Effects of IGF-2 on glucose metabolism
S Zachariah, A Brackenbridge & D Russell Jones
The effects of IGF-2 on glucose homeostasis have been more understood from individuals with fasting hypoglycaemia associated with non-islet cell tumours. Endogenous IGFs which circulate in adults fail to exert their immense potential hypoglycaemic activity because they are largely trapped within the vascular space due to their sequestration in a high molecular weight protein complex. The tumours produce excessive amounts of big IGF-2 which is less readily bound by circulating IGFBP-3 and more available for interaction with cell surface receptors. However the exact mechanisms or effects on glucose metabolism are not well defined.
We had the opportunity to do a euglycaemic clamp study [with stable isotope infusion] on a 55 year old man who had an IGF-2 producing retroperitoneal haemangiopericytoma. He presented with recurrent hypoglycaemia [2.5 mmol/l] and was shown to have significantly raised IGF-2 levels. His C peptide and serum Insulin levels were normal. During the clamp study we measured the amount of glucose infusion needed to maintain euglycaemia, hepatic glucose production and peripheral glucose utilisation. We also looked at the effects of IGF-2 on IGFBPs, free fatty acids and counter regulatory hormones. We compared the patients results with those of normal sedentary males who also went on to have low dose [0.3 mU/kg] insulin and high dose insulin [1.5 mU/kg].
We conclude that IGF-2 leads to an increased peripheral glucose uptake in different tissues as well as inhibition of hepatic gluconeogenesis and lipolysis. We also discuss the IGF-2 effects compared to that of low dose and high dose insulin.