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. 1979 Nov;76(11):5877–5881. doi: 10.1073/pnas.76.11.5877

Primary defect of insulin receptors in skin fibroblasts cultured from an infant with leprechaunism and insulin resistance.

E E Schilling, M M Rechler, C Grunfeld, A M Rosenberg
PMCID: PMC411755  PMID: 293690

Abstract

Insulin binding to insulin receptors, on skin fibroblasts established in culture from an infant with insulin resistance and clinical features of leprechaunism was markedly decreased in comparison with cultures from an age-matched control. By contrast, the binding of epidermal growth factor, a polypeptide growth factor chemically unrelated to insulin, to patient's and control fibroblasts was indistinguishable. The selective defect in insulin binding to patient's fibroblasts was reflected in an impaired ability of insulin to stimulate 2-deoxyglucose uptake. These results most likely indicate a primary genetic defect of insulin receptors.

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Selected References

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  1. Amrhein J. A., Klingensmith G. J., Walsh P. C., McKusick V. A., Migeon C. J. Partial androgen insensitivity: the Reifenstein syndrome revisited. N Engl J Med. 1977 Aug 18;297(7):350–356. doi: 10.1056/NEJM197708182970703. [DOI] [PubMed] [Google Scholar]
  2. Bar R. S., Gorden P., Roth J., Kahn C. R., De Meyts P. Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients: effects of starvation, refeeding, and dieting. J Clin Invest. 1976 Nov;58(5):1123–1135. doi: 10.1172/JCI108565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bar R. S., Levis W. R., Rechler M. M., Harrison L. C., Siebert C., Podskalny J., Roth J., Muggeo M. Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. N Engl J Med. 1978 May 25;298(21):1164–1171. doi: 10.1056/NEJM197805252982103. [DOI] [PubMed] [Google Scholar]
  4. Brown M. S., Goldstein J. L. Familial hypercholesterolemia: A genetic defect in the low-density lipoprotein receptor. N Engl J Med. 1976 Jun 17;294(25):1386–1390. doi: 10.1056/NEJM197606172942509. [DOI] [PubMed] [Google Scholar]
  5. Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cassidy M., Fowlkes B. J., Herman C. J. Electronic cell volume (coulter volume) distribution of vaginal-cervical cytology samples. Acta Cytol. 1975 Mar-Apr;19(2):117–125. [PubMed] [Google Scholar]
  7. D'Ercole A. J., Underwood L. E., Groelke J., Plet A. Leprechaunism: studies of the relationship among hyperinsulinism, insulin resistance, and growth retardation. J Clin Endocrinol Metab. 1979 Mar;48(3):495–502. doi: 10.1210/jcem-48-3-495. [DOI] [PubMed] [Google Scholar]
  8. DONOHUE W. L., UCHIDA I. Leprechaunism: a euphemism for a rare familial disorder. J Pediatr. 1954 Nov;45(5):505–519. doi: 10.1016/s0022-3476(54)80113-2. [DOI] [PubMed] [Google Scholar]
  9. Dekaban A. Metabolic and chromosomal studies in leprechaunism. Arch Dis Child. 1965 Dec;40(214):632–636. doi: 10.1136/adc.40.214.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dodge J. A., Laurence K. M. Congenital absence of islets of Langerhans. Arch Dis Child. 1977 May;52(5):411–413. doi: 10.1136/adc.52.5.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Flier J. S., Kahn C. R., Roth J., Bar R. S. Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance. Science. 1975 Oct 3;190(4209):63–65. doi: 10.1126/science.170678. [DOI] [PubMed] [Google Scholar]
  12. Griffin J. E., Punyashthiti K., Wilson J. D. Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance. J Clin Invest. 1976 May;57(5):1342–1351. doi: 10.1172/JCI108402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hartdegen R. G., Dogliotti M., Rabinowitz L., Bartlett R. G. Leprechaunism. Case report in a black African child. Br J Dermatol. 1975 Nov;93(5):587–591. doi: 10.1111/j.1365-2133.1975.tb02254.x. [DOI] [PubMed] [Google Scholar]
