TY - JOUR
T1 - Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes
AU - Piatti, P. M.
AU - Monti, L. D.
AU - Zavaroni, I.
AU - Valsecchi, G.
AU - Van Phan, C.
AU - Costa, S.
AU - Conti, M.
AU - Sandoli, E. P.
AU - Solerte, B.
AU - Pozza, G.
AU - Pontiroli, A. E.
AU - Reaven, G.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.85.7.2416
DO - 10.1210/jc.85.7.2416
M3 - Article
C2 - 10902787
AN - SCOPUS:17744362283
VL - 85
SP - 2416
EP - 2420
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -