基于“脾虚致消”理论探讨健脾清热法通过AMPK/mTORC1/SAD-A通路防治糖尿病机制研究设想
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摘要
胰岛β细胞功能异常是糖尿病的发病关键,AMPK/mTORC1/SAD-A信号通路参与调控胰岛β细胞的形态和功能。脾虚致消是糖尿病发病的主要病机,健脾清热法是糖尿病的主要治法,并通过调节信号通路改善胰岛β细胞功能。mTORC1位于信号中心双向调控AMPK和SAD-A的活性,mTORC1的枢纽作用与"脾"的功能密切相关,从AMPK/mTORC1/SAD-A信号通路角度探讨胰岛β细胞功能障碍,有助于深入探寻健脾清热法改善胰岛β细胞功能的作用机制,为中医药治疗糖尿病的机制研究提供新的研究方向。
Islet β-cell dysfunction is the key to the pathogenesis of diabetes, and AMPK/mTORC1/SAD-A signal pathway is involved in the regulation of islet β cell morphology and function. Spleen deficiency causing consumption is the main pathogenesis of diabetes. Invigorating the spleen and clearing heat method is the main diabetes treatment method by improving the signaling pathway to make the islet β cell function better. The activity of AMPK and SD-A is regulated by mTORC1 located in signal center. The pivotal role of mTORC1 is closely related to the function of the ‘spleen'. Discussing pancreatic β-cell dysfunction from the AMPK/mTORC1/SAD-A signaling pathway perspective is helpful to further explore the mechanism of invigorating the spleen and clearing heat method to improve the mechanism of pancreatic β-cells, and to provide a new research direction for the study of the mechanism of traditional Chinese medicine in treating diabetes mellitus.
Islet β-cell dysfunction is the key to the pathogenesis of diabetes, and AMPK/mTORC1/SAD-A signal pathway is involved in the regulation of islet β cell morphology and function. Spleen deficiency causing consumption is the main pathogenesis of diabetes. Invigorating the spleen and clearing heat method is the main diabetes treatment method by improving the signaling pathway to make the islet β cell function better. The activity of AMPK and SD-A is regulated by mTORC1 located in signal center. The pivotal role of mTORC1 is closely related to the function of the ‘spleen'. Discussing pancreatic β-cell dysfunction from the AMPK/mTORC1/SAD-A signaling pathway perspective is helpful to further explore the mechanism of invigorating the spleen and clearing heat method to improve the mechanism of pancreatic β-cells, and to provide a new research direction for the study of the mechanism of traditional Chinese medicine in treating diabetes mellitus.
引文
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[15]Nie J,Sun C,Faruque O,et al.Synapses of amphids defective(SAD-A)kinase promotes glucose-stimulated insulin secretion throughactivation of p21-activated kinase(PAK1)in pancreaticβ-Cells.Journal of Biological Chemistry,2012,287(31):26435-26444
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[22]李俊燕,陶枫,陈清光,等.健脾清化方对糖尿病大鼠血液基因表达谱的影响.中华中医药杂志,2015,30(11):4070-4073
[23]郭俊杰,潘云蓉,赵玉立.益气化浊胶囊通过AMPK信号通路改善胰岛素抵抗的实验研究.中华中医药学刊,2013,31(12):2685-2688
[24]Gleason C E,Lu D,Witters L A,et al.The role of AMPK and mTORin nutrient sensing in pancreatic beta-cells.Journal of Biological Chemistry,2007,282(14):10341-10351
[25]Swisa A,Granot Z,Tamarina N,et al.Loss of liver kinase B1(LKB1)in beta cells enhances glucose-stimulated insulin secretion despiteprofound mitochondrial defects.Journal of Biological Chemistry,2015,290(34):20934-209346
[26]Jia Nie,Xiao Han,Yuguang Shi.SAD-A and AMPK kinases:The ‘yinand yang’ regulators of mTORC1 signaling in pancreaticβcells.Cell Cycle,2013,12(21):3366-3369
[2]Wang L,Gao P,Zhang M,et al.Prevalence and Ethnic Patternof Diabetes and Prediabetes in China in 2013.JAMA,2017,317(24):2515-2523
