohydrate, lipid, and amino acid metabolism with cell function. In addition to preserving beta-cell function as observed in human islets, mTOT modulators have been shown in animal models of type 2 diabetes to improve insulin signaling, decrease calorie-storing “white fat,” and increase levels of calorie burning “brown fat.”
Recently published Phase 2b clinical data from a study in 258 type 2 diabetic patients further demonstrate modulating mTOT could constitute a new approach for the discovery and development of potentially more useful and novel insulin sensitizers.
About Metabolic Solutions Development Company
Metabolic Solutions Development Company (www.msdrx.com) is a drug discovery and development company investigating novel molecular targets and developing new therapeutics to treat metabolic diseases associated with age-related mitochondrial dysfunction, especially type 2 diabetes.
 DeFronzo, RA. Diabetes, Vol. 58, April 2009, pp. 773-795.
 http://dx.plos.org/10.1371/journal.pone.0061551: “Identification of a Mitochondrial Target of Thiazolidinedione Insulin Sensitizers (mTOT) – relationship to newly identified mitochondrial pyruvate carrier proteins.”
 Colca, et al. Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer. Clinical Pharmacology & Therapeutics doi:10.1038/clpt.2013.10 .
SOURCE Metabolic Solutions Development Company, LLC