Human adipose tissue in culture V. Studies on the metabolic effects of insulin

Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphage dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G7PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PGK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.