The Uab Research Foundation

Nab Research Foundation

Jeffrey Kudlow

Robert John Konrad

The present invention demonstrates a method for inhibiting O-linked protein glycosylation in a tissue or cell, comprising the step of contacting said tissue or cell with (Z)-1-&lsqb;N-(3-Ammoniopropyl)-N-(n-propyl)amino&rsqb; diazen-ium-1,2-diolate or a derivative thereof. The present invention is also directed to a method of treating or inhibiting the onset of diabetes mellitis in an individual in need of such treatment, comprising the step of admininstering to said individual a pharmacological dose of a compound which inhibiting O-linked protein glycosylation in a tissue or cell of said individual. Further, the present invention provides a pharmaceutical composition, comprising (Z)-1-&lsqb;N-(3-Ammoniopropyl)-N-(n-propyl)amino&rsqb; diazen-ium-1,2-diolate and a pharmaceutically acceptable carrier or a derivative thereof.

Method of inhibiting pancreatic &bgr;-cell p135 O-glycosylation

Standard pancreatic islet isolation results in &bgr;-cell toxicity due to nitric oxide and/or streptozotocin-like molecules that are generated during the isolation process. This toxicity can be limited by the addition of compounds that work through the glucosamine pathway in islets and/or by the addition of nitric oxide inhibitors. Unless prevented, this toxicity results in &bgr;-cells being unable to properly respond to high glucose, glucosamine, N-acetylglucosamine, or streptozotocin by increasing their relative amount of O-glycosylated protein. Likewise, in order to assess islet viability or the effect of diabetes drugs on &bgr;-cell function, islets that have been adequately protected during their isolation can be stimulated with low glucose, high glucose, glucosamine, N-acetylglucosamine, or streptozotocin with or without the drug(s) of interest present. By analyzing the pattern of islet protein O-glycosylation that occurs, one can determine whether the islets are viable and whether or not the candidate drug(s) might be useful in the treatment of diabetes.

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Birmingham, AL, United States of America

Jeffrey Kudlow