胰腺β细胞再生的研究进展
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摘要
糖尿病是一种慢性代谢病,其发生与β细胞密切相关,例如β细胞数量减少以及功能缺陷都会导致糖尿病,并且容易引起诸多并发症,所以治疗糖尿病的有效方法之一就是增加β细胞的数量或恢复其功能。论文对β细胞再生的研究进展进行了综述,包括β细胞再生的依据,体外和体内已分化的成体细胞的新生,非胰腺细胞的新生以及其他内分泌细胞的转化,旨在为临床上糖尿病的治疗提供参考。
Diabetes is a chronic metabolic disease whose occurrence is closely related to beta cells.For example,a decrease in the number of beta cells and functional defects both can lead to diabetes.And it can easily causes many complications.So an effective way to treat diabetes is to increase the number of beta cells or restore their function.This paper reviewed the progress on beta cell regeneration,including the basis for beta cell regeneration,in vitro and in vivo regeneration of differentiated somatic cells,non-pancreatic cell renewal and the transformation of other endocrine cells.The aim was to provide reference for the treatment of clinical diabetes.
Diabetes is a chronic metabolic disease whose occurrence is closely related to beta cells.For example,a decrease in the number of beta cells and functional defects both can lead to diabetes.And it can easily causes many complications.So an effective way to treat diabetes is to increase the number of beta cells or restore their function.This paper reviewed the progress on beta cell regeneration,including the basis for beta cell regeneration,in vitro and in vivo regeneration of differentiated somatic cells,non-pancreatic cell renewal and the transformation of other endocrine cells.The aim was to provide reference for the treatment of clinical diabetes.
引文
[1]刘静.2型糖尿病肾病的相关危险因素分析[J].保健文汇,2016(10):34.
[2]宋光艳.抗糖尿病药物的临床应用[J].中国保健营养,2016,26(22):206.
[3] Wang L,Gao P,Zhang M,et al.Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013[J].JAMA,2017,317(24):2515.
[4]王鹤霏.脂肪间充质干细胞治疗大鼠I型糖尿病的效果及机理探讨[D].内蒙古呼和浩特:内蒙古大学,2016.
[5] Aguayomazzucato C,Bonnerweir S.Pancreaticβcell regeneration as a possible therapy for diabetes.[J].Cell Metabolism,2017,27(1):57-67.
[6]张辰,赵振民,张翔宇,等.干细胞诱导分化为产胰岛素细胞的研究进展[J].现代生物医学进展,2016,16(7):1350-1353.
[7]朱剑,刘超.胰岛β细胞再生——糖尿病治疗的新思路[J].国际内分泌代谢杂志,2008,28(1):48-52.
[8] Stewart A F.Betatrophin versus bitter-trophin and the elephant in the room:Time for a new normal in beta-cell regeneration research[J].Diabet:A Jt Am Diabet Associat,2014(4):1198-1199.
[9] Jiang W,Shi Y,Zhao D,et al.In vitro derivation of functional insulin-producing cells from human embryonic stem cells[J].Cell Res,2007(4):333-344.
[10] Farilla L,Hui H,Bertolotto C,et al.Glucagon-like peptide-1promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats[J].Endocrinology,2002,143(11):4397-4408.
[11] Imai J,Katagiri H,Yamada T,et al.Regulation of pancreatic beta cell mass by neuronal signals from the liver[J].Science,2008,322(5905):1250-1254.
[12] Yi P,Park J S,Melton D A.Betatrophin:a hormone that controls pancreatic beta cell proliferation[J].Cell,2014,153(2):747-758.
[13] Suzuki A,Nakauchi H,Taniguchi H.Glucagon-like peptide 1(1-37)converts intestinal epithelial cells into insulin-producing cells[J].Proc Nat Acad Sci USA,2003,100(9):5034-5039.
[14] Kojima H,Nakamura T,Fujita Y,et al.Combined expression of pancreatic duodenal homeobox 1and islet factor 1induces immature enterocytes to produce insulin[J].Diabetes,2002,51(5):1398-1408.
