Insulin receptor tyrosine kinase activity is reduced in monocytes from non-obese normoglycaemic insulin-resistant subjects

L. Frittitta, G. Grasso, M. E. Munguira, R. Vigneri, V. Trischitta

Research output: Contribution to journalArticlepeer-review

Abstract

Insulin sensitivity has been quantified by i. v. insulin tolerance test (0.1 U/kg of body weight) in 18 (11 male/7 female) non-obese (body mass index range 19-25 kg/m2) normoglycaemic subjects. We then compared the tyrosine kinase activity and internalization of insulin receptor in monocytes from the six most insulin-sensitive (group 1) and the six most insulin-resistant (group 3) subjects. Tyrosine kinase activity was measured on immunopurified receptors using 32P-ATP and poly-glutamic acid 4: tyrosine 1, sodium salt (poly-glu-tyr 4:1). Insulin internalization was studied by incubating cells with 1 nmol/l 125I-insulin and measuring total cell-bound and intracellular 125I-insulin by an acid dissociation procedure. Basal (in the absence of insulin) receptor kinase activity was similar in both groups. Maximal (in the presence of 100 nmol/l insulin) kinase activity was 41% lower in group 3 (13.8±3.6 fmoles 32P-ATP incorporated vs 23.3±4.0, p=0.1). Delta increment of receptor kinase activity after insulin stimulation (calculated by subtracting basal from maximal activity) was significantly (p125I-insulin were similar in the two groups. These data suggest that in non-obese, normoglycaemic subjects a defective insulin receptor tyrosine kinase activity may contribute to the development of insulin resistance. This raises the possibility that the reduced receptor kinase activity observed in Type 2 (non-insulin-dependent) diabetic patients may be independent from the diabetes and may in fact precede the appearance of the disease.

Original languageEnglish
Pages (from-to)1163-1167
Number of pages5
JournalDiabetologia
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 1993

Keywords

  • human monocytes
  • Insulin receptor
  • insulin resistance
  • internalization
  • tyrosine kinase

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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