Euglycemic hyperinsulinemia differentially modulates circulating total and acylated-ghrelin in humans
Euglycemic hyperinsulinemia differentially modulates circulating total and acylated-ghrelin in humans
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正常血糖的高胰岛素血症差异调节人体循环总生长素释放肽和酰化生长素释放肽
DOI：
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发表时间：
2008
影响因子：
5.4
通讯作者：
Andreas F. H. Pfeiffer
中科院分区：
文献类型：
--
作者：
M. Weickert;C. Loeffelholz;A. Arafat;Christof Schöfl;Bärbel Otto;Jochen Spranger;M. Möhlig;Andreas F. H. Pfeiffer
Ghrelin是一种强有力的促食欲的肠道激素。在急性和慢性高胰岛素血症状态下，总饥饿素的循环浓度都受到食物摄入的下调。然而，在血液中，去酰化（去酰基）生长素释放肽是在人类中没有食欲作用的主要形式。循环中的酰基-胃饥饿素已被证实在餐后和通过药理学高胰岛素血症被抑制。然而，到目前为止，还没有报道循环酰基-生长素释放肽对中度高胰岛素血症和高胰岛素血症-高胰岛素血症钳夹条件的反应。使用两步正常血糖-高胰岛素钳夹法（40 mU胰岛素/m2/min;平均148±7 min达到稳态，随后300 min脂质/肝素输注）研究了14例健康受试者。在整个夹具中以定时间隔测量总生长素释放肽和酰基-生长素释放肽的响应。通过减法计算去酰基-生长素释放肽浓度。与基线浓度相比，总生长素释放肽显著降低（819±92 vs 564±58 pg/ml，p<0.001），从而证实了先前的观察结果。去酰基生长素释放肽紧随总生长素释放肽浓度，并且相对于基线显著降低（772±92 vs 517±56 pg/ml，p<0.001）。相比之下，正常血糖-高胰岛素血症和正常血糖-高胰岛素血症-高脂血症都没有将整个钳夹过程中的酰基胃饥饿素浓度抑制在基线浓度以下（46±3 vs 47±8 pg/ml，p=0.90）。总之，中度高胰岛素血症和高胰岛素血症-高血脂钳夹条件差异调节人类循环总生长素和酰基生长素。胰岛素和脂质浓度变化以外的其他因素可能导致先前报告的餐后循环酰基-生长激素释放肽减少。
Ghrelin is a powerful orexigenic gut hormone. Circulating concentrations of total ghrelin are downregulated by food intake in both acute and chronic hyperinsulinemic states. However, in blood des-acylated (des-acyl) ghrelin is the predominant form that has no orexigenic effects in humans. Circulating acyl-ghrelin has been shown to be suppressed post-prandially and by pharmacological hyperinsulinemia. However, up to now responses of circulating acyl-ghrelin to moderate hyperinsulinemic and hyperinsulinemic-hyperlipidemic clamp conditions have not been reported. Fourteen healthy subjects were investigated using two-stepped euglycemic-hyperinsulinemic clamps (40 mU insulin/m2/min; mean 148±7 min till steady state, followed by 300 min lipid/heparin infusion). Responses of total ghrelin and acyl-ghrelin were measured at timed intervals throughout the clamps. Des-acyl-ghrelin concentrations were calculated by subtraction. Total ghrelin significantly decreased vs baseline concentrations (819±92 vs 564±58 pg/ml, p<0.001), thereby confirming previous observations. Des-acyl ghrelin closely followed total ghrelin concentrations and significantly decreased vs baseline (772±92 vs 517±56 pg/ml, p<0.001). In contrast, neither euglycemic-hyperinsulinemia nor euglycemic-hyperinsulinemic-hyperlipidemia suppressed acyl-ghrelin below baseline concentrations throughout the clamps (46±3 vs 47±8 pg/ml, p=0.90). In conclusion, moderate hyperinsulinemic and hyperinsulinemic-hyperlipidemic clamp conditions differentially modulated circulating total ghrelin and acylghrelin in humans. Factors other than changes in insulin and lipid concentrations are likely to contribute to the previously reported post-prandial reduction of circulating acyl-ghrelin.
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DOI：
10.1210/jcem.87.8.8879
发表时间：
2002-08
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
M. Saad;Basem Z Bernaba;C. Hwu;Sujata D Jinagouda;Salwa Fahmi;E. Kogosov;Rima Boyadjian
通讯作者：
M. Saad;Basem Z Bernaba;C. Hwu;Sujata D Jinagouda;Salwa Fahmi;E. Kogosov;Rima Boyadjian
影响因子：
15.9
作者：
FERRANNINI, E;BARRETT, EJ;DEFRONZO, RA
通讯作者：
DEFRONZO, RA
DOI：
10.1152/ajpendo.00569.2001
发表时间：
2003-02-01
影响因子：
5.1
作者：
Flanagan, DE;Evans, ML;Sherwin, RS
通讯作者：
Sherwin, RS
影响因子：
7.7
作者：
Cummings, DE;Purnell, JQ;Weigle, DS
通讯作者：
Weigle, DS