珍奥双迪(大连)健康产业集团有限公司

40.腺嘌呤核苷酸及代谢产物在调节糖脂代谢稳态中的作用

1.Antonioli L,Blandizzi C,Pacher P,Haskó G.Immunity,

inflammation and cancer:a leading role for adenosine.Nat

Rev Cancer 2013;13(12):842–857.

2.Antonioli L,Colucci R,Pellegrini C,Giustarini G, Tuccori M,BlandizziC,Fornai M.The role of purinergic pathways in the pathophysiology of gutdiseases:pharmacological modulation and potential therapeuticapplications.Pharmacol Ther 2013;139(2):157–188.

3.Di Virgilio F,Adinolfi E.Extracellular purines, purinergic receptors andtumor growth.Oncogene 2017;36(3):293–303.

4.Antonioli L,Blandizzi C,Csoka B,Pacher P,Hasko G.

Adenosine signalling in diabetes mellitus--pathophysiology and therapeuticconsiderations.Nat Rev Endocrinol 2015;11(4):228–241.

5.Ralevic V,Burnstock G.Receptors for purines and pyrimidines.Pharmacol Rev1998;50(3):413–492.

6.Burnstock G.Purine and pyrimidine receptors.Cell Mol

Life Sci 2007;64(12):1471–1483.

7.Burnstock G,Novak I.Purinergic signalling and diabetes. Purinergic Signal2013;9(3):307–324.

8.Schwiebert EM,Zsembery A.Extracellular ATP as a

signaling molecule for epithelial cells.Biochim Biophys

Acta 2003;1615(1–2):7–32.

9.Deaglio S,Dwyer KM,Gao W,Friedman D,Usheva A,

Erat A,Chen JF,Enjyoji K,Linden J,Oukka M,Kuchroo

VK,Strom TB,Robson SC.Adenosine generation

catalyzed by CD39 and CD73 expressed on regulatory T

cells mediates immune suppression.J Exp Med 2007;

204(6):1257–1265.

10.Clayton A,Al-Taei S,Webber J,Mason MD,Tabi Z.Cancer

exosomes express CD39 and CD73,which suppress T cells

through adenosine production.J Immunol 2011;187(2):676–683.

11.Antonioli L,Pacher P,Vizi ES,Haskó G.CD39 and CD73

in immunity and inflammation.Trends Mol Med 2013;19(6): 355–367.

12.Eltzschig HK,Kohler D,Eckle T,Kong T,Robson SC,Colgan SP.Central role ofSp1-regulated CD39 in hypoxia/ischemia protection.Blood 2009;113(1):224–232.

13.Synnestvedt K,Furuta GT,Comerford KM,Louis N,Karhausen J,EltzschigHK,Hansen KR,Thompson LF, Colgan SP.Ecto-5'-nucleotidase(CD73)regulation byhypoxia-inducible factor-1 mediates permeability changes

in intestinal epithelia.J Clin Invest 2002;110(7):993

1002.

14.Antonioli L,Fornai M,Colucci R,Ghisu N,Tuccori M,

Del Tacca M,Blandizzi C.Regulation of enteric functions

by adenosine:pathophysiological and pharmacological

implications.Pharmacol Ther 2008;120(3):233–253.

15.Antonioli L,Colucci R,La Motta C,Tuccori M,Awwad O,

Da Settimo F,Blandizzi C,Fornai M.Adenosine deaminase

in the modulation of immune system and its potential as a

novel target for treatment of inflammatory disorders.Curr

Drug Targets 2012;13(6):842–862.

16.Fredholm BB,AP IJ,Jacobson KA,Klotz KN,Linden J.International Union ofPharmacology.XXV.Nomenclature and classification of adenosinereceptors.Pharmacol Rev

2001;53(4):527–552.

17.Fredholm BB,AP IJ,Jacobson KA,Linden J,Muller CE. International Union ofBasic and Clinical Pharmacology. LXXXI.Nomenclature and classification ofadenosine receptors--an update.Pharmacol Rev 2011;63(1):1–34.

18.Tsushima Y,Nishizawa H,Tochino Y,Nakatsuji H,Sekimoto R, NagaoH,Shirakura T,Kato K,Imaizumi K,Takahashi H, Tamura M,Maeda N,FunahashiT,Shimomura I.Uric acid secretion from adipose tissue and its increase inobesity.J Biol Chem 2013;288(38):27138–27149.

19.Hikita M,Ohno I,Mori Y,Ichida K,Yokose T,Hosoya T.

Relationship between hyperuricemia and body fat distribution.Intern Med2007;46(17):1353–1358.

