Pre-clinical methods for the determination of insulin sensitivity

Judit Zsuga, Kalman Tory, Laszlo Jaszlits, Agnes Bajza, Jozsef Nemeth, Barna Peitl, Zoltan Szilvassy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We compared the hyperinsulinaemic euglycaemic glucose clamping (HEGC) procedure and the rapid insulin sensitivity test (RIST) to characterize insulin sensitivity in anaesthetized rats. The changes in insulin sensitivity were then supplemented with the direct measurement of insulin-stimulated glucose uptake using tissue accumulation of radioactive 2-deoxyglucose in skeletal muscle samples obtained from animals undergone either procedure. Studies of the recently described endogenous insulin sensitizer mechanism termed hepatic insulin sensitizing (HISS) mechanism, by the two methods yielded data for evaluation. The HISS mechanism is defined as an increase in tissue insulin sensitivity in response to post-prandial hepatic release of an undefined substance through a nitrergic pathway. For the HEGC method, insulin was infused to attain a stable plasma insulin immunoreactivity of 100 μU/ml determined by radioimmunoassay, whereas with the RIST method the HISS mechanism was activated by a 50 mg/kg i.v. insulin bolus. Euglycaemia was kept constant by means of glucose infusion. With the HEGC and the RIST methods, insulin sensitivity was defined as the average rate of glucose infusion and the amount of glucose/kg body weight/40 min (RIST index) infused to maintain euglycaemia and preinvestigation blood glucose level, respectively. During HEGC 16±4.2 mg/kg/min glucose was able to maintain euglycaemia, which decreased to 8±2.9 (p<0.05) after administration of 10 mg/kg N G-nitro-l- arginine methyl ester (l-NAME) (i.p.), a NO synthase inhibitor. Conversely, the RIST index decreased by 55±6.9% (p<0.05) after l-NAME. Similarly, 2-deoxyglucose uptake by the gastrocnemius muscle was decreased by 49.9±5.8 (p<0.05) and 52.3±7.4% (p<0.05) with the HEGC and the RIST methods, respectively. The results show that both the HEGC and the RIST methods supplemented with tissue radioactive 2-deoxyglucose uptake determinations are appropriate methods to characterize the alteration of insulin sensitivity in context of the HISS mechanism.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalJournal of biochemical and biophysical methods
Volume61
Issue number1-2 SPEC. ISS.
DOIs
Publication statusPublished - Oct 29 2004

Keywords

  • HEGC
  • HISS mechanism
  • Insulin sensitivity
  • RIST

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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