Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans
Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans
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DOI：
10.1152/ajpendo.00330.2007
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发表时间：
2007-11-01
影响因子：
5.1
通讯作者：
Anderwald, Christian
中科院分区：
文献类型：
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作者：
Anderwald-Stadler, Marietta;Krebs, Michael;Anderwald, Christian
Obestatin 是一种最近发现的 23 个氨基酸肽，以与生长素释放肽 (ghrelin) 拮抗的方式参与食欲和体重的调节，两者均源自共同的前体肽。生长素释放肽被证明与胰岛素抵抗有关，这也可能影响肥胖抑制素。我们研究了高（IS；n = 18，13 名女性和 5 名男性，年龄 47 +/- 2 岁，BMI = 25.5 +/- 0.9 kg/m(2)）和低（IR；n = 18，12 名女性和 6 名男性，年龄 45 +/- 2 岁，P = 0.49，BMI = 27.5 +/- 1.1 kg/m(2)，P = 0.17) 胰岛素刺激葡萄糖处理 (M)，通过 2 小时高胰岛素 (40 mU . min(-1) . m(-2)) 等血糖钳夹试验测量。 IS 组的 M100-120 分钟 (10.7 +/- 0.7) 高于 IR 组 (4.4 +/- 0.2 mg . min(-1) . kg(-1)，P < 10(-9))，而 IR 组血浆中游离脂肪酸 (FFA) 的胰岛素依赖性抑制降低（71 +/- 6% 对比 IS：82 +/- 5%，P < 0.02）。在两组中，空腹时的血浆生长素释放肽浓度相当，并且在胰岛素输注期间同样降低了 24-28%。 IR 具有较低的空腹血浆肥胖抑制素水平（383 +/- 26 pg/ml 对比 IS：469 +/- 23 pg/ml，P < 0.02）。在 IS 中，钳夹胰岛素输注可将血浆肥胖抑制素降低至与基础值相似的 81%（P < 0.00002），但在 IR 中则不然。空腹血浆肥胖抑制素与 M（r = 0.34，P = 0.04）、HDL 胆固醇（r = 0.45，P = 0.01）和血浆生长素释放肽浓度（r = 0.80，P < 0.000001）呈正相关，与肥胖测量、钳夹期间血浆 FFA 呈负相关（r =-0.42，P = 0.01），收缩压（r =-0.33，P < 0.05）。总之，在非糖尿病人群中，肥胖素（而非生长素释放肽）的空腹血浆浓度在胰岛素抵抗中降低，并且与全身胰岛素敏感性呈正相关。此外，在胰岛素敏感者中，血浆肥胖抑制素会被胰岛素降低，但在胰岛素抵抗者中则不会。
Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 +/- 2 yr, BMI = 25.5 +/- 0.9 kg/m(2)) and low (IR; n = 18, 12 females and 6 males, age 45 +/- 2 yr, P = 0.49, BMI = 27.5 +/- 1.1 kg/m(2), P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU . min(-1) . m(-2)) isoglycemic clamp tests. M100-120 min was higher in IS (10.7 +/- 0.7) than in IR (4.4 +/- 0.2 mg . min(-1) . kg(-1), P < 10(-9)), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 +/- 6% vs. IS: 82 +/- 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24-28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 +/- 26 pg/ml vs. IS: 469 +/- 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to similar to 81% of basal values in IS (P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M (r = 0.34, P = 0.04), HDL cholesterol (r = 0.45, P = 0.01), and plasma ghrelin concentrations (r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp (r =-0.42, P = 0.01), and systolic blood pressure (r =-0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.