[15] Miyawaki K,Kawaguchi M,Iwanaga T,et al.Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells[J].Proc Natl Acad Sci USA,2005,102(42):15116-15121.
[16] Rooman I,Heremans Y,Heimberg H,et al.Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro[J].Diabetologia,2000,43(7):907-914.
[17] Sosapineda B,Chowdhury K,Torres M,et al.The Pax4gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas[J].Nature,1997,386(6623):399-402.
[18] Collombat P,Mansouri A,Hecksher-Sorensen J,et al.Opposing actions of Arx and Pax4in endocrine pancreas development[J].Genes Dev,2003,17(20):2591-2603.
[19] Prado C L,Pugh-Bernard A E,Elghazi L,et al.Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development[J].Proc Nat Acad Sci USA,2004,101(9):2924-2929.
[20] Horb M E,Shen C N,Tosh D,et al.Experimental conversion of liver to pancreas[J].Curr Biol,2003,13(2):105-115.
[21] Jarikji Z,Vanamala S,Beck C,et al.Differential abili'ty of Ptf1aand Ptf1a-VP16to convert stomach,duodenum and liver to pancreas[J].Develop Biol,2007,304(2):786-799.
[22] Kaneto H,Matsuoka T A,Nakatani Y,et al.A crucial role of MafA as a novel therapeutic target for diabetes.[J].J Biol Chem,2005,280(15):15047-15052.
[23] Kojima H,Fujimiya M,Matsumura K,et al.NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice[J].Nature Med,2003,9(5):596-603.
[24] Collombat P,Hecksher-Sorensen J,Krull J,et al.Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression[J].J Clin Investigat,2007,117(4):961-970.
[25] Collombat P,Xu X,Ravassard P,et al.The ectopic expression of Pax4in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells[J].Cell,2009,138(3):449-462.
[26] Courtney M,Pfeifer A,Al-Hasani K,et al.In vivo conversion of adultαcells intoβ-like cells:a new research avenue in the context of type 1diabetes[J].Diabet Obesity Metab,2011,13(s1):47-52.
[27] Gromada J,Franklin I,Wollheim C B.Alpha-cells of the endocrine pancreas:35years of research but the enigma remains[J].Endocrine Rev,2007,28(1):84-116.
[28]刘英,江霞.糖尿病细胞治疗的研究进展[J].中华细胞与干细胞杂志,2017(1):59-63.
[29] Ben-Othman N,Vieira A,Courtney M,et al.Long-term GABA administration induces alpha cell-mediated beta-like cell neogenesis[J].Cell,2016,168(1-2):73-85.
[30] Li J,Casteels T,Frogne T,et al.Artemisinins target GABAA receptor signaling and impair alpha cell identity[J].Cell,2016,168(1-2):86-100.
[31] Hao W,Mahato R I.Beta cell regeneration:A novel strategy for treating type 1diabetes[J].Gene Technol,2013,2(1):e106.
[2]宋光艳.抗糖尿病药物的临床应用[J].中国保健营养,2016,26(22):206.
[3] Wang L,Gao P,Zhang M,et al.Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013[J].JAMA,2017,317(24):2515.
[4]王鹤霏.脂肪间充质干细胞治疗大鼠I型糖尿病的效果及机理探讨[D].内蒙古呼和浩特:内蒙古大学,2016.
[5] Aguayomazzucato C,Bonnerweir S.Pancreaticβcell regeneration as a possible therapy for diabetes.[J].Cell Metabolism,2017,27(1):57-67.
[6]张辰,赵振民,张翔宇,等.干细胞诱导分化为产胰岛素细胞的研究进展[J].现代生物医学进展,2016,16(7):1350-1353.
[7]朱剑,刘超.胰岛β细胞再生——糖尿病治疗的新思路[J].国际内分泌代谢杂志,2008,28(1):48-52.
[8] Stewart A F.Betatrophin versus bitter-trophin and the elephant in the room:Time for a new normal in beta-cell regeneration research[J].Diabet:A Jt Am Diabet Associat,2014(4):1198-1199.
