CHARACTERIZATION OF CELLULAR DEFECTS OF INSULIN ACTION IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS
CHARACTERIZATION OF CELLULAR DEFECTS OF INSULIN ACTION IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS
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DOI：
10.1172/jci116226
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发表时间：
1993-02-01
影响因子：
15.9
通讯作者：
DEFRONZO, RA
中科院分区：
文献类型：
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作者：
DELPRATO, S;BONADONNA, RC;DEFRONZO, RA
7名非胰岛素依赖型糖尿病（NIDDM）患者参加了3项钳夹试验，分别使用[3-H-3]和[U-C-14]葡萄糖和间接量热法：研究I，正常血糖（5.2+/-0.1 mM）胰岛素（269+/-39 pM）钳夹;研究II，高血糖（14.9+/-1.2 mM）胰岛素（259+/-19 pM）钳夹;研究III，正常血糖（5.5+/-0.3 mM）高胰岛素血症（1650+/-529 pM）钳夹。7名对照受试者接受正常血糖（5.1+/-0.2 mM）胰岛素（258+/-24 pM）钳夹。糖酵解和葡萄糖氧化从（H2O）-H-3和（CO2）-C-14的出现率进行定量;糖原合成计算为身体葡萄糖处置和糖酵解之间的差异。在研究I中，与对照组相比，NIDDM患者的葡萄糖摄取减少了54%。NIDDM患者糖酵解、糖原合成和葡萄糖氧化减少（P < 0.05-0.001）。非氧化性糖酵解和脂质氧化较高。在研究II和III中，NIDDM的葡萄糖摄取与对照组相同（40.7+/-2.1和40.7+/-1.7 mumol/min）。kg去脂质量）。在研究II中，糖酵解，而不是葡萄糖氧化，是正常的（P < 0.01与对照组）。非氧化糖酵解仍高于对照组（P < 0.05）。糖原沉积增加（与研究I相比P < 0.05），脂质氧化保持较高水平（P < 0.01）。在研究III中，高胰岛素血症使糖原形成、糖酵解和脂质氧化正常化，但未使非氧化糖酵解升高或葡萄糖氧化降低正常化。脂质氧化与糖酵解呈负相关（r = -0.65; P < 0.01），葡萄糖氧化呈负相关（r = -0.75; P < 0.01）。总之，在NIDDM：（a）胰岛素抵抗涉及糖酵解、糖原合成和葡萄糖氧化;（B）高血糖症和高胰岛素血症可使全身葡萄糖摄取正常化;（c）显著的高胰岛素血症使糖原合成和通过糖酵解的总流量正常化，但不能恢复氧化和非氧化糖酵解之间的正常分布;（d）高血糖症不能克服葡萄糖氧化和非氧化糖酵解中的缺陷;（e）脂质氧化升高，并且仅在高胰岛素血症时受到抑制。
Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-H-3]and [U-C-14]glucose and indirect calorimetry: study I, euglycemic (5.2+/-0.1 mM) insulin (269+/-39 pM) clamp; study II, hyperglycemic (14.9+/-1.2 mM) insulin (259+/-19 pM) clamp; study III, euglycemic (5.5+/-0.3 mM) hyperinsulinemic (1650+/-529 pM) clamp. Seven control subjects received a euglycemic (5.1+/-0.2 mM) insulin (258+/-24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of (H2O)-H-3 and (CO2)-C-14; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7+/-2.1 and 40.7+/-1.7 mumol/min . kg fat-free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia.