Cellular and molecular biological studies on diabetes mellitus.

Our studies indicate that physiological rather than the chronological age is the important determinant of the replicative life-span of cultured cells. It is probable that excessive cellular turn-over, which can be produced by a variety of mechanisms such as excessive nutritional or hormonal stimulation, will accelerate cellular aging, with possible biological consequences. On the other hand, the biological clock appears to be intrinsic to every cell. This was shown for fibroblasts, hepatocytes, smooth muscle cells, and epidermal keratinocytes. All these cell types have a limited division potential, which is inversely proportional to the age of the donor and to the number of previous replications. On the other hand, there is a great heterogeneity in every differentiated cell line in this respect. These results in the individual capacity of every cell to express in its own inherent pathology, at different moments during its life cycle. As far as diabetes is concerned and its micro- and macro-vascular pathology, the modification of the single cell line could lead to obstructive microvascular pathology, to atherosclerotic plaques. We demonstrated that cells obtained from insulin dependent, or insulin independent diabetics can exhibit abnormal replicative capacity in vitro. Especially in adult onset diabetes, we could show the presence of a high proportion of cells, which age more rapidly than normal.(ABSTRACT TRUNCATED AT 250 WORDS)