Effects of normal human insulin, insulin aspart, and insulin detemir on the lifespan of Caenorhabditis elegans

• Published in: Diabetologie und Stoffwechsel
• Main Authors: Ibrahim, Y, Schlotterer, A, Kukudov, G, Humpert, P, Rudofsky, G, Tafel, J, Hamann, A, Bierhaus, A, Nawroth, PP, Morcos, M
• Format: Conference Proceeding
• Language: English; German
• Published: 18.04.2008
• DOI: 10.1055/s-2008-1076341
• ISSN: 1861-9002

Aims: The nematode C. elegans possesses an insulin receptor which is highly homologues to the human insulin receptor and is able to bind human insulin. Hyperglycaemic culture conditions of C. elegans lead to reduction of lifespan, neuronal damage, and impairment of motility. Aim of this project was to study the effects of normal human insulin and the insulin analogues insulin aspart and insulin detemir under normal and hyperglycaemic conditions, with respect to life span and neuronal function. Methods: Wild type C. elegans were cultivated under standard and hyperglycaemic conditions, without insulin and in the presence of 10 U/ml normal insulin (Actrapid®), insulin aspart (Novorapid®), or insulin detemir (Levemir®). The effects on lifespan (Kaplan-Meier graphs), motility (video analysis of curved line (VCL) and averaged path velocity (VAP) of the animal head) were assessed. Results: Hyperglycaemic culture conditions lead to a significant reduction of lifespan ( p <0.001) and significant decreased animal motility (VCL, p <0.001, and VAP, p <0.001). Treatment with normal human insulin and insulin aspart significantly increased the lifespan of C. elegans ( p <0.01). Accordingly, hyperglycaemia-induced impairment of motility was improved by treatment with these two insulins up to 80%, p <0.01. Treatment with insulin detemir had no significant effects on lifespan and motility under hyperglycaemic conditions. Under normoglycaemic conditions we did not see a prolongation of life span or improvement of motility by any of the three insulins. Conclusion: Normal human insulin and the short acting insulin analogue insulin aspart reduces the deleterious effects of glucose in the nematode C. elegans and enhances lifespan of C. elegans under hyperglycaemic conditions, while they have no effects under normoglycaemic culture conditions. Further studies are required to evaluate the beneficial effects in C. elegans on a molecular level.