Refractoriness to growth hormone is associated with increased intracellular calcium in rat adipocytes
Department of Physiology
Adipose Tissue; Animals; Calcium; Cells, Cultured; Fluorescent Dyes; Fura-2; Growth Hormone; Insulin; Male; Microscopy, Fluorescence; Oxytocin; Rats; Rats, Inbred Strains
Life Sciences | Medicine and Health Sciences
In adipocytes that have been deprived of growth hormone (GH) for at least 3 hr, GH elicits a transient insulin-like response that is followed by a period of refractoriness to further insulin-like stimulation. Exposure of adipocytes to GH in the first hour of a 3-hr incubation prevents the appearance of insulin-like sensitivity. Intracellular Ca2+ concentration [( Ca2+]i) was measured in individual adipocytes that were loaded with fura-2 hexakis(acetoxymethyl) ester after preincubation in the presence (refractory) or absence (sensitive) of recombinant human GH at 100 ng/ml. Using a dual nitrogen laser imaging microscope with computer-assisted image processing to measure fluorescence changes, we observed that resting [Ca2+]i was 220 +/- 10 nM in refractory adipocytes and 110 +/- 6 nM in sensitive adipocytes (P less than 0.001). GH had no acute effect on [Ca2+]i in sensitive adipocytes but caused a sustained 3-fold increase in [Ca2+]i in refractory cells within 3 min (P less than 0.001). Insulin did not change [Ca2+]i in either sensitive or refractory adipocytes. In refractory cells treated with insulin and GH simultaneously, insulin completely blocked the rise in [Ca2+]i due to GH. Oxytocin elicited a prompt increase in [Ca2+]i followed by a quick return to resting levels in both sensitive and refractory cells. These findings indicate that basal [Ca2+]i is increased in refractory cells and that GH produces a sustained rise in [Ca2+]i only in refractory adipocytes. We suggest that the sustained increase in [Ca2+]i produced by GH in refractory cells prevents the expression of the insulin-like response.
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6790-4.
Proceedings of the National Academy of Sciences of the United States of America
Schwartz, Yael; Goodman, H. Maurice; and Yamaguchi, Hiroshi, "Refractoriness to growth hormone is associated with increased intracellular calcium in rat adipocytes" (1991). Open Access Articles. 1826.