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New tool identifies novel compound targeting causes of type 2 diabetes

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A new drug screening technology developed at the Harvard T.H. Chan School of Public Health has identified a new potential anti-diabetes compound — and a powerful way to quickly test whether other molecules can have a positive effect on a critical molecular pathway believed to be central to diseases ranging from diabetes to retinitis pigmentosa, cystic fibrosis, Huntington’s disease, and Alzheimer’s.

The study appears in the June 17, 2015 issue of Science Translational Medicine.

The compound, which the authors have called azoramide*, works by focusing on an organelle called the endoplasmic reticulum (ER). The ER is a tubular network within all cells where many key molecular building blocks of glucose metabolism, such as lipids and proteins, are synthesized. When someone is obese, the ER in metabolic tissues such as the liver, fat, and pancreas can no longer keep up with the demand for protein and lipid production. This results in ER stress which contributes to cellular dysfunction and the development of insulin resistance. Insulin resistance in turn makes it difficult for the body to process glucose — high blood sugar and type 2 diabetes result, as well as a cascade of other cellular malfunctions that can lead to heart and blood vessel damage.