Restricted replicative life-span of diabetic fibroblasts in vitro: its relation to microangiopathy

The finding that diabetic microangiopathy is caused by accumulation of multiple layers of basal lamina and experiments in which similar basal lamina layering is produced when new cell generations repopulate preexisting basal lamina scaffolding (from which previous cell generations have shed) indicate, that the rates of cell death and cell replenishment are accelerated in diabetics. Because the lesions are focal and regional and develop at different ages and in different time sequences, we have proposed that the accelerated cell turnover is probably caused by increased vulnerability of diabetic cells to injury which in turn may represent the expression of a genetically transmitted defect. To test whether this aberration can be detected in vitro, we examined the replicative life-span of skin fibroblasts from three nondiabetics, three age- and sex-matched diabetics and one individual with acquired hyperglycemia due to pancreatitis. Cells of diabetics exhibited about half the number of population doublings as cells from nondiabetics (0.01 less than P less than 0.025). Cells of the individual with pancreatitis generated a normal number of cell doublings. The interpretation that fits best with all data is that decreased replicative life span of diabetic fibroblasts in vitro is also an expression of increased susceptibility of diabetics' cells to injury and dying.