Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes

P. M. Piatti, L. D. Monti, I. Zavaroni, G. Valsecchi, C. Van Phan, S. Costa, M. Conti, E. P. Sandoli, B. Solerte, G. Pozza, A. E. Pontiroli, G. Reaven

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg.h) and glucose (4 mg/kg.min) for 150 min. The mean (±SEM) ISI [(mL kg-1min-1/pmol/L) x 103] was significantly greater in those without a family history (30.3 ± 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 ± 7.2) or impaired glucose tolerance (9.5 ± 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P <0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P <0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.

Original languageEnglish
Pages (from-to)2416-2420
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number7
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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