20.Tamba S,Nishizawa H,Funahashi T,Okauchi Y,Ogawa T, Noguchi M,Fujita K,RyoM,Kihara S,Iwahashi H,Yamagata K, Nakamura T,Shimomura I,MatsuzawaY.Relationship between the serum uric acid level, visceral fat accumulation andserum adiponectin concentration in Japanese men.Intern Med 2008;47(13):1175–1180.

21.Kim TH,Lee SS,Yoo JH,Kim SR,Yoo SJ,Song HC,Kim YS,Choi EJ,Kim YK.Therelationship between the regional abdominal adipose tissue distribution and theserum uric acid levels in people with type 2 diabetes mellitus.Diabetol MetabSyndr 2012;4(1):3.

22.Rathmann W,Haastert B,Icks A,Giani G,Roseman JM. Ten-year change inserum uric acid and its relation to

changes in other metabolic risk factors in young black and

white adults:the CARDIA study.Eur J Epidemiol 2007; 22(7):439–445.

23.Coutinho Tde A,Turner ST,Peyser PA,Bielak LF,Sheedy PF 2nd,KulloIJ.Associations of serum uric acid with markers of inflammation,metabolicsyndrome,and subclinical coronary atherosclerosis.Am J Hypertens 2007;20(1):83–89.24 Lin SD,TsaiDH,Hsu SR.Association between serum uric

acid level and components of the metabolic syndrome.J

Chin Med Assoc 2006;69(11):512–516.

25.Cornier MA, Dabelea D,Hernandez TL,Lindstrom RC,Steig AJ,Stob NR,VanPelt RE,Wang H,Eckel RH.The metabolic syndrome.Endocr Rev 2008;29(7):777–822.

26.Matsuzawa Y,Funahashi T,Nakamura T.The concept of

Metabolic syndrome:contribution of visceral fat accumulation and itsmolecular mechanism.J Atheroscler Thromb 2011;18(8):629–639.

27.Kodama S,Saito K,Yachi Y,Asumi M,Sugawara A,Totsuka

K,Saito A,Sone H.Association between serum uric acid

and development of type 2 diabetes.Diabetes Care 2009;

32(9):1737–1742.

28.Lv Q,Meng XF,He FF,Chen S,Su H,Xiong J,Gao P,Tian XJ, Liu JS,ZhuZH,Huang K,Zhang C.High serum uric acid and increased risk of type 2 diabetes:asystemic review and meta-analysis of prospective cohort studies.PLoS One2013;8(2):e56864.

29.Zhang Y,Wang Z,Zhao Y,Zhao M,Wang S,Hua Z,Zhang

J.The plasma 5'-AMP acts as a potential upstream regulator

of hyperglycemia in type 2 diabetic mice.Am J Physiol Endocrinol Metab2012;302(3):E325–E333.

30.Yang X,Zhao Y,Sun Q,Yang Y,Gao Y,Ge W,Liu J,Xu X,Zhang J.An intermediaryrole of adenine nucleotides on free fatty acids-induced hyperglycemia in obesemice.Front Endocrinol (Lausanne) 2019;10:497.

31.Sailaja YR,Baskar R,Saralakumari D.The antioxidant

status during maturation of reticulocytes to erythrocytes in type 2diabetics.Free Radic Biol Med 2003;35(2):133–139.

32.Bergfeld GR,Forrester T.Release of ATP from human

erythrocytes in response to a brief period of hypoxia and

hypercapnia.Cardiovasc Res 1992;26(1):40–47.

33.Sprague RS,Ellsworth ML,Stephenson AH,Kleinhenz

ME,Lonigro AJ.Deformation-induced ATP release from

red blood cells requires CFTR activity.Am J Physiol 1998; 275(5):H1726–H1732.

34.Tsuneki H,Ishizuka M,Terasawa M,Wu JB,Sasaoka T,

Kimura I.Effect of green tea on blood glucose levels and

serum proteomic patterns in diabetic (db/db) mice and on

glucose metabolism in healthy humans. BMC Pharmacol 2004;4:18.

35.Yang X,Zhao Y,Sun Q,Yang Y,Gao Y,Ge W,Liu J,Xu X,

Weng D,Wang S, Zhang J.Adenine nucleotide-mediated

regulation of hepatic PTP1B activity in mouse models of

type 2 diabetes.Diabetologia 2019;62(11):2106–2117.

36.Choi HK,Ford ES.Prevalence of the metabolic syndrome

in individuals with hyperuricemia.Am J Med 2007;120(5): 442–447.

