CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.
CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.
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DOI：
10.1016/j.celrep.2018.05.035
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发表时间：
2018-06-12
期刊：
影响因子：
8.8
通讯作者：
Knudsen JG
中科院分区：
文献类型：
--
作者：
Briant LJB;Dodd MS;Chibalina MV;Rorsman NJG;Johnson PRV;Carmeliet P;Rorsman P;Knudsen JG
胰升糖素是主要的高血糖激素，通常由胰岛α细胞分泌，作为对低血糖的反调节反应的一部分。因此，在低糖供应的条件下，α细胞的分泌输出是高需求的。许多组织氧化脂肪作为一种替代能量底物。在这里，我们证明了在低糖条件下，小鼠和人类胰岛中的胰高血糖素的分泌都是由脂肪酸代谢维持的，而抑制这一代谢途径通过去极化α细胞膜电位和降低动作电位幅度来显著减少胰高血糖素的输出。我们通过实验和计算方法证明，这不是由KATP通道介导的，而是由于Na+-K+泵的运行减少所致。这些数据表明，胰高血糖素的逆调节分泌是由脂肪酸代谢驱动的，Na+-K+泵是α细胞功能的重要依赖于三磷酸腺苷的调节因子。依赖CPT1a的FAO在小鼠和人的胰岛中失去了依赖CPT1a的FAO减少了胰高血糖素的分泌，CPT1a依赖的FAO通过向Na+-K+-ATPase供应三磷酸腺苷来维持胰高血糖素的分泌，CPT1a依赖的FAO有助于胰高血糖素的逆向调节分泌，高血糖素是在低血糖条件下从胰腺α细胞分泌的。Briant等人。证明这种反应是由脂肪酸氧化推动的。氧化产生的能量用于维持膜电位动态、动作电位形态和Na+-K+泵的活性。
Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet α cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from α cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing α cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the KATP channel, but instead due to reduced operation of the Na+-K+ pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na+-K+ pump is an important ATP-dependent regulator of α cell function. Glucagon secretion in low glucose is maintained by CPT1a-dependent FAO Loss of CPT1a-dependent FAO in mouse and human islets decreases glucagon secretion CPT1a-dependent FAO maintains glucagon secretion by supplying ATP to the Na+-K+-ATPase CPT1a-dependent FAO contributes to the counter-regulatory secretion of glucagon Glucagon is secreted from pancreatic α cells in hypoglycemic conditions. Briant et al. demonstrate that this response is fueled by fatty acid oxidation. The energy generated by oxidation is used to maintain membrane potential dynamics, action potential morphology, and Na+-K+ pump activity.
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影响因子：
3.4
作者：
Gylfe E
通讯作者：
Gylfe E
影响因子：
4.8
作者：
Diaz, Monica;Antonescu, Costin N.;Planas, Josep V.
通讯作者：
Planas, Josep V.
影响因子：
8.8
作者：
Adam J;Ramracheya R;Chibalina MV;Ternette N;Hamilton A;Tarasov AI;Zhang Q;Rebelato E;Rorsman NJG;Martín-Del-Río R;Lewis A;Özkan G;Do HW;Spégel P;Saitoh K;Kato K;Igarashi K;Kessler BM;Pugh CW;Tamarit-Rodriguez J;Mulder H;Clark A;Frizzell N;Soga T;Ashcroft FM;Silver A;Pollard PJ;Rorsman P
通讯作者：
Rorsman P
影响因子：
7.7
作者：
Allister EM;Robson-Doucette CA;Prentice KJ;Hardy AB;Sultan S;Gaisano HY;Kong D;Gilon P;Herrera PL;Lowell BB;Wheeler MB
通讯作者：
Wheeler MB
DOI：
10.1113/jp274581
发表时间：
2018-01-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Briant LJB;Reinbothe TM;Spiliotis I;Miranda C;Rodriguez B;Rorsman P
通讯作者：
Rorsman P