Cell biology as an approach to the study of the vascular complications of diabetes.

Diabetic retinopathy and macroangiopathy share the common histologic features of cellular injury and proliferation. We have studied factors in the diabetic milieu that may affect the metabolism and growth of vascular cells derived from retinal capillaries and arteries. Using cultured endothelial cells from retinal capillaries and human aorta and vascular supporting cells (pericytes and aortic smooth muscle cells), we found that the metabolism and proliferation of endothelial cells from capillaries are responsive to insulin and insulin like growth factors (IGFs). At concentrations ranging from below physiologic levels to physiologic, insulin and IGFs were additive in their effect on growth of endothelial cells from retinal capillaries. Endothelial cells from arteries were much less responsive to insulin and IGFs, although like capillary endothelium they also have high affinity receptors for these hormones. No differences in response to insulin and IGFs were observed in the vascular supporting cells. Both pericytes and arterial smooth muscle cells responded to insulin and IGFs. The effect of insulin and IGFs was also additive with other growth factors tested, including platelet-derived growth factor. Hyperglycemia inhibited the growth of capillary pericytes but had no effect on other vascular cells. The results of these studies provide us with a potential explanation for the different histologic features observed in diabetic microangiopathy and macroangiopathy.