Reduced mitogenic action of insulin evaluated as 3H-thymidine uptake in diabetic cultured fibroblasts

Abstract

As cultured diabetic fibroblasts have a shorter lifespan than normal subjects, the mitogenic activity of foetal calf serum (FCS) and insulin have been studied by taking skin biopsies from 5 patients with juvenile onset diabetes (JODM), 8 with adult onset diabetes (AODM) and 5 with chemical (latent) diabetes (CDM). In controls a high dose of insulin (20 microgram/ml) produced a tritiated thymidine uptake lower than 10% FCS. At lower doses (0.1 to 1.0 microgram/ml) a dose-dependent uptake was observed. In diabetic fibroblasts 10% FCS produced a lower 3H-thymidine uptake than in controls, with p less than 0.005 in JODM, p less than 0.01 in AODM and p less than 0.01 in CDM. A high dose of insulin produced a lower uptake in patients with JODM (p less than 0.01), AODM (p less than 0.01) and CDM (p less than 0.05) when compared with controls. However, when lower doses of insulin were used, 2 out 5 cases of JODM and 4 out of 8 cases of AODM showed a similar response to controls, while 3H-thymidine uptake was low or absent in the remaining cases, including all those with CDM. This study indicates that a reduced mitogenic action of FCS and insulin exists in many patients affected by clinical or chemical diabetes. Our results suggest, however, that the sensitivity to the two mitogenic factors seems to be dissociated: in fact, while a reduced response to FCS is present in all patients, the response to insulin seems to be correlated to the patient's equilibrium at the time of skin biopsy.