Skip to main content
SpringerLink
Log in

On the pathogenesis of maturity-onset diabetes mellitus

  • Published:
Acta diabetologia latina Aims and scope Submit manuscript

Conclusions

At the 6th IDF Congress in Stockholm in 1967, a hypothesis for the pathogenesis of maturity-onset diabetes under the title ‘What is inherited — what is added?’ was put forward.

Investigations over the past 10 years, on the whole, tend to confirm our concept that the capacity of the pancreatic beta-cell to respond to a standardized glucose infusion with insulin production, to a major degree, is genetically controlled. Therefore, our original idea that impaired insulin response to glucose is a marker of genetic diabetes in all its stages (prediabetes, chemical diabetes, manifest diabetes) seems plausible. Accordingly, a malfunction in the transmission of information about the blood glucose level in the extracellular fluid to those sites in the cells which regulate insulin release, would be the primary defect in genetic diabetes.

Our studies suggest that, due to increased sensitivity of the liver to insulin in the portal vein, most prediabetics retain a relatively normal — although somewhat low — glucose tolerance. This compensatory mechanism becomes insufficient and glucose intolerance is precipitated, e.g., when the demand for insulin release is increased. This occurs when the sensitivity of the body for insulin diminishes as in the case of obesity, acromegaly and pregnancy and, maybe, also during the process of aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cerasi E., Efendić S., Luft R.: Dose-response relationship of plasma insulin and blood glucose levels during oral glucose loads in prediabetic and diabetic subjects-Lanet1, 794, 1973.

  2. Cerasi E., Luft R.: Plasma insulin response to sustained hyperglycemia induced by glucose infusion in human subjects — Lancet2, 1359, 1963.

    Article  PubMed  CAS  Google Scholar 

  3. Cerasi E., Luft R.: The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus — Acta endocr. (Kbh.)55, 278, 1967.

    CAS  Google Scholar 

  4. Cerasi E., Luft R.: Insulin response to glucose infusion in diabetic and non-diabetic monozygotic twin pairs. Genetic control of insulin response? — Acta endocr. (Kbh.)55, 330, 1967.

    CAS  Google Scholar 

  5. Cerasi E., Luft R.: ‘What is inherited — what is added’ hypothesis for the pathogenesis of diabetes mellitus — Diabetes16, 615, 1967.

    PubMed  CAS  Google Scholar 

  6. Cerasi E., Luft R.: The effect of an adenosine 3′5′-monophosphate diesterase inhibitor (aminophylline) on the insulin response to glucose infusion in prediabetic and diabetic subjects — Hormone metab. Res.1, 162, 1969.

    CAS  Google Scholar 

  7. Cerasi E., Luft R.: Disappearance rate of exogenous insulin, insulin sensitivity, the response of plasma growth hormone and cortisol and urinary epinephrine to hypoglycemia in prediabetic subjects — Hormone metab. Res.1, 221, 1969.

    CAS  Google Scholar 

  8. Cerasi E., Luft R.: The pathogenesis of diabetes mellitus — a proposed concept — In:Cerasi E., Luft R. (Eds): Nobel Symposium 13: Pathogenesis of Diabetes Mellitus. Almqvist and Wiksell, Stockholm, 1970; p. 17.

    Google Scholar 

  9. Cerasi E., Luft R.: Diabetes mellitus — a disorder of cellular information transmission? — Hormone metab. Res.2, 246, 1970.

    CAS  Google Scholar 

  10. Cerasi E., Luft R.: Follow-up of non-diabetic subjects with normal and decreased insulin response to glucose infusion (first report) — Hormone metab. Res.5 (Suppl.) 113, 1974.

    CAS  Google Scholar 

  11. Cerasi E., Luft R.: Insulin secretion and the development of diabetes mellitus in the adult — In:Luft R. (Ed.): Insulin. Nordisk Insulinlaboratorium, Gentofte, Denmark, 1976; p. 123.

    Google Scholar 

  12. Cerasi E., Luft R., Efendić S.: Decreased sensitivity of the pancreatic beta-cells to glucose in prediabetic and diabetic subjects. A glucose dose-response study — Diabetes21, 224, 1972.

    PubMed  CAS  Google Scholar 

  13. Cerasi E., Luft R., Efendić S.: Effect of adrenergic blocking agents on insulin response to glucose infusion in man — Acta endocr. (Kbh.)69, 335, 1972.

    CAS  Google Scholar 

  14. Cerasi E., Wahren J., Luft R., Felig P., Hendler R.: The regulation of splanchnic glucose production in subjects with low insulin response a compensatory mechanism in prediabetes? — Europ. J. clin. Invest.3, 193, 1973.

    PubMed  CAS  Google Scholar 

  15. Deckert T., Lauridsen U., Madsen S., Mogensen P.: Insulin response to glucose, tolbutamide, secretin, and isoprenaline in maturity-onset diabetes mellitus — Dan. med. Bull.19, 222, 1972.

    PubMed  CAS  Google Scholar 

  16. Efendić S., Luft R., Cerasi E.: Quantitative evaluatio of the interaction between epinephrine and various insulin releasers in man — Diabetes, (in press).

