Decreased muscle capillary permeability surface area in type 2 diabetic subjects
Decreased muscle capillary permeability surface area in type 2 diabetic subjects
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DOI：
10.1210/jc.2004-0947
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Lönnroth, P
中科院分区：
文献类型：
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作者：
Gudbjörnsdóttir, S;Sjöstrand, M;Lönnroth, P
在胰岛素抵抗状态下，由胰岛素诱导的肌肉毛细血管募集被认为是受损的。为了阐明2型糖尿病对胰岛素和葡萄糖的毛细血管转运的调控机制，我们直接计算了肌肉中葡萄糖和胰岛素的渗透性表面积乘积(PS)。在正常血糖-高胰岛素钳夹期间，对2型糖尿病男性受试者和年龄和体重匹配的对照组进行了肌肉内微透析结合前臂模型和血流测量。在稳态高胰岛素血症中，肥胖组和2型糖尿病受试者的动脉血糖分别为5.8+/-0.1和5.9+/-0.1 mmol/L[无显著意义(NS)]。肥胖组的静脉血糖显著低于2型糖尿病组，分别为4.3+/-02和4.9+/-0.2 mmol/L(P<；0.05)。肥胖组和2型糖尿病组的动脉胰岛素分别为1494+/-90和1458+/-132pmol/L(NS)，稳态高胰岛素血症时的葡萄糖输注率分别为10.8+/-0.8和7.2+/-0.4 mg/kg中心点分(P<；0.01)。在稳态高胰岛素血症期间，肥胖者的血糖PS显著高于对照组(1.1+/-0.2比0.5+/-0.1ml/min·100g，P<；0.05)。肥胖受试者的葡萄糖摄取量也显著高于对照组(3.0+/-0.4比1.8+/-0.3µmol/min中心点100g，P<；0.05)。在稳态高胰岛素血症时，肥胖组和糖尿病组的PS分别为0.4+/-0.1和0.3+/-0.1ml/min·100g，胰岛素摄取量分别为258+/-54和168+/-24。当两组受试者被合并在一起时，发现在稳态高胰岛素血症时，PS中的葡萄糖和葡萄糖摄取之间存在显著的相关性。肥胖组和糖尿病组稳态高胰岛素血症时骨骼肌血流量分别为1.9+/-0.2和2.3+/-0.4ml/100g.min(NS)。目前的数据清楚地表明，在胰岛素抵抗的2型糖尿病受试者的稳态高胰岛素血症期间，血糖的PS低于正常。此外，葡萄糖摄取与PS密切相关，而血流与PS无关。我们认为PS是高胰岛素血症时比肢体血流更敏感的胰岛素抵抗标志物。在2型糖尿病患者中发现的较低的毛细血管通过能力被认为是进一步加重胰岛素抵抗的原因。
Capillary recruitment in muscles, induced by insulin, has been proposed to be impaired in insulin-resistant states. To elucidate the mechanisms regulating capillary transport of insulin and glucose in type 2 diabetes, we directly calculated the permeability-surface area product (PS) for glucose and insulin in muscle.Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in type 2 diabetic male subjects and age- and weight-matched controls during a euglycemic-hyperinsulinemic clamp.During steady-state hyperinsulinemia, arterial plasma glucose was 5.8 +/- 0.1 and 5.9 +/- 0.1 mmol/liter [not significant (NS)] in the obese and type 2 diabetic subjects, respectively. Venous glucose was significantly lower in the obese group compared with the type 2 diabetic subjects, 4.3 +/- 02 vs. 4.9 +/- 0.2 mmol/liter (P < 0.05). Arterial insulin was 1494 +/- 90 and 1458 +/- 132 pmol/liter (NS) in the obese and type 2 diabetic subjects, respectively.The glucose infusion rate during steady-state hyperinsulinemia was 10.8 +/- 0.8 and 7.2 +/- 0.4 mg/kg center dot min in the obese and diabetic subjects, respectively (P < 0.01). Interstitial-arterial lactate difference was significantly higher in the obese subjects.During steady-state hyperinsulinemia, PS for glucose was significantly higher in the obese subjects (1.1 +/- 0.2 vs. 0.5 +/- 0.1 ml/min.100 g, P < 0.05). Glucose uptake was also significantly higher in the obese subjects (3.0 +/- 0.4 vs. 1.8 +/- 0.3 mu mol/min center dot 100 g, P < 0.05). During steady-state hyperinsulinemia, PS for insulin was 0.4 +/- 0.1 and 0.3 +/- 0.1 ml/min.100 g in the obese and diabetic subjects, respectively (NS), and insulin uptake was 258 +/- 54 vs. 168 +/- 24, respectively (NS). When both subject groups were pooled together, a significant correlation was found between PS for glucose and glucose uptake during steady-state hyperinsulinemia. Skeletal muscle blood flow during steady-state hyperinsulinemia was 1.9 +/- 0.2 and 2.3 +/- 0.4 ml/100 g.min in the obese and diabetic subjects, respectively (NS). Blood flow did not increase during hyperinsulinemia in either of the two groups.The present data clearly show that PS for glucose is subnormal during steady-state hyperinsulinemia in insulin-resistant type 2 diabetic subjects. Furthermore, there was a close correlation between glucose uptake and PS for glucose but not between blood flow and PS. We suggest that PS is a more sensitive marker for insulin resistance during hyperinsulinemia than limb flow. The lower capacity for transcapillary passage found in the type 2 diabetic subjects is suggested to further aggravate insulin resistance.