Role of blood flow in regulating insulin-stimulated glucose uptake in humans studies using bradykinin, [O-15]water, and [F-18]fluoro-deoxy-glucose and positron emission tomography

被引:163
作者
Nuutila, P
Raitakari, M
Laine, H
Kirvela, O
Takala, T
Utriainen, T
Makimattila, S
Pitkanen, OP
Ruotsalainen, U
Iida, H
Knuuti, J
YkiJarvinen, H
机构
[1] UNIV TURKU,TURKU MED CYCLOTRON PET CTR,TURKU,FINLAND
[2] UNIV TURKU,DEPT MED,TURKU,FINLAND
[3] UNIV TURKU,DEPT NUCL MED,TURKU,FINLAND
[4] UNIV TURKU,DEPT ANESTHESIOL,TURKU,FINLAND
[5] RES INST BRAIN & BLOOD VESSELS,AKITA,JAPAN
[6] UNIV HELSINKI,DEPT MED,DIV ENDOCRINOL,HELSINKI,FINLAND
关键词
insulin sensitivity; bradykinin; tomography; imaging techniques;
D O I
10.1172/JCI118601
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Defects in insulin stimulation of blood flow have been suggested to contribute to insulin resistance, To directly test whether glucose uptake can be altered by changing blood flow, we infused bradykinin (27 mu g over 100 min), an endothelium-dependent vasodilator, into the femoral artery of 12 normal subjects (age 25+/-1 yr, body mass index 22+/-1 kg/m(2)) after an overnight fast (n = 5) and during normoglycemic hyperinsulinemic (n = 7) conditions (serum insulin 465+/-11 pmol/liter, 0-100 min). Blood flow was measured simultaneously in both femoral regions using [O-15]-labeled water ([O-15]H2O) and positron emission tomography (PET), before and during (50 min) the bradykinin infusion, Glucose uptake was measured immediately after the blood flow measurement simultaneously in both femoral regions using [F-18]-fluoro-deoxy-glucose ([F-15]FDG) and PET, During hyperinsulinemia, muscle blood flow was 58% higher in the bradykinin-infused (38+/-9 ml/kg muscle . min) than in the control leg (24+/-5, P < 0.01), Femoral muscle glucose uptake was identical in both legs (60.6+/-9.5 vs. 58.7+/-9.0 mu mol/kg . min, bradykinin-infused vs, control leg, NS). Glucose extraction by skeletal muscle was 44% higher in the control (2.6+/-0.2 mmol/liter) than the bradykinin-infused leg (1.8+/-0.2 mmol/liter, P < 0.01), When bradykinin was infused in the basal state, flow was 98% higher in the bradykinin-infused (58+/-12 ml/kg muscle . min) than the control leg (28+/-6 ml/kg muscle . min, P < 0.01) but rates of muscle glucose uptake were identical in both legs (10.1+/-0.9 vs, 10.6+/-0.8 mu mol/kg . min), We conclude that bradykinin increases skeletal muscle blood flow but not muscle glucose uptake in vivo, These data provide direct evidence against the hypothesis that blood flow is an independent regulator of insulin-stimulated glucose uptake in humans.
引用
收藏
页码:1741 / 1747
页数:7
相关论文
共 69 条
[1]   HYPERINSULINEMIA PRODUCES BOTH SYMPATHETIC NEURAL ACTIVATION AND VASODILATION IN NORMAL HUMANS [J].
ANDERSON, EA ;
HOFFMAN, RP ;
BALON, TW ;
SINKEY, CA ;
MARK, AL .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (06) :2246-2252
[2]  
[Anonymous], 1960, METHODS MED RES
[3]   INTERACTIONS BETWEEN INSULIN AND NOREPINEPHRINE ON BLOOD-PRESSURE AND INSULIN SENSITIVITY - STUDIES IN LEAN AND OBESE MEN [J].
BARON, AD ;
BRECHTEL, G ;
JOHNSON, A ;
FINEBERG, N ;
HENRY, DP ;
STEINBERG, HO .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (06) :2453-2462
[4]   SKELETAL-MUSCLE BLOOD-FLOW - A POSSIBLE LINK BETWEEN INSULIN RESISTANCE AND BLOOD-PRESSURE [J].
BARON, AD ;
BRECHTELHOOK, G ;
JOHNSON, A ;
HARDIN, D .
HYPERTENSION, 1993, 21 (02) :129-135
[5]   MECHANISM OF INSULIN RESISTANCE IN INSULIN-DEPENDENT DIABETES-MELLITUS - A MAJOR ROLE FOR REDUCED SKELETAL-MUSCLE BLOOD-FLOW [J].
BARON, AD ;
LAAKSO, M ;
BRECHTEL, G ;
EDELMAN, SV .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1991, 73 (03) :637-643
[6]   HEMODYNAMIC ACTIONS OF INSULIN [J].
BARON, AD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (02) :E187-E202
[7]  
BARONAD, 1995, J CLIN INVEST, V96, P786
[8]   MYOSIN HEAVY-CHAIN COMPOSITION OF SINGLE FIBERS FROM NORMAL HUMAN-MUSCLE [J].
BIRAL, D ;
BETTO, R ;
DANIELIBETTO, D ;
SALVIATI, G .
BIOCHEMICAL JOURNAL, 1988, 250 (01) :307-308
[9]  
BONADONNA RC, 1993, DIABETES, V42, P181
[10]   ANGIOTENSIN-II INCREASES GLUCOSE-UTILIZATION DURING ACUTE HYPERINSULINEMIA VIA A HEMODYNAMIC MECHANISM [J].
BUCHANAN, TA ;
THAWANI, H ;
KADES, W ;
MODRALL, JG ;
WEAVER, FA ;
LAUREL, C ;
POPPITI, R ;
XIANG, A ;
HSUEH, W .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (02) :720-726