Effect of insulin on weight loss and tumour growth in a cachexia model

Abstract

A comparison has been made between the effects of daily insulin injection and a ketogenic diet on weight loss and tumour weight in an experimental model of cancer cachexia (MAC16). Weight loss associated with the MAC16 tumour was significantly reduced both by a ketogenic diet (80% MCT) and by daily insulin injections without an increase in either food or water consumption. Animals fed the 80% MCT diet had a significantly reduced tumour weight compared with controls fed a normal laboratory diet, while in animals administered 20 U insulin kg-1 day-1 the tumour weight was 50% greater than in saline infused controls. The stimulation of tumour growth by insulin was counteracted by the inclusion of 3-hydroxybutyrate in the drinking water without any alteration in the extent of weight loss. Depletion of both carcass fat and muscle dry weight in animals bearing the MAC16 tumour was reversed in animals administered either insulin or an 80% MCT diet. Animals bearing the MAC16 tumour had a reduced nitrogen balance compared with non-tumour-bearing controls, mainly due to excess urea excretion, and this was reversed towards control values in animals fed an 80% MCT diet, but not in animals administered insulin. These results suggest that a ketogenic diet is more effective than insulin administration in reversing the cachectic process and has the advantage of a concomitant reduction in tumour weight.