Diabetologia

, Volume 12, Issue 6, pp 563–571

Role of insulin resistance in adipose tissue and liver in the pathogenesis of endogenous hypertriglyceridaemia in man

  • A. H. Kissebah
  • S. Alfarsi
  • P. W. Adams
  • V. Wynn
Originals

DOI: 10.1007/BF01220632

Cite this article as:
Kissebah, A.H., Alfarsi, S., Adams, P.W. et al. Diabetologia (1976) 12: 563. doi:10.1007/BF01220632

Summary

Studies were performed to evaluate the relative importance of enhanced adipose tissue lipolysis and increased insulin levels in modulating hepatic VLDL production in patients with endogenous hypertriglyceridaemia. Eight control subjects and nine patients with hypertriglyceridaemia were investigated. The latter group comprised four patients with idiopathic hypertriglyceridaemia, three maturity onset diabetics, and two siblings with diabetic lipodystrophy. Each individual's plasma VLDL was selectively labelled with I131 in the apoprotein moiety and then reinjected to assess the turnover of these molecules. This was correlated with the insulin response to an oral glucose load and with the plasma FFA flux measured by a continuous infusion of14C palmitate. In the patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics, plasma VLDL-apoprotein turnover was increased suggesting enhanced hepatic production of these molecules. Although the insulin levels in these patients were higher than normal, no significant correlation was demonstrable between the plasma insulin and the turnover of VLDL-B-apoprotein. Furthermore, in the two patients with lipo-dystrophy the turnover of plasma VLDL was within the normal range, whereas the plasma insulin responses were the highest among all the patients. These results suggest that hyperinsulinaemia alone is not sufficient to account for the increased VLDL production seen in some of our patients. The plasma FFA flux was raised in the patients with idiopathic hypertriglyceridaemia and in the maturity onset diabetics, and was within the normal range in the two patients with lipodystrophy. Indeed, in all the subjects studied a significant correlation was observed between the turnover of plasma VLDL-B-apoprotein and the plasma FFA flux. The results thus indicate that the rate of FFA release to plasma constitutes the predominant factor in determining hepatic output of VLDL and that in the majority of patients with endogenous hypertriglyceridaemia the increased FFA flux resulting from insulin resistance in adipose tissue could effectively increase VLDL production. This process appears to be independent of the prevailing insulin levels, and could occur in the presence of insulin resistance in the liver. The latter, however, could be responsible for the impaired glucose tolerance observed in some patients.

Key words

Insulin resistance endogenous hypertriglyceridaemia maturity onset diabetes diabetic lipodystrophy very low density lipoproteins (VLDL) VLDL-B-apoproteins free fatty acids (FFA) insulin 

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • A. H. Kissebah
    • 1
  • S. Alfarsi
    • 1
  • P. W. Adams
    • 1
  • V. Wynn
    • 1
  1. 1.The Alexander Simpson Laboratory for Metabolic ResearchSt. Mary's Medical SchoolLondonEngland

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