Summary
The stimulation of glucose uptake and RNA synthesis by insulin was studied in cultured fibroblasts from patients with an inherited affinity defect of the insulin receptor. Additional cell cultures were set up of two patients with Alstrøm syndrome, a genetic disease with insulin resistance but normal insulin receptor, and of eight healthy individuals. In receptor-defective patients we found a corresponding defect of the insulin-mediated stimulation of RNA synthesis but a normal stimulation of glucose uptake. We conclude that both postreceptor effects are controlled by different insulin-directed mechanisms.
Similar content being viewed by others
References
Alstrøm CH, Hallgren B, Nilsson LB, Asander H (1959) Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness. Acta Psychiatr Neurol Scand 34 (Suppl 129):1–35
Bar RS, Muggeo M, Roth J, Kahn CR, Havrankova J, Imperato-McGinley J (1978a) Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: Evidence for a post-receptor defect. J Clin Endocrinol Metab 47:620–625
Berhanu P, Olefsky JM (1981) Effects of insulin and insulin-like agents on the glucose transport system of cultured human fibroblasts. Diabetes 30:523–529
Eckel RH, Fujimoto WY (1981) Insulin-stimulated glucose uptake, leucine incorporation into protein, and uridine incorporation into RNA in skin fibroblast cultures from patients with diabetes mellitus. Diabetologia 20:186–189
Gavin JR, Roth J, Jen P, Freychet P (1972) Insulin receptors in human circulating cells and fibroblasts. Proc Natl Acad Sci USA 69:747–751
Kahn CR, This JS, Bar RS, Archer JA, Gorden P, Martin M, Roth J (1976) The syndromes of insulin resistance and accenthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 294:739–745
Olefsky JM (1976) the insulin receptor: its role in insulin resistance of obesity and diabetes. Diabetes 25:1154–1162
Podskalny JM, Kahn RC (1982a) Cell culture studies on patients with extreme insulin resistance. I. Receptor defects on cultured fibroblasts. J Clin Endocrinol Metab 54:261–268
Podskalny JM, Kahn CR (1982b) Cell culture studies on patients with extreme insulin resistance. I. Receptor defects on cultured fibroblasts. J Clin Endocrinol Metab 54:269–275
Rüdiger HW, Dreyer M (1983) Pathogenetic mechanisms of hereditary diabetes mellitus. Hum Genet 63:100–106
Rüdiger HW, Dreyer M, Kühnau J, Bartelheimer H (1983) Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor. Hum Genet 64:407–411
Russel WC, Newman C, Williamson DH (1975) A simple cytochemical technique for demonstration of DNA in cells infected with mycoplasmas and viruses. Nature 253:461–462
Wachslicht-Rodbard H, Muggeo M, Kahn CR, Saviolakis GA, Harrison LC, Flier JS (1981) Heterogeneity of the insulin receptor interaction in lipoatrophic diabetes. J Clin Endocrinol Metab 52:416–425
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rüdiger, H.W., Ahrens, P., Dreyer, M. et al. Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor. Hum Genet 69, 76–78 (1985). https://doi.org/10.1007/BF00295533
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00295533