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Diabetologia

, Volume 27, Issue 4, pp 441–446 | Cite as

Adipocyte insulin binding and insulin sensitivity in ‘brittle’ diabetes

  • R. Taylor
  • D. J. Husband
  • S. M. Marshall
  • W. M. G. Tunbridge
  • K. G. M. M. Alberti
Article

Summary

Adipocyte insulin binding and insulin sensitivity to stimulation of lipogenesis were assessed in a group of extremely ‘brittle’ diabetic patients who were resistant to subcutaneous insulin therapy and had required frequent and prolonged hospital admission. These patients had significantly lower maximum adipocyte insulin binding (1.78±0.18%) than age-, sex- and weight-matched stable diabetic control subjects (2.57±0.36%; p<0.05). Scatchard analysis suggested that the decreased binding was secondary to reduced receptor affinity with no change in receptor number. Adipocytes from the brittle subjects displayed resistance to insulin stimulation of lipogenesis compared with those from diabetic or normal control groups (half-maximal stimulation at 34±4, 15±3 and 13±2 pmol/l respectively; p<0.01 between brittle and stable diabetic groups). In the one subject who was treated with intraperitoneal insulin, the changes in insulin binding and sensitivity were found to have reverted towards normal. The peripheral tissue abnormalities of brittle diabetes may exacerbate the clinical syndrome although the relationship of these changes to the primary cause of the syndrome is uncertain.

Key words

Brittle diabetes adipocyte insulin binding insulin action intraperitoneal insulin 

