Insulin is required for prandial ghrelin suppression in humans
Insulin is required for prandial ghrelin suppression in humans
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DOI：
10.2337/diabetes.52.12.2923
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发表时间：
2003-12-01
期刊：
影响因子：
7.7
通讯作者：
De Feo, P
中科院分区：
文献类型：
--
作者：
Murdolo, G;Lucidi, P;De Feo, P
越来越多的证据表明ghrelin在调节食物摄入和能量稳态中起作用。在正常受试者中，循环ghrelin浓度在餐后摄入后降低，并在餐前逐渐增加。目前尚不清楚营养素是否通过刺激胰岛素分泌直接或间接抑制血浆ghrelin浓度。为了验证胰岛素调节人类餐后血浆ghrelin浓度的假设，我们比较了6名C肽阴性的1型糖尿病患者和6名年龄、性别和BMI匹配的健康受试者进餐对血浆ghrelin水平的影响。研究糖尿病受试者在不使用胰岛素（胰岛素戒断研究）、静脉输注基础胰岛素（基础胰岛素研究）和皮下给予餐时胰岛素剂量（餐时胰岛素研究）的情况下。膳食摄入抑制血浆ghrelin浓度在餐时胰岛素研究期间，正常对照组受试者中（105分钟时最低）降低32 +/- 4%，糖尿病患者中降低57 +/- 3%（与对照受试者相比P < 0.002），基础胰岛素研究期间为38 +/- 8%（P = 0.0016 vs.高胰岛素血症; P = NS vs.对照受试者），但在胰岛素戒断研究中没有任何影响（P < 0.001 vs.其他研究）。总之，1）胰岛素对于餐后诱导的血浆生长素释放肽抑制是必不可少的，2）基础胰岛素可用性足以抑制1型糖尿病受试者的餐后生长素释放肽，3）严重胰岛素缺乏引起的餐后诱导的生长素释放肽抑制的缺乏可以解释不受控制的1型糖尿病受试者的摄食过多。
Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis. In normal subjects, circulating ghrelin concentrations decrease after meal ingestion and increase progressively before meals. At present, it is not clear whether nutrients suppress the plasma ghrelin concentration directly or indirectly by stimulating insulin secretion. To test the hypothesis that insulin regulates postprandial plasma ghrelin concentrations in humans, we compared the effects of meal ingestion on plasma ghrelin levels in six C-peptide-negative subjects with type 1 diabetes and in six healthy subjects matched for age, sex, and BMI. Diabetic subjects were studied during absence of insulin (insulin withdrawal study), with intravenous infusion of basal insulin (basal insulin study) and subcutaneous administration of a prandial insulin dose (prandial insulin study). Meal intake suppressed plasma ghrelin concentrations (nadir at 105 min) by 32 +/- 4% in normal control subjects, 57 +/- 3% in diabetic patients during the prandial insulin study (P < 0.002 vs. control subjects), and 38 +/- 8% during basal insulin study (P = 0.0016 vs. hyperinsulinemia; P = NS vs. control subjects) but did not have any effect in the insulin withdrawal study (P < 0.001 vs. other studies). In conclusion, 1) insulin is essential for meal-induced plasma ghrelin suppression, 2) basal insulin availability is sufficient for postprandial ghrelin suppression in type 1 diabetic subjects, and 3) lack of meal-induced ghrelin suppression caused by severe insulin deficiency may explain hyperphagia of uncontrolled type 1 diabetic subjects.