Studies of vascular metabolism and diabetes

The presence and function of insulin and IGF-I receptors is studied in endothelial and vascular smooth muscle cells. Both in human endothelial cells from micro- and macro-vessels and in human vascular smooth muscle cells IGF-I receptors are several fold more abundant than insulin receptors.

We have shown that insulin and IGF-I receptors also occur as hybrid IGF-I/insulin receptors in human endothelial and vascular smooth muscle cells. The physiological and patophysiological importance of these observations are now investigated.

In clinical studies we have measured circulating IGF-I and other components of the IGF-system in patients with type 1 diabetes. In type 1 diabetic patients with long duration circulating IGF-I is 30-40% lower than in healthy controls and is not related to glycaemic control. The abnormalities in the IGF-system occur even if the patients are normoglycaemic.

We have shown that in patients with residual endogenous insulin secretion the IGF-system is almost normal while abnormalities are found in patients lacking endogenous insulin secretion. The clinical consequences of the abnormalities in the IGF-system are currently under investigation.

Our current view of the IGF-system in diabetes is shown in the figure below. Insulin deficiency in diabetes causes hyperglycaemia but also changes in the IGF-system. The delivery of insulin through the portal vein to the liver regulate growth hormone receptors and thereby IGF-I production as well as production of IGFBP-1.

Our data suggest that subcutaneous insulin treatment which is the routine used today is insufficient and that insulin delivery through the portal vein is needed to normalize the IGF-system. The IGF-I receptor is abundant in vascular cells and these cells respond to low physiological levels of IGF-I. Low circulating IGF-I may therefore be of particular importance for vascular tissue.