[3]Mcewan P,Foos V,Lamotte M.Investigating The Impact ofContemporary Risk Factors for Diabetes Complications and TheirEvolution on Risk Prediction Using The Ukpds 82 Equations.Valuein Health,2015,18(7):A700
[4]Holman R R.Assessing the potential for alpha-glucosidaseinhibitors in prediabetic states.Diabetes Res Clin Pract,1998,40(Suppl 1):S21-25
[5]Bensellam M,Laybutt D R,Jonas J C.The molecular mechanismsof pancreaticβ-cell glucotoxicity:Recent findings and futureresearch directions.Molecular&Cellular Endocrinology,2012,364(1-2):1-27
[6]Krishan S,Richardson D R,Sahni S.Adenosine monophosphate-activated kinase and its key role in catabolism:Structure,regulation,biological activity,and pharmacological activation.Molecular Pharmacology,2015,87(3):363-377
[7]Li X,Wang L,Zhou X E,et al.Structural basis of AMPK regulation byadenine nucleotides and glycogen.Cell Research,2015,25(1):50-66
[8]Scott J W,Ling N,Issa S M,et al.Small molecule drug A-769662 andAMP synergistically activate naive AMPK independent of upstreamkinase signaling.Chemistry&Biology,2014, 21(5):619-627
[9]Jiang Y,Huang W,Wang J,et al.Metformin plays a dual role in MIN6pancreaticβcell function through AMPK-dependent autophagy.International Journal of Biological Sciences,2014,10(3):268-277
[10]Gleason C E,Lu D,Witters L A,et al.The role of AMPK and mTORin nutrient sensing in pancreatic beta-cells.Journal of Biological Chemistry,2007,282(14):10341-10351
[11]Mori H,Inoki K,Opland D,et al.Critical roles for the TSC-m TORpathway inβ-cell function.American Journal of PhysiologyEndocrinology&Metabolism,2009,297(5):E1013-E1022
[12]肖昊,谭碧娥,吴苗苗,等.信号通路调节细胞能量代谢的机制.中国科学:生命科学,2015,45(11):1124-1131
[13]Miao X Y,Gu Z Y,Liu P,et al.The human glucagon-like peptide-1analogue liraglutide regulates pancreatic beta-cell proliferation andapoptosis via an AMPKmTORP70S6K signaling pathway.Peptides,2013,39(1):71-79
[14]Nie J,Lilley B N,Pan Y A,et al.SAD-A kinase enhances insulinsecretion as a downstream target of GLP-1 signaling in pancreaticβ-cells.Molecular&Cellular Biology,2013, 33(13):2527-2534
[15]Nie J,Sun C,Faruque O,et al.Synapses of amphids defective(SAD-A)kinase promotes glucose-stimulated insulin secretion throughactivation of p21-activated kinase(PAK1)in pancreaticβ-Cells.Journal of Biological Chemistry,2012,287(31):26435-26444
[16]钱秋海,程益春.健脾降糖饮治疗糖尿病临床与实验研究.中医杂志,1991,30(11):29-31
[17]黄延芹.健脾消渴方对型糖尿病大鼠胰岛细胞分泌功能的影响.中医杂志,2015, 56(3):249-252
[18]孙丰雷,程益春,夏丽英,等.健脾降糖饮对四氧嘧啶糖尿病大鼠一氧化氮和内皮素的影响.中国实验方剂学杂志,2001,7(5):34-36
[19]孙丰雷,程益春,夏丽英,等.健脾降糖饮对四氧嘧啶糖尿病大鼠TNFα和GMP-140的影响.中国中医基础医学杂志,2002,8(8):23-24
[20]李丽,杨文军,尤晓珂.糖胰生号方治疗糖耐量减低患者的临床疗效观察.广州中医药大学学报,2017,34(1):13-16
[21]李俊燕,陶枫,陈清光,等.健脾清化方对型糖尿病大鼠基因表达谱及信号通路的影响.中医杂志,2015,56(17):1498-1501
[22]李俊燕,陶枫,陈清光,等.健脾清化方对糖尿病大鼠血液基因表达谱的影响.中华中医药杂志,2015,30(11):4070-4073
[23]郭俊杰,潘云蓉,赵玉立.益气化浊胶囊通过AMPK信号通路改善胰岛素抵抗的实验研究.中华中医药学刊,2013,31(12):2685-2688
[24]Gleason C E,Lu D,Witters L A,et al.The role of AMPK and mTORin nutrient sensing in pancreatic beta-cells.Journal of Biological Chemistry,2007,282(14):10341-10351
[25]Swisa A,Granot Z,Tamarina N,et al.Loss of liver kinase B1(LKB1)in beta cells enhances glucose-stimulated insulin secretion despiteprofound mitochondrial defects.Journal of Biological Chemistry,2015,290(34):20934-209346
[26]Jia Nie,Xiao Han,Yuguang Shi.SAD-A and AMPK kinases:The ‘yinand yang’ regulators of mTORC1 signaling in pancreaticβcells.Cell Cycle,2013,12(21):3366-3369