  14. Hill D. E. Effect of insulin on fetal growth. Semin Perinatol. 1978 Oct;2(4):319–328. [PubMed] [Google Scholar]
  15. Kahn C. R., Flier J. S., Bar R. S., Archer J. A., Gorden P., Martin M. M., Roth J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med. 1976 Apr 1;294(14):739–745. doi: 10.1056/NEJM197604012941401. [DOI] [PubMed] [Google Scholar]
  16. Kahn C. R., Goldfine I. D., Neville D. M., Jr, De Meyts P. Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone. Endocrinology. 1978 Oct;103(4):1054–1066. doi: 10.1210/endo-103-4-1054. [DOI] [PubMed] [Google Scholar]
  17. Kahn C. R. Membrane receptors for hormones and neurotransmitters. J Cell Biol. 1976 Aug;70(2 Pt 1):261–286. doi: 10.1083/jcb.70.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karlsson F. A., Grunfeld C., Kahn C. R., Roth J. Regulation of insulin receptors and insulin responsiveness in 3T3-L1 fatty fibroblasts. Endocrinology. 1979 May;104(5):1383–1392. doi: 10.1210/endo-104-5-1383. [DOI] [PubMed] [Google Scholar]
  19. Keenan B. S., Meyer W. J., 3rd, Hadjian A. J., Jones H. W., Migeon C. J. Syndrome of androgen insensitivity in man: absence of 5 alpha-dihydrotestosterone binding protein in skin fibroblasts. J Clin Endocrinol Metab. 1974 Jun;38(6):1143–1146. doi: 10.1210/jcem-38-6-1143. [DOI] [PubMed] [Google Scholar]
  20. Kobayashi M., Olefsky J. M., Elders J., Mako M. E., Given B. D., Schedwie H. K., Fiser R. H., Hintz R. L., Horner J. A., Rubenstein A. H. Insulin resistance due to a defect distal to the insulin receptor: demonstration in a patient with leprechaunism. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3469–3473. doi: 10.1073/pnas.75.7.3469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Muggeo M., Bar R. S., Roth J., Kahn C. R., Gorden P. The insulin resistance of acromegaly: evidence for two alterations in the insulin receptor on circulating monocytes. J Clin Endocrinol Metab. 1979 Jan;48(1):17–25. doi: 10.1210/jcem-48-1-17. [DOI] [PubMed] [Google Scholar]
  22. Muggeo M., Kahn C. R., Bar R. S., Rechler M., Flier J. S., Roth J. The underlying insulin receptor in patients with antireceptor autoantibodies: demonstration of normal binding and immunological properties. J Clin Endocrinol Metab. 1979 Jul;49(1):110–119. doi: 10.1210/jcem-49-1-110. [DOI] [PubMed] [Google Scholar]
  23. Olefsky J. M., Reaven G. M. Decreased insulin binding to lymphocytes from diabetic subjects. J Clin Invest. 1974 Dec;54(6):1323–1328. doi: 10.1172/JCI107878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oseid S., Beck-Nielsen H., Pedersen O., Sovik O. Decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy. N Engl J Med. 1977 Feb 3;296(5):245–248. doi: 10.1056/NEJM197702032960503. [DOI] [PubMed] [Google Scholar]
  25. Rechler M. M., Podskalny J. M. Insulin receptors in cultured human fibroblasts. Diabetes. 1976 Apr;25(4):250–255. doi: 10.2337/diab.25.4.250. [DOI] [PubMed] [Google Scholar]
  26. Rosenbloom A. L., Goldstein S., Yip C. C. Normal insulin binding to cultured fibroblasts from patients with lipoatrophic diabetes. J Clin Endocrinol Metab. 1977 Apr;44(4):803–806. doi: 10.1210/jcem-44-4-803. [DOI] [PubMed] [Google Scholar]
  27. Roth J. Methods for assessing immunologic and biologic properties of iodinated peptide hormones. Methods Enzymol. 1975;37:223–233. doi: 10.1016/s0076-6879(75)37018-3. [DOI] [PubMed] [Google Scholar]
  28. Summitt R. L., Favara B. E. Leprechaunism (Donohue's syndrome): a case report. J Pediatr. 1969 Apr;74(4):601–610. doi: 10.1016/s0022-3476(69)80044-2. [DOI] [PubMed] [Google Scholar]
  29. Todaro G. J., De Larco J. E., Cohen S. Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Nature. 1976 Nov 4;264(5581):26–31. doi: 10.1038/264026a0. [DOI] [PubMed] [Google Scholar]
  30. Verhoeven G. F., Wilson J. D. The syndromes of primary hormone resistance. Metabolism. 1979 Mar;28(3):253–289. doi: 10.1016/0026-0495(79)90072-6. [DOI] [PubMed] [Google Scholar]

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