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Updated: Aug 30, 2026

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
Published on: June 25, 2019
[LysB3, GluB29] insulin: a novel insulin analog with enhanced beta-cell protective action
Irini Rakatzi1, Gerhard Seipke, Jürgen Eckel
1Department of Clinical Biochemistry and Pathobiochemistry, German Diabetes Research Institute, Düsseldorf, Germany.
Abstract:
Insulin receptor substrate (IRS)-2 has been implicated in the promotion of beta-cell survival. Here we tested the hypothesis that the novel analog [LysB3, GluB29] insulin (insulin glulisine, IG) might mediate an enhanced beta-cell protective effect due to its unique property of preferential IRS-2 phosphorylation. We assessed IRS activation by IG and its anti-apoptotic activity against cytokines or palmitic acid in comparison to insulin, insulin analogs, and insulin-like growth factor (IGF)-I using INS-1 cells. IG induced a prominent IRS-2 activation without significant IRS-1 stimulation. The marked cytokine- and fatty acid-induced apoptosis was strongly (55-60%) inhibited by IG both at the level of caspase 3 activation and nucleosomal release, with only 15% inhibition of apoptosis by regular insulin. At 1nM, insulin, insulin aspart, and insulin lispro were much less effective compared to IG. In conclusion, the prominent anti-apoptotic activity of insulin glulisine might serve to counteract autoimmune- and lipotoxicity-induced beta-cell destruction.
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