Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (UMC), Location AMC, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands.
Laboratory of Endocrinology, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam, the Netherlands.
Diabetologia. 2019 Nov;62(11):2088-2093. doi: 10.1007/s00125-019-4953-7. Epub 2019 Jul 20.
AIMS/HYPOTHESIS: The central pacemaker of the mammalian biological timing system is located within the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. Together with the peripheral clocks, this central brain clock ensures a timely, up-to-date and proper behaviour for an individual throughout the day-night cycle. A mismatch between the central and peripheral clocks results in a disturbance of daily rhythms in physiology and behaviour. It is known that the number of rhythmically expressed genes is reduced in peripheral tissue of individuals with type 2 diabetes mellitus. However, it is not known whether the central SCN clock is also affected in the pathogenesis of type 2 diabetes. In the current study, we compared the profiles of the SCN neurons and glial cells between type 2 diabetic and control individuals.
We collected post-mortem hypothalamic tissues from 28 type 2 diabetic individuals and 12 non-diabetic control individuals. We performed immunohistochemical analysis for three SCN neuropeptides, arginine vasopressin (AVP), vasoactive intestinal polypeptide (VIP) and neurotensin (NT), and for two proteins expressed in glial cells, ionised calcium-binding adapter molecule 1 (IBA1, a marker of microglia) and glial fibrillary acidic protein (GFAP, a marker of astroglial cells).
The numbers of AVP immunoreactive (AVP-ir) and VIP-ir neurons and GFAP-ir astroglial cells in the SCN of type 2 diabetic individuals were significantly decreased compared with the numbers in the SCN of the control individuals. In addition, the relative intensity of AVP immunoreactivity was reduced in the individuals with type 2 diabetes. The number of NT-ir neurons and IBA1-ir microglial cells in the SCN was similar in the two groups.
CONCLUSIONS/INTERPRETATION: Our data show that type 2 diabetes differentially affects the numbers of AVP- and VIP-expressing neurons and GFAP-ir astroglial cells in the SCN, each of which could affect the daily rhythmicity of the SCN biological clock machinery. Therefore, for effectively treating type 2 diabetes, lifestyle changes and/or medication to normalise central biological clock functioning might be helpful.
目的/假设：哺乳动物生物计时系统的中央起搏器位于下丘脑前部的视交叉上核（SCN）内。这个中央脑钟与外周时钟一起，确保个体在昼夜周期中始终保持及时、最新和适当的行为。中央时钟和外周时钟之间的不匹配会导致生理和行为的日常节律紊乱。已知 2 型糖尿病患者外周组织中节律表达基因的数量减少。然而，目前尚不清楚 2 型糖尿病的发病机制是否也会影响中央 SCN 时钟。在当前的研究中，我们比较了 2 型糖尿病患者和对照组个体的 SCN 神经元和神经胶质细胞的特征。
我们从 28 名 2 型糖尿病患者和 12 名非糖尿病对照组个体中收集死后下丘脑组织。我们对三种 SCN 神经肽（精氨酸加压素（AVP）、血管活性肠肽（VIP）和神经降压素（NT））和两种表达在神经胶质细胞中的蛋白质（离子钙结合衔接蛋白 1（IBA1，小胶质细胞的标志物）和神经胶质纤维酸性蛋白（GFAP，星形胶质细胞的标志物）进行免疫组织化学分析。
与对照组相比，2 型糖尿病患者 SCN 中的 AVP 免疫反应性（AVP-ir）和 VIP-ir 神经元和 GFAP-ir 星形胶质细胞数量明显减少。此外，2 型糖尿病患者的 AVP 免疫反应性相对强度降低。SCN 中 NT-ir 神经元和 IBA1-ir 小胶质细胞的数量在两组之间相似。
结论/解释：我们的数据表明，2 型糖尿病对 SCN 中 AVP 和 VIP 表达神经元和 GFAP-ir 星形胶质细胞的数量有不同的影响，这可能会影响 SCN 生物钟机制的日常节律性。因此，为了有效治疗 2 型糖尿病，改变生活方式和/或药物治疗以使其中央生物钟功能正常化可能会有所帮助。
