PROTECTING PANCREATIC BETA-CELLS DURING ISLET ISOLATION; ASSESSING ISLET VIABILITY AND CANDIDATE DIABETES DRUGS AFTER ISLET ISOLATION

摘要

Standard pancreatic islet isolation results in β-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 β-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 β-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-glucosylation 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.