Cytochrome c Oxidase Activity as a Metabolic Regulator in Pancreatic Beta-Cells.
Cytochrome c Oxidase Activity as a Metabolic Regulator in Pancreatic Beta-Cells.
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DOI：
10.3390/cells11060929
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发表时间：
2022-03-08
期刊：
影响因子：
6
通讯作者：
Weksler-Zangen S
中科院分区：
文献类型：
--
作者：
Aharon-Hananel G;Romero-Afrima L;Saada A;Mantzur C;Raz I;Weksler-Zangen S
胰腺β细胞通过细胞色素c氧化酶（COX）（一种线粒体呼吸链酶）将葡萄糖刺激胰岛素分泌（GSIS）与氧化磷酸化结合起来。科恩糖尿病敏感（CDs）大鼠在喂食致糖尿病饮食时表现出高血糖，但在常规饮食中保持正常血糖。我们之前报道过cd大鼠COX活性降低，并探讨了其与2型糖尿病（T2D）的相关性。在这项研究中，我们研究了在糖尿病大鼠饲养4、11、20和30天的糖尿病发展过程中，以及在高血糖大鼠饲养7、11和20天的血糖恢复正常过程中，胰岛、外周血单核细胞（PBMCs）和GSIS的COX活性之间的关系。在饮食的不同时期进行口服葡萄糖耐量试验，测量血糖和胰岛素浓度。测定各组大鼠胰岛和外周血单核细胞在不同时期的COX活性。我们发现，cd -胰岛COX活性的逐渐降低与GSIS的降低呈正相关（R2 = 0.9691, p < 0.001），与血糖水平的升高呈负相关（R2 = 0.8396, p < 0.001）。当胰岛COX活性低于46%时，高血糖开始发生。逆转饮食恢复了46%的胰岛COX活性和GSIS，同时重建了正常血糖。有趣的是，PBMCs中COX活性与胰岛COX活性显著相关（R2 = 0.8944, p < 0.001）。我们的数据支持胰岛COX活性作为β细胞功能的主要代谢调节因子。pbmc和胰岛中COX活性的相关性可作为监测糖尿病β细胞功能障碍的无创生物标志物。
Pancreatic β-cells couple glucose-stimulated insulin secretion (GSIS) with oxidative phosphorylation via cytochrome c oxidase (COX), a mitochondrial respiratory-chain enzyme. The Cohen diabetic-sensitive (CDs) rats exhibit hyperglycemia when fed a diabetogenic diet but maintain normoglycemia on a regular diet. We have previously reported a decreased COX activity in CDs rats and explored its relevance for type 2 diabetes (T2D). In this study, we investigated the relation between COX activity in islets, peripheral-blood mononuclear cells (PBMCs), and GSIS during diabetes development in CDs rats fed a diabetogenic diet for 4, 11, 20, and 30 days and during reversion to normoglycemia in hyperglycemic CDs rats fed a reversion diet for 7, 11, and 20 days. An oral glucose-tolerance test was performed at different periods of the diets measuring blood glucose and insulin concentrations. COX activity was determined in islets and PBMCs isolated from rats at the different periods of the diets. We demonstrated a progressive reduction in COX activity in CDs-islets that correlated positively with the decreasing GSIS (R2 = 0.9691, p < 0.001) and inversely with the elevation in blood glucose levels (R2 = 0.8396, p < 0.001). Hyperglycemia was initiated when islet COX activity decreased below 46%. The reversion diet restored >46% of the islet COX activity and GSIS while re-establishing normoglycemia. Interestingly, COX activity in PBMCs correlated significantly with islet COX activity (R2 = 0.8944, p < 0.001). Our data support islet COX activity as a major metabolic regulator of β-cells function. The correlation between COX activity in PBMCs and islets may serve as a noninvasive biomarker to monitor β-cell dysfunction in diabetes.
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影响因子：
5.6
作者：
Dabravolski SA;Orekhova VA;Baig MS;Bezsonov EE;Starodubova AV;Popkova TV;Orekhov AN
通讯作者：
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影响因子：
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作者：
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