References

  1. 1.
    Woodyatt RT (1937) Diabetes mellitus. In: Cecil R (ed) Textbook of medicine, 4th edn. W. B. Saunders, Philadelphia, pp 620–634Google Scholar
  2. 2.
    Tattersall R (1977) Brittle diabetes. Clin Endocrinol Metab 6: 403–419Google Scholar
  3. 3.
    Pickup JC, Williams G, Johns P, Keen H (1983) Clinical features of brittle diabetic patients unresponsive to optimised subcutaneous therapy (continuous subcutaneous insulin infusion). Diabetic Care 6: 279–284Google Scholar
  4. 4.
    Pickup JC, Home PD, Bilous RW, Keen H, Alberti KGMM (1981) Management of severely brittle diabetes by continuous subcutaneous and intramuscular insulin infusions: evidence for a defect in subcutaneous insulin absorption. Br Med J 292: 347–350Google Scholar
  5. 5.
    Home PD, Massi-Benedetti M, Gill GV, Capaldo B, Shepherd GAA, Alberti KGMM (1982) Impaired subcutaneous absorption of insulin in “brittle” diabetes. Acta Endocrinol 101: 414–420Google Scholar
  6. 6.
    Pedersen O, Hjollund E, Beck-Nielsen H, Lindskov HO, Sonne O, Gliemann J (1981) Insulin receptor and receptor mediated insulin degradation in human adipocytes. Diabetologia 20: 636–641Google Scholar
  7. 7.
    Jorgensen KH, Larsen UD (1980) Homogenous mono 125I insulins. Preparation and characterisation of mono 125I (Tyr A14) and mono 125I (Tyr A19) insulin. Diabetologia 19: 546–554Google Scholar
  8. 8.
    Gliemann J, Sonne O (1978) Binding and receptor mediated degradation of insulin in adipocytes. J Biol Chem 253: 7857–7863Google Scholar
  9. 9.
    Pedersen O, Hjollund E, Lindskov HO (1982) Insulin binding to fat and blood cells and insulin action in fat cells from young healthy males and females. Am J Physiol 243: E158–167Google Scholar
  10. 10.
    Dole VP, Meinertz H (1960) Microdetermination of long chain fatty acids in plasma tissues. J Biol Chem 235: 2575–2599Google Scholar
  11. 11.
    Hjollund E, Pedersen O, Richelsen B, Beck-Nielsen H, Sorensen NS (1983) Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high fiber diet. Metablism 32: 1067–1075Google Scholar
  12. 12.
    Ward GM, Simpson RW, Simpson HCR, Naylor BA, Mann J, Turner RC (1982) Insulin receptor binding increased by high carbohydrate low fat diet in non-insulin-dependent diabetics. Eur J Clin Invest 12: 93–96Google Scholar
  13. 13.
    Marshall S, Olefsky JM (1980) Effects of insulin internalisation, insulin binding, glucose transport and insulin degradation by isolated rat adipocytes. J Clin Invest 66: 763–772Google Scholar
  14. 14.
    Pezzino V, Vigneri R, Pliam NB, Goldfine ID (1980) Rapid regulation of plasma membrane insulin receptors. Diabetologia 19: 211–215Google Scholar
  15. 15.
    Pedersen O, Hjollund E (1982) Insulin receptors on fat and blood cells and insulin action in fat cells from patients with insulin-dependent diabetes. Diabetes 31: 706–715Google Scholar
  16. 16.
    Olefsky JM (1976) Decreased insulin binding to adipocytes and circulating monocytes from obese subjects. J Clin Invest 57: 1165–72Google Scholar
  17. 17.
    Olefsky JM, Kolterman OG, Scarlett JA (1982) Insulin action and resistance in obesity and noninsulin dependent type II diabetes mellitus. Am J Physiol 243: E15–30Google Scholar
  18. 18.
    Livingston JM, Moxley RT III (1982) Glucose ingestion mediates a rapid increase in the insulin responsiveness of rat adipocytes. Endocrinology 111: 1749–1751Google Scholar
  19. 19.
    Bar RS, Gordon P, Roth J, Kahn CR, DeMeyts P (1976) Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients. Effects of starvation, refeeding and dieting. J Clin Invest 58: 1123–1135Google Scholar
  20. 20.
    Beck-Nielsen H, Pedersen O (1978) Diurnal variation in insulin binding to human monocytes. J Clin Endo Metab 47: 385–390Google Scholar
  21. 21.
    Yasuda K, Kitabchi AE (1980) Decreased insulin binding of human erythrocytes after dexamethasone or prednisone ingestion. Diabetes 29: 811–814Google Scholar
  22. 22.
    Bratusch-Marrain PR, Smith D, DeFronzo RA (1980) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973–982Google Scholar
  23. 23.
    Beck-Nielsen H, Pedersen O, Schwartz Sorensen N (1978) Effects of diet on cellular insulin binding and the insulin sensitivity in young healthy subjects. Diabetologia 15: 289–296Google Scholar
  24. 24.
    Pedersen O, Hjollund E, Sorensen NS (1981) Insulin receptor binding and insulin action in human fat cells. Effects of obesity and fasting. Metabolism 31: 884–895Google Scholar
  25. 25.
    Kahn CR, Goldfine ID, Neville DM, DeMeyts P (1978) Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone. Endocrinology 103: 1054–1066Google Scholar
  26. 26.
    Berger M, Halban PA, Girardier L, Seydoux J, Offord RE, Renold AE (1979) Kinetics of subcutaneously injected insulin: evidence for degradation at the injection site. Diabetologia 17: 97–99Google Scholar
  27. 27.
    Pozza G, Spotti D, Micossi P, Cristallo M, Melandri M, Piatti PM, Monti LD, Pontiroli AE (1983) Long-term continuous intraperitoneal insulin treatment in brittle diabetes. Br Med J 286: 255–256Google Scholar
  28. 28.
    Schade DS, Eaton RP, Friedman NM, Spencer WJ (1980) Normalisation of plasma insulin profiles with intraperitoneal insulin infusion in diabetic man. Diabetologia 19: 35–39Google Scholar
  29. 29.
    Husband DJ, Marshall SM, Walford S, Hanning I, Wright PD, Alberti KGMM (1984) Continuous intra-peritoneal insulin infusion in the management of severely brittle diabetes — a metabolic and clinical comparison with intravenous infusion. Diabetic Med (in press)Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • R. Taylor
    • 1
  • D. J. Husband
    • 1
  • S. M. Marshall
    • 1
  • W. M. G. Tunbridge
    • 2
    • 1
  • K. G. M. M. Alberti
    • 2
  1. 1.Department of Clinical Biochemistry and Metabolic MedicineRoyal Victoria InfirmaryNewcastle upon TyneUK
  2. 2.Department of MedicineNewcastle General HospitalNewcastle upon TyneUK

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