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Insulin receptor tyrosine-kinase activity is altered in both muscle and adipose tissue from non-obese normoglycaemic insulin-resistant subjects

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Summary

We performed i. v. insulin tolerance test in 30 non-obese (BMI<30 male and <28 female) nondiabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (Kitt values). Then we compared the tyrosine-kinase activity of immunopurified insulin receptors (using32P-ATP and poly-glu-tyr (4∶1) from both muscle and adipose tissue in 7 of the most insulin-sensitive and 7 of the most insulin-resistant subjects. No difference was observed between the two groups in the basal (no insulin) receptor tyrosine-kinase activity from both tissues. In contrast, tyrosine-kinase activity response to insulin was significantly higher (p<0.05 by 2-way ANOVA test) in receptors from both tissues of insulin-sensitive subjects. In addition, a decreased tyrosine-kinase sensitivity to insulin was observed in muscle, but not adipose, tissue of insulin-resistant subjects (insulin ED50 being 0.87±0.05 nmol/l vs 2.03±0.07,p<0.05 in insulin-sensitive and-resistant subjects). Insulin ED50 of muscle receptor tyrosine-kinase significantly (p=0.001) correlated to both Kitt values (r=−0.79) and plasma insulin values at 120 min during OGTT (r=+0.80). Insulin receptor content, as assessed by radioimmunoassay, was similar in both muscle (7.9±1.3 and 9.2±1.9 ng/mg protein) and adipose tissue (8.2±1.3 and 7.5±1.4) of insulin-sensitive and-resistant subjects. Exon 11+ isoform of insulin receptor was similarly represented in muscle speciments from six insulin-sensitive (80±8% of total receptor content) and six resistant (78±6%) subjects. In conclusion, a defective insulin stimulation of receptor tyrosine-kinase activity is present in both muscle and adipose tissue of euglycaemic non-obese insulin-resistant subjects. This defect is, therefore, an early event in the development of insulin resistance. [Diabetologia, (1995) 38: 55–61]

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Abbreviations

NIDDM:

Non-insulin-dependent diabetes mellitus

PMSF:

p-methyl sulphonyl-fluoride

IIT:

insulin tolerance test

BSA:

bovine serum albumin

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Authors and Affiliations

  1. Cattedra di Endocrinologia e Patologia Costituzionale, Università di Catania, Catania, Italy

    G. Grasso, L. Frittitta, M. Anello & P. Russo

  2. Dipartimento, di Medicina Interna, Università di Roma “Tor Vergata”, Rome, Italy

    G. Sesti

  3. Department of Endocrinology, Ospedale Garibaldi, Piazza S.Maria di Gesu, I-95123, Catania, Italy

    V. Trischitta

Authors
  1. G. Grasso
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  2. L. Frittitta
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  3. M. Anello
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  4. P. Russo
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  5. G. Sesti
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  6. V. Trischitta
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Grasso, G., Frittitta, L., Anello, M. et al. Insulin receptor tyrosine-kinase activity is altered in both muscle and adipose tissue from non-obese normoglycaemic insulin-resistant subjects. Diabetologia 38, 55–61 (1995). https://doi.org/10.1007/BF02369353

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  • DOI: https://doi.org/10.1007/BF02369353

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