Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes
Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes
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DOI：
10.2337/diabetes.50.4.810
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发表时间：
2001-04-01
期刊：
影响因子：
7.7
通讯作者：
Mozzoli, M
中科院分区：
文献类型：
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作者：
Boden, G;Chen, XH;Mozzoli, M
在 18 名 2 型糖尿病患者和 7 名非糖尿病对照受试者中，在三种实验条件下研究了内源性游离脂肪酸 (FFA) 对糖异生 (GNG) 速率（用 (H2O)-H-2 测定）、糖原分解 (GL) 和内源性葡萄糖生成 (EGP) 的影响：1) 禁食 8 小时期间（最后一餐后 16-24 小时），当血浆 FFA水平缓慢上升； 2) 烟酸（NA）给药（空腹加NA）4小时（16-20小时）期间，血浆FFA急剧下降； 3) 停止 NA 后 4 小时（20-24 小时）期间（FFA 反弹），此时血浆 FFA 急剧增加。禁食期间，2型糖尿病患者的FFA从636μmol/l增加到711μmol/l，对照组从462μmol/l增加到573μmol/l（P < 0.04），但糖尿病患者（6.9 vs. 6.5 mol . kg(-1) . min(-1)，P > 0.05）或对照组（5.1 vs. 5.4 mu）GNG没有变化。摩尔 千克(-1) 分钟（-1），P > 0.05）。在禁食加 NA 期间，糖尿病患者和对照受试者的 FFA 下降（分别从 593 至 193 微摩尔/升和从 460 至 162 微摩尔/升）； GNG下降（从6.1下降到4.2，从4.7下降到3.5 mu mol . k(-1) . min(-1)），而GL在糖尿病患者中下降（从5.3下降到4.4 mu mol kg(-1) min(-1)），但在对照组中上升（从5.4上升到7.2 mu mol . kg(-1) min(-1)）。在FFA反弹期间，糖尿病患者和对照受试者的FFA增加（分别从193μmol/l增加到1,239μmol/l和从162μmol/l增加到1,491μmol/l）； GNG增加(分别从4.2到5.4和从3.4到5.3μmol·kg(-1)·min(-1))，GL降低(分别从4.4到3.4和从7.3到4.3μmol·kg-l·min-l)。总之，在糖尿病和对照受试者中，在延长的过夜禁食期间，血浆 FFA 水平的增加会刺激 GNG，而 FFA 水平的降低会抑制 GNG。最后一餐后 20 小时，糖尿病受试者和对照组受试者中大约三分之一的 GNG 依赖于 FFA；糖尿病患者中，GL 响应 GNG 减少而进行的 EGP 自动调节受到损害。
Effects of endogenously derived free fatty acids (FFAs) on rates of gluconeogenesis (GNG) (determined with (H2O)-H-2), glycogenolysis (GL), and endogenous glucose production (EGP) were studied in 18 type 2 diabetic patients and in 7 nondiabetic control subjects under three experimental conditions: 1) during an 8-h fast (hom 16-24 h after the last meal), when plasma FFA levels increased slowly; 2) during 4 h (from 16-20 h) of nicotinic acid (NA) administration (fasting plus NA), when plasma FFAs decreased acutely; and 3) during 4 h (from 20-24 h) after discontinuation of NA (FFA rebound), when plasma FFAs increased acutely. During fasting, FFAs increased from 636 to 711 mu mol/l in type 2 diabetic patients and from 462 to 573 mu mol/l in control subjects (P < 0.04), but GNG did not change in diabetic patients (6.9 vs. 6.5 mol . kg(-1) . min(-1), P > 0.05) or in control subjects (5.1 vs. 5.4 mu mol . kg(-1) min(-1), P > 0.05). During fasting plus NA, FFAs decreased in diabetic patients and control subjects (from 593 to 193 and from 460 to 162 mu mol/l, respectively); GNG decreased (from 6.1 to 4.2 and from 4.7 to 3.5 mu mol . k(-1) . min(-1)), whereas GL decreased in diabetic patients (from 5.3 to 4.4 mu mol kg(-1) min(-1)) but increased in control subjects (from 5.4 to 7.2 mu mol . kg(-1) min(-1)). During the FFA rebound, FFAs increased in diabetic patients and control subjects (from 193 to 1,239 and from 162 to 1,491 mu mol/l, respectively); GNG increased (from 4.2 to 5.4 and from 3.4 to 5.3 mu mol . kg(-1) . min(-1) respectively), and GL decreased (from 4.4 to 3.4 and from 7.3 to 4.3 mu mol kg-l min-l, respectively). In summary, during an extended overnight fast, increasing plasma FFA levels stimulated GNG, whereas decreasing FFA levels inhibited GNG in both diabetic and control subjects; 20 h after the last meal, approximately one-third of GNG in both diabetic and control subjects was dependent on FFAs; and autoregulation of EGP by GL in response to decreasing GNG was impaired in diabetic patients.