Kullmann Stephanie, Fritsche Andreas, Wagner Robert, Schwab Sophia, Häring Hans-Ulrich, Preissl Hubert, Heni Martin
Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
Physiol Behav. 2017 Jul 1;176:134-138. doi: 10.1016/j.physbeh.2017.03.036. Epub 2017 Mar 24.
Activity of the hypothalamus - the major brain area controlling peripheral metabolism - is specifically modulated by insulin. Research in animals suggests that brain insulin action influences pancreatic insulin secretion.
We investigated the association between hypothalamic insulin sensitivity and pancreatic insulin secretion in humans.
This was a clinical-experimental trial in an university hospital setting.
48 healthy volunteers (21 women and 27 men) were included.
Insulin sensitivity of the hypothalamus was quantified by cerebral blood flow (CBF) using MRI in combination with intranasal insulin administration. On a different day, a 75g oral glucose tolerance test with glucose, insulin, and C-peptide levels measured at five time points was performed. Three established insulin secretion indices (insulinogenic index [IGI], corrected insulin response [CIR], and AUC/AUC) were then analyzed for correlations with hypothalamic insulin sensitivity independent of whole-body insulin sensitivity.
Hypothalamic insulin sensitivity showed a significant association with all three investigated insulin secretion indices (IGI p=0.0043; CIR p=0.06; AUC/AUC p=0.0179). Participants with a strong hypothalamic insulin effect (i.e. decreased CBF after intranasal insulin administration) had lower insulin secretion during the OGTT, whereas participants with hypothalamic insulin resistance had substantially higher insulin secretion. No correlations with the occipital cortex, a control region, were detected.
Our data suggest that hypothalamic insulin resistance might contribute to pancreatic insulin hypersecretion. Alternatively, common pathogenetic mechanisms could introduce both brain insulin resistance and beta cell hypersecretion.
下丘脑是控制外周代谢的主要脑区，其活动受到胰岛素的特异性调节。动物研究表明，脑胰岛素作用会影响胰腺胰岛素分泌。
我们研究了人类下丘脑胰岛素敏感性与胰腺胰岛素分泌之间的关联。
这是一项在大学医院环境中进行的临床实验性试验。
纳入了48名健康志愿者（21名女性和27名男性）。
通过磁共振成像（MRI）结合鼻内胰岛素给药，利用脑血流量（CBF）对下丘脑胰岛素敏感性进行量化。在另一天，进行了一次75克口服葡萄糖耐量试验，在五个时间点测量葡萄糖、胰岛素和C肽水平。然后分析了三个既定的胰岛素分泌指标（胰岛素生成指数[IGI]、校正胰岛素反应[CIR]和AUC/AUC）与下丘脑胰岛素敏感性之间的相关性，且独立于全身胰岛素敏感性。
下丘脑胰岛素敏感性与所有三个研究的胰岛素分泌指标均显示出显著关联（IGI p = 0.0043；CIR p = 0.06；AUC/AUC p = 0.0179）。下丘脑胰岛素作用较强的参与者（即鼻内胰岛素给药后CBF降低）在口服葡萄糖耐量试验期间胰岛素分泌较低，而下丘脑胰岛素抵抗的参与者胰岛素分泌则显著较高。未检测到与作为对照区域的枕叶皮质的相关性。
我们的数据表明，下丘脑胰岛素抵抗可能导致胰腺胰岛素分泌过多。或者，共同的致病机制可能导致脑胰岛素抵抗和β细胞分泌过多。