[9] Jiang W,Shi Y,Zhao D,et al.In vitro derivation of functional insulin-producing cells from human embryonic stem cells[J].Cell Res,2007(4):333-344.
[10] Farilla L,Hui H,Bertolotto C,et al.Glucagon-like peptide-1promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats[J].Endocrinology,2002,143(11):4397-4408.
[11] Imai J,Katagiri H,Yamada T,et al.Regulation of pancreatic beta cell mass by neuronal signals from the liver[J].Science,2008,322(5905):1250-1254.
[12] Yi P,Park J S,Melton D A.Betatrophin:a hormone that controls pancreatic beta cell proliferation[J].Cell,2014,153(2):747-758.
[13] Suzuki A,Nakauchi H,Taniguchi H.Glucagon-like peptide 1(1-37)converts intestinal epithelial cells into insulin-producing cells[J].Proc Nat Acad Sci USA,2003,100(9):5034-5039.
[14] Kojima H,Nakamura T,Fujita Y,et al.Combined expression of pancreatic duodenal homeobox 1and islet factor 1induces immature enterocytes to produce insulin[J].Diabetes,2002,51(5):1398-1408.
[15] Miyawaki K,Kawaguchi M,Iwanaga T,et al.Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells[J].Proc Natl Acad Sci USA,2005,102(42):15116-15121.
[16] Rooman I,Heremans Y,Heimberg H,et al.Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro[J].Diabetologia,2000,43(7):907-914.
[17] Sosapineda B,Chowdhury K,Torres M,et al.The Pax4gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas[J].Nature,1997,386(6623):399-402.
[18] Collombat P,Mansouri A,Hecksher-Sorensen J,et al.Opposing actions of Arx and Pax4in endocrine pancreas development[J].Genes Dev,2003,17(20):2591-2603.
[19] Prado C L,Pugh-Bernard A E,Elghazi L,et al.Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development[J].Proc Nat Acad Sci USA,2004,101(9):2924-2929.
[20] Horb M E,Shen C N,Tosh D,et al.Experimental conversion of liver to pancreas[J].Curr Biol,2003,13(2):105-115.
[21] Jarikji Z,Vanamala S,Beck C,et al.Differential abili'ty of Ptf1aand Ptf1a-VP16to convert stomach,duodenum and liver to pancreas[J].Develop Biol,2007,304(2):786-799.
[22] Kaneto H,Matsuoka T A,Nakatani Y,et al.A crucial role of MafA as a novel therapeutic target for diabetes.[J].J Biol Chem,2005,280(15):15047-15052.
[23] Kojima H,Fujimiya M,Matsumura K,et al.NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice[J].Nature Med,2003,9(5):596-603.
[24] Collombat P,Hecksher-Sorensen J,Krull J,et al.Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression[J].J Clin Investigat,2007,117(4):961-970.
[25] Collombat P,Xu X,Ravassard P,et al.The ectopic expression of Pax4in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells[J].Cell,2009,138(3):449-462.
[26] Courtney M,Pfeifer A,Al-Hasani K,et al.In vivo conversion of adultαcells intoβ-like cells:a new research avenue in the context of type 1diabetes[J].Diabet Obesity Metab,2011,13(s1):47-52.
[27] Gromada J,Franklin I,Wollheim C B.Alpha-cells of the endocrine pancreas:35years of research but the enigma remains[J].Endocrine Rev,2007,28(1):84-116.
[28]刘英,江霞.糖尿病细胞治疗的研究进展[J].中华细胞与干细胞杂志,2017(1):59-63.
[29] Ben-Othman N,Vieira A,Courtney M,et al.Long-term GABA administration induces alpha cell-mediated beta-like cell neogenesis[J].Cell,2016,168(1-2):73-85.
[30] Li J,Casteels T,Frogne T,et al.Artemisinins target GABAA receptor signaling and impair alpha cell identity[J].Cell,2016,168(1-2):86-100.
[31] Hao W,Mahato R I.Beta cell regeneration:A novel strategy for treating type 1diabetes[J].Gene Technol,2013,2(1):e106.