37.Lunkes GI,Lunkes D,Stefanello F,Morsch A, Morsch

VM,Mazzanti CM,Schetinger MR.Enzymes that hydrolyze

adenine nucleotides in diabetes and associated pathologies. Thromb Res2003;109(4):189–194.

38.Lee JG,Kang DG,Yu JR,Kim Y,Kim J,Koh G, Lee D.Changes in adenosinedeaminase activity in patients with type 2 diabetes mellitus and effect ofDPP-4 inhibitor treatment on ADA activity. Diabetes Metab J 2011;35(2):149–158.

39.Kurtul N,Pence S,Akarsu E,Kocoglu H,Aksoy Y,Aksoy

H.Adenosine deaminase activity in the serum of type 2

diabetic patients.Acta Medica(Hradec Kralove)2004;47(1):

33–35.

40.Garcia-Hernandez MH, Portales-Cervantes L, Cortez-EspinosaN,Vargas-Morales JM,Fritche Salazar JF,Rivera-Lopez E,Rodriguez-RiveraJG,Quezada-Calvillo R, Portales-Perez DP.Expression and function of P2X7receptor and CD39/Entpd1 in patients with type 2 diabetes and their associationwith biochemical parameters. Cell Immunol 2011;269(2):135–143.

41.Narravula S,Lennon PF,Mueller BU,Colgan SP.Regula-tion of endothelialCD73 by adenosine: paracrine pathway for enhanced endothelial barrier function.J Immunol 2000; 165(9):5262–5268.

42.Larijani B,Heshmat R,Ebrahimi-Rad M,Khatami S,

Valadbeigi S,Saghiri R.Diagnostic value of adenosine

deaminase and its isoforms in type II diabetes mellitus. Enzyme Res2016;2016:9526593.

43.Hoshino T,Yamada K,Masuoka K,Tsuboi I,Itoh K,Nonaka

K,Oizumi K.Elevated adenosine deaminase activity in the

serum of patients with diabetes mellitus.Diabetes Res Clin

Pract 1994;25(2):97–102.

44.Bottini E,Gloria-Bottini F.Adenosine deaminase and body mass index innon-insulin-dependent diabetes mellitus. Metabolism 1999;48(8):949–951.

45.Bottini N,Gloria-Bottini F,Borgiani P,Antonacci E,

Lucarelli P,Bottini E.Type 2 diabetes and the genetics of

signal transduction:a study of interaction between adenosine deaminase andacid phosphatase locus 1 polymorphisms.Metabolism 2004;53(8):995–1001.

46.Xu C,Wan X,Xu L,Weng H,Yan M,Miao M,Sun Y,Xu G,Dooley S,Li Y,YuC.Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia:Onestone hits two birds.J Hepatol 2015;62(6):1412–1419.

47.Cheung KJ,Tzameli I,Pissios P,Rovira I,Gavrilova O,

Ohtsubo T,Chen Z,Finkel T,Flier JS,Friedman JM. Xanthine oxidoreductase isa regulator of adipogenesis and

PPARgamma activity.Cell Metab 2007;5(2):115–128.

48.Oberbach A,Neuhaus J,Schlichting N,Kugler J,Baumann

S,Till H.Sleeve gastrectomy reduces xanthine oxidase and

uric acid in a rat model of morbid obesity.Surg Obes Relat

Dis 2014;10(4):684–690.

49.Glas R, Sauter NS, Schulthess FT, Shu L, Oberholzer J,

Maedler K. Purinergic P2X7 receptors regulate secretion of

interleukin-1 receptor antagonist and beta cell function andsurvival.Diabetologia 2009;52(8):1579–1588.

50.Coutinho-Silva R,Robson T,Beales PE,Burnstock G. Changes in expressionof P2X7 receptors in NOD mouse

pancreas during the development of diabetes.Autoimmunity

2007;40(2):108–116.

51.Chen YG,Scheuplein F,Driver JP,Hewes AA,Reifsnyder

PC,Leiter EH,Serreze DV.Testing the role of P2X7 receptors

in the development of type 1 diabetes in nonobese diabetic

mice.J Immunol 2011;186(7):4278–4284.

52.Thompson BA,Storm MP,Hewinson J,Hogg S,Welham

MJ,MacKenzie AB.A novel role for P2X7 receptor signalling in the survivalof mouse embryonic stem cells.Cell Signal 2012;24(3):770–778.

53.Zhang XJ (张秀军),Zheng GG,Ma XT,Lin YM,Song YH,Wu KF.Effects ofvarious inducers on the expression of P