Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.
Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.
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氯卡色林抑制小鼠胰岛中葡萄糖刺激的胰岛素分泌和钙流入
DOI：
10.3389/fphar.2021.761966
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Jing M;Wang S;Li D;Wang Z;Li Z;Lu Y;Sun T;Qiu C;Chen F;Yu H;Zhang W
Lorcasein是一种针对5-羟色胺2C受体（5-HT2CR）的血清素能激动剂，FDA被批准用于长期管理肥胖症，或者没有至少一个与重量相关的合并症，可以限制胰岛素的敏感性和超级胰岛素。一种5-HT2CR激动剂，减少血浆在我们的实验室中，胰岛素的浓度和先前的研究发现，通过激活5-HT2CR对β细胞的胰岛素分泌（GSIS），lorcasein对胰腺的GSIS对胰腺的影响尚未在目前的β细胞中表达了5-HT2 CR Lorcasein抑制了5-HT2CR的ENT激活GSIS和SB242084或5-HT2CR的敲低在体外取消了Lorcasein的效果，洛杉矶也抑制了高脂饮食中的GSI（HFD）剂量的剂量依赖性的小鼠，但也没有改变胰岛素合成的含量。它是胰岛素分泌和（Ca2+）在Min6中的I氯化钾。 Ogue DB-cAMP与PTX相同。 PTX敏感的GαI/O蛋白在β细胞中降低了细胞内cAMP水平和Ca2+影响，从而导致β细胞的GSIS功能障碍突出显示了Lorcasein的新信号传导机制，并为5-HT2CR在β-Cell Biogy和IT的进一步研究提供了claseical and Cluendical and Cluner and clase inor in lor and cance in clundical and in clastical and clastical and clastical and clastical and clase and clase and cancin and cap的影响。
Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HT2CR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients’ appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HT2CR in the hypothalamus. It is known that the mCPP, a kind of 5-HT2CR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HT2CR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HT2CR was expressed in both mouse pancreatic β cells and β-cell–derived MIN6 cells. Dose-dependent activation of 5-HT2CR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HT2CR abolished lorcaserin’s effect in vitro. Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca2+)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca2+)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca2+ influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HT2CR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin.
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影响因子：
2.6
作者：
Higgins, Guy A;Desnoyer, Jill;Van Niekerk, Annalise;Silenieks, Leo B;Lau, Winnie;Thevarkunnel, Sandy;Izhakova, Julia;DeLannoy, Ines Am;Fletcher, Paul J;DeLay, Josepha;Dobson, Howard
通讯作者：
Dobson, Howard
影响因子：
8.1
作者：
Burke LK;Ogunnowo-Bada E;Georgescu T;Cristiano C;de Morentin PBM;Valencia Torres L;D'Agostino G;Riches C;Heeley N;Ruan Y;Rubinstein M;Low MJ;Myers MG;Rochford JJ;Evans ML;Heisler LK
通讯作者：
Heisler LK
影响因子：
4.7
作者：
Clemett, DA;Punhani, T;Fone, KCF
通讯作者：
Fone, KCF
影响因子：
4.8
作者：
Henquin, Jean-Claude;Nenquin, Myriam
通讯作者：
Nenquin, Myriam
影响因子：
5.8
作者：
Apovian, C.;Palmer, K.;Rubino, D.
通讯作者：
Rubino, D.