Mandarino L J, Madar Z, Kolterman O G, Bell J M, Olefsky J M
Am J Physiol. 1986 Oct;251(4 Pt 1):E489-96. doi: 10.1152/ajpendo.1986.251.4.E489.
To determine whether 1) insulin stimulates pyruvate dehydrogenase (PDH) and glycogen synthase (GS) in isolated human adipocytes and 2) adipocytes from subjects with obesity or noninsulin-dependent diabetes mellitus (NIDDM) are resistant to the effects of insulin, PDH and GS were assayed in adipocytes from 11 control, 8 obese, and 9 NIDDM subjects. Basal PDH activities were 123 +/- 20, 129 +/- 21, and 128 +/- 25 pmol pyruvate oxidized/min per 2 X 10(5) adipocytes in these groups. Insulin stimulated PDH activity to a maximum of 223 +/- 38 pmol/min per 2 X 10(5) in adipocytes from control subjects, but did not significantly increase values from obese subjects. Insulin significantly decreased PDH activity in cells from NIDDM subjects (99 +/- 20 pmol/min per 2 X 10(5) cells, P less than 0.05). PDH activity assayed with high magnesium and calcium concentrations was significantly stimulated by insulin in adipocytes from control, but not obese or NIDDM subjects. GS assayed with 1 mM glucose 6-phosphate did not differ significantly among control, obese, or NIDDM subjects (446 +/- 110, 451 +/- 156, and 291 +/- 35 pmol incorporated into glycogen, respectively). Insulin significantly stimulated glycogen synthase in all three groups (827 +/- 179, 764 +/- 177, and 569 +/- 51 pmol incorporated) to a similar extent. Glycogen synthase assayed with 10 mM glucose 6-phosphate was decreased in NIDDM (1,335 +/- 131 pmol incorporated) compared with obese or control subjects (2,512 +/- 451 and 2,239 +/- 230 pmol incorporated, respectively, P less than 0.01).
1)胰岛素是否能刺激分离出的人脂肪细胞中的丙酮酸脱氢酶(PDH)和糖原合酶(GS);2)肥胖或非胰岛素依赖型糖尿病(NIDDM)患者的脂肪细胞是否对胰岛素的作用产生抵抗,我们检测了11名对照者、8名肥胖者和9名NIDDM患者的脂肪细胞中的PDH和GS。这些组中,基础PDH活性分别为每2×10⁵个脂肪细胞每分钟氧化123±20、129±21和128±25 pmol丙酮酸。胰岛素可将对照者脂肪细胞中的PDH活性刺激至最高每2×10⁵个脂肪细胞每分钟223±38 pmol,但未显著提高肥胖者的值。胰岛素显著降低了NIDDM患者细胞中的PDH活性(每2×10⁵个细胞每分钟99±20 pmol,P<0.05)。在高镁和钙浓度下检测的PDH活性,胰岛素可显著刺激对照者的脂肪细胞,但对肥胖者或NIDDM患者的脂肪细胞无此作用。用1 mM葡萄糖6-磷酸检测的GS在对照者、肥胖者或NIDDM患者之间无显著差异(分别为446±110、451±156和291±35 pmol掺入糖原)。胰岛素在所有三组中均显著刺激糖原合酶(分别为827±179、764±177和569±51 pmol掺入),且程度相似。与肥胖者或对照者(分别为2512±451和2239±230 pmol掺入)相比,用10 mM葡萄糖6-磷酸检测的NIDDM患者的糖原合酶降低(1335±131 pmol掺入,P<0.01)。