Abnormalities in Proliferation and Protein Synthesis in Skin Fibroblast Cultures from Patients with Diabetes Mellitus

Abstract

Several aspects of in-vitro cell growth and protein synthesis were assessed in cultures of skinfibroblasts from subjects with juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM) and from age-matched nondiabetic controls (C). Ibere was an inverse correlation between increasing age and both the log-phase doubling rate and saturation density at confluence in C fibroblasts. JODM and AODM cells had a reduction in both indices of cell population growth in comparison with age-matched c fibroblasts. Fibroblasts grown in the presence of 0.3 μM hydrocortisone were stimulated to grow more rapidly and to a greater saturation density. Stimulation of cell division by hydrocortisone accentuated the abnormalities in growth of JODM and AODM fibroblasts. Total protein and collagen synthesis was measured when the fibroblasts had grown to confluency in medium with or without hydrocortisone. Hydrocortisone did not produce a significant change in total protein and collagen synthesis per cell by C fibroblasts. Fibroblasts from AODM had a 180 per cent increase in total protein and collagen synthesis in the presence of hydrocortisone. In contrast, total protein and collagen synthesis decreased 40 per cent in fibroblasts from JODM when grown in the hydrocortisone medium. These studies indicate that skin fibroblast cultures from patients with diabetes exhibit abnormalities in cell proliferation. Furthermore, hydrocortisone appears to unmask differences in protein synthesis that distinguish JODM and AODM fibroblasts in culture.