In vitro control of T-lymphocyte insulin receptors by in vivo modulation of insulin

J. H. Helderman, A. O. Pietri, Philip Raskin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The mechanism for carbohydrate intolerance related to insulin resistance is under intense study. Some have suggested that environmental modulation of plasma insulin concentrations may influence cellular mechanisms that could result in diminished receptor binding and thus create insulin resistance. We have employed the T-lymphocyte model to explore this possibility. Two groups of studies were performed. In the first, relative hyperinsulinemia was created in patients with type I diabetes mellitus by means of continuous subcutaneous insulin infusion by a portable insulin infusion device. In response to an elevation of 'free' plasma insulin from 14 ± 2 to 26 ± 3 μU/ml there was a progressive fall in the number of insulin receptors that developed on freshly isolated, then lectin-treated, cultured T-lymphocytes (6552 ± 377 to 3241 ± 348 sites/cell) after 14 days of hyperinsulinemia. Neither the level of lectin stimulation, as ascertained by 3H-thymidine uptake, nor the time course of response to PHA was altered by the insulin therapy. In the second study, plasma insulin was reduced in normal-weight subjects and in nondiabetic obese subjects (nearly twice ideal body weight) by means of a 4-day fast. In response to a fall in plasma insulin of 35 ± 6 to 19 ± 3 μU/ml, insulin receptor number on freshly isolated, then cultured and stimulated, lymphocytes rose from 2796 ± 379 sites/cell to 6453 ± 893 sites/cell. Again, neither a change in lectin responsiveness nor a change in the time course of PHA response accounted for the change in these data. The relationships between the direction and magnitude of changes in in vivo plasma insulin levels in both studies were analyzed together. There was a strong (r = 0.94; P < 0.001) inverse relationship between changes in plasma insulin levels and the ultimate number of insulin receptors displayed on cultured lymphocytes. We conclude that in vivo insulin modulation is important for the regulation of the appearance of insulin receptors on cultured T-lymphocytes. Since the T-cell does not bear an insulin receptor in the circulation, the regulatory signals cannot be passed to this cell by the binding event itself. These data are not explained by a shift in a subset of lymphocytes present or by alterations in the degree of cell activation induced by PHA. The T-lymphocyte capacity to synthesize insulin receptors appears to be set, in part, by ambient plasma insulin concentrations.

Original languageEnglish (US)
Pages (from-to)712-717
Number of pages6
Issue number8
StatePublished - 1983

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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