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

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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
Issue number7
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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