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Effect of insulin analogues on phosphatidyl inositol-3 kinase/Akt signalling in INS-1 rat pancreatic derived β-cells

Abstract Context: Insulin analogues are largely used for the treatment of diabetic patients, but concerns have been raised about their mitogenic/anti-apoptotic potential. It is therefore important to evaluate these analogues in different cell systems. Objective: The aim of this work was to establish the pharmacological profiles of insulin analogues towards PI-3 kinase/Akt pathway in INS-1 β-pancreatic cells. Methods: Bioluminescence Resonance Energy Transfer (BRET), in cell western and caspase 3/7 assays, was used to study the effects of ligands. Results: Among the five analogues evaluated, only glargine stimulated PI-3 kinase/Akt pathway with higher efficiency than insulin, whereas glargine’s metabolite M1 was less efficient. However, glargine did not show higher anti-apoptotic efficiency than insulin. Conclusion: Glargine was more efficient than insulin for the activation of PI-3 kinase/Akt pathway, but not for the inhibition of caspase 3/7 activity. Moreover, glargine’s metabolite M1 displayed lower efficiency than insulin towards PI-3 kinase/Akt activation and caspase 3/7 inhibition.