  17. Ehrlich R. M., Randle P. J.: Serum growth-hormone concentration in diabetes mellitus — Lancet2, 233, 1961.

    Article  PubMed  CAS  Google Scholar 

  18. Gerich J. E., Charles M. A., Grodsky G. M.: Regulation of pancreatic insulin and glucagon secretion — Ann. Rev. Physiol.38, 353, 1976.

    Article  CAS  Google Scholar 

  19. Grill V., Cerasi E.: Stimulation by D-glucose of cyclic 3,5′-adenosine monophosphate accumulation and insulin release in isolated pancreatic islets of the rat — J. biol. Chem.249, 4196, 1974.

    PubMed  CAS  Google Scholar 

  20. Ikkos D., Luft R.: On the intravenous glucose tolerance test — Acta endocr. (Kbh.)25, 312, 1957.

    CAS  Google Scholar 

  21. Lindsten J., Cerasi E., Luft R., Morton N., Ryman N.: Significance of genetic factors for the plasma insulin response to glucose in healthy subjects — Clin. Genet.10, 125, 1976.

    Article  PubMed  CAS  Google Scholar 

  22. Luft R., Cerasi E., Andersson B.: Obesity as an additional factor in the pathogenesis of diabetes — Acta endocr. (Kbh.)59, 344, 1968.

    CAS  Google Scholar 

  23. Luft R., Cerasi E., Hamberger C. A.: Studies on the pathogenesis of diabetes in acromegaly — Acta endocr. (Kbh.)56, 593, 1967.

    CAS  Google Scholar 

  24. Luft R., Cerasi E., Werner S.: The effect of moderate and high doses of human growth hormone on the insulin response to glucose infusion in prediabetic subjects — Hormone metab. Res.1, 111, 1969.

    CAS  Google Scholar 

  25. Martin F. I. R., Pearson M. J., Stocks A. E.: Glucose tolerance and insulin insensitivity — Lancet1, 1285, 1968.

    Article  PubMed  CAS  Google Scholar 

  26. Price S.: Pancreatic islet cell membranes: Extraction of a possible glucoreceptor — Biochim. biophys. Acta (Amst.)318, 459, 1973.

    Article  CAS  Google Scholar 

  27. Pyke D. A., Cassar J., Todd J., Taylor K. W.: Glucose tolerance and serum insulin in identical twins of diabetics — Brit. med. J.4, 649, 1970.

    PubMed  CAS  Google Scholar 

  28. Pyke D. A., Taylor K. W.: Glucose tolerance and serum insulin in the unaffected identical twins of diabetics — Brit. med. J.4, 21, 1967.

    PubMed  CAS  Google Scholar 

  29. Robertson R. P., Porte D.: The glucose receptor: a defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor — J. clin. Invest.52, 870, 1973.

    Article  PubMed  CAS  Google Scholar 

  30. Seltzer H. S., Allen E. W., Herron A. L., Brennan M. T.: Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus — J. clin. Invest.46, 323, 1967.

    Article  PubMed  CAS  Google Scholar 

  31. Shreeve W. W., Cerasi E., Luft R.: Metabolism of (2-14C-pyruvate) in normal, acromegalic and HGH-treated human subjects — Acta endocr. (Kbh.)65, 155, 1970.

    CAS  Google Scholar 

  32. Simpson R. G., Benedetti A., Grodsky G. M., Karam J. M., Forsham P. M.: Early phase of insulin release — Diabetes17, 684, 1968.

    PubMed  CAS  Google Scholar 

  33. Tattersall R. B., Pyke D. A.: Diabetes in identical twins — Lancet,2, 1120, 1972.

    Article  PubMed  CAS  Google Scholar 

  34. Wahren J., Felig P., Cerasi E., Luft R.: Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus — J. clin. Invest.51, 1870, 1972.

    PubMed  CAS  Google Scholar 

  35. Wahren J., Felig P., Cerasi E., Luft R., Hendler R.: Splanchnic glucose production and its regulation in healthy monozygotic twins of diabetics — Clin. Sci.44, 493, 1973.

    PubMed  CAS  Google Scholar 

  36. Varsano-Aharon N., Echemendia E., Yalow R. S., Berson S. A.: Discussion — In:Cerasi E., Luft R. (Eds): Nobel Symposium 13: Pathogenesis of diabetes mellitus. Almqvist and Wiksell, Stockholm, 1970; p. 279.

    Google Scholar 

  37. Yalow R. S., Berson S.: Plasma insulin concentrations in non-diabetic and early diabetic subjects — Diabetes9, 254, 1960.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Karolinska Institutet Endokrinologiska Kliniken, Karolinska Sjukhuset, 104 01, Stockholm 60, Sweden

    Rolf Luft & Suad Efendić

Authors
  1. Rolf Luft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suad Efendić
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luft, R., Efendić, S. On the pathogenesis of maturity-onset diabetes mellitus. Acta diabet. lat 15, 1–15 (1978). https://doi.org/10.1007/BF02581002

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02581002

Key-words

Search

Navigation