Boden G, Chen X, Capulong E, Mozzoli M
Division of Endocrinology, Diabetes, and Metabolism, and the General Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Diabetes. 2001 Apr;50(4):810-6. doi: 10.2337/diabetes.50.4.810.
Effects of endogenously derived free fatty acids (FFAs) on rates of gluconeogenesis (GNG) (determined with 2H2O), 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 (from 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 micromol/l in type 2 diabetic patients and from 462 to 573 micromol/l in control subjects (P < 0.04), but GNG did not change in diabetic patients (6.9 vs. 6.5 micromol x kg(-1) x min(-1), P > 0.05) or in control subjects (5.1 vs. 5.4 micromol x kg(-1) x 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 micromol/l, respectively); GNG decreased (from 6.1 to 4.2 and from 4.7 to 3.5 micromol x kg(-1) x min(-1)), whereas GL decreased in diabetic patients (from 5.3 to 4.4 micromol x kg(-1) x min(-1)) but increased in control subjects (from 5.4 to 7.2 micromol x 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 micromol/l, respectively); GNG increased (from 4.2 to 5.4 and from 3.4 to 5.3 micromol x kg(-1) x min(-1) respectively), and GL decreased (from 4.4 to 3.4 and from 7.3 to 4.3 micromol x kg(-1) x min(-1), 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.
在18名2型糖尿病患者和7名非糖尿病对照受试者中，研究了内源性游离脂肪酸（FFA）对糖异生（GNG）速率（用2H2O测定）、糖原分解（GL）和内源性葡萄糖生成（EGP）的影响，实验条件有三种：1）在8小时禁食期间（最后一餐16 - 24小时后），此时血浆FFA水平缓慢上升；2）在给予烟酸（NA）4小时期间（禁食加NA，即16 - 20小时），此时血浆FFA急剧下降；3）在停用NA后4小时期间（FFA反弹，即20 - 24小时），此时血浆FFA急剧上升。禁食期间，2型糖尿病患者的FFA从636微摩尔/升升至711微摩尔/升，对照受试者从462微摩尔/升升至573微摩尔/升（P < 0.04），但糖尿病患者的GNG无变化（6.9对6.5微摩尔·千克-1·分钟-1，P > 0.05），对照受试者也无变化（5.1对5.4微摩尔·千克-1·分钟-1，P > 0.05）。禁食加NA期间，糖尿病患者和对照受试者的FFA均下降（分别从593降至193微摩尔/升和从460降至162微摩尔/升）；GNG下降（分别从6.1降至4.2微摩尔·千克-1·分钟-1和从4.7降至3.5微摩尔·千克-1·分钟-1），而糖尿病患者的GL下降（从5.3降至4.4微摩尔·千克-1·分钟-1），对照受试者的GL上升（从5.4升至7.2微摩尔·千克-1·分钟-1）。在FFA反弹期间，糖尿病患者和对照受试者的FFA均上升（分别从193升至1239微摩尔/升和从162升至1491微摩尔/升）；GNG上升（分别从4.2升至5.4微摩尔·千克-1·分钟-1和从3.4升至5.3微摩尔·千克-1·分钟-1），GL下降（分别从4.4降至3.4微摩尔·千克-1·分钟-1和从7.3降至4.3微摩尔·千克-1·分钟-1）。总之，在延长的过夜禁食期间，血浆FFA水平上升刺激GNG，而FFA水平下降则抑制糖尿病患者和对照受试者的GNG；最后一餐20小时后，糖尿病患者和对照受试者中约三分之一的GNG依赖于FFA；糖尿病患者中，GL对GNG下降的反应导致的EGP自动调节受损。
