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

被引:47
作者
Piatti, PM
Monti, LD
Zavaroni, I
Valsecchi, G
Van Phan, C
Costa, S
Conti, M
Sandoli, EP
Solerte, B
Pozza, G
Pontiroli, AE
Reaven, G
机构
[1] IRCCS H San Raffaele, Div Med, Metab Dis Unit, I-20132 Milan, Italy
[2] Univ Vita & Salute, Cattedra Clin Med Gen & Terapia Med, I-20132 Milan, Italy
[3] Univ Parma, I-43100 Parma, Italy
[4] Univ Pavia, I-27100 Pavia, Italy
[5] Stanford Univ, Sch Med, Stanford, CA 94305 USA
关键词
D O I
10.1210/jc.85.7.2416
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(-1) min(-1)/pmol/L) x 10(3)] 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.
引用
收藏
页码:2416 / 2420
页数:5
相关论文
共 28 条
[1]   Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers [J].
Albert, J ;
Wallén, NH ;
Li, NL ;
Frostell, C ;
Hjemdahl, P .
CLINICAL SCIENCE, 1999, 97 (03) :345-353
[2]   Forearm nitric oxide balance, vascular relaxation, and glucose metabolism in NIDDM patients [J].
Avogaro, A ;
Piarulli, F ;
Valerio, A ;
Miola, M ;
Calveri, M ;
Pavan, P ;
Vicini, P ;
Cobelli, C ;
Tiengo, A ;
Calo, L ;
DelPrato, S .
DIABETES, 1997, 46 (06) :1040-1046
[3]   INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION CONTRIBUTES TO BOTH INSULIN SENSITIVITY AND RESPONSIVENESS IN LEAN HUMANS [J].
BARON, AD ;
STEINBERG, HO ;
CHAKER, H ;
LEAMING, R ;
JOHNSON, A ;
BRECHTEL, G .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :786-792
[4]   SKELETAL-MUSCLE BLOOD-FLOW INDEPENDENTLY MODULATES INSULIN-MEDIATED GLUCOSE-UPTAKE [J].
BARON, AD ;
STEINBERG, H ;
BRECHTEL, G ;
JOHNSON, A .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (02) :E248-E253
[5]   The L-arginine-nitric oxide pathway: Role in atherosclerosis and therapeutic implications [J].
Boger, RH ;
BodeBoger, SM ;
Frolich, JC .
ATHEROSCLEROSIS, 1996, 127 (01) :1-11
[6]  
Catalano M, 1997, Vasc Med, V2, P302
[7]   EVIDENCE OF IMPAIRED ENDOTHELIUM-DEPENDENT CORONARY VASODILATATION IN PATIENTS WITH ANGINA-PECTORIS AND NORMAL CORONARY ANGIOGRAMS [J].
EGASHIRA, K ;
INOU, T ;
HIROOKA, Y ;
YAMADA, A ;
URABE, Y ;
TAKESHITA, A .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 328 (23) :1659-1664
[8]   INSULIN-MEDIATED VASODILATION - IMPAIRMENT WITH INCREASED BLOOD-PRESSURE AND BODY-MASS [J].
FELDMAN, RD ;
BIERBRIER, GS .
LANCET, 1993, 342 (8873) :707-709
[9]   Basal nitric oxide synthesis in essential hypertension [J].
Forte, P ;
Copland, M ;
Smith, LM ;
Milne, E ;
Sutherland, J ;
Benjamin, N .
LANCET, 1997, 349 (9055) :837-842
[10]   DEMONSTRATION OF INSULIN RESISTANCE IN UNTREATED ADULT ONSET DIABETIC SUBJECTS WITH FASTING HYPERGLYCEMIA [J].
GINSBERG, H ;
KIMMERLING, G ;
OLEFSKY, JM ;
REAVEN, GM .
JOURNAL OF CLINICAL INVESTIGATION, 1975, 55 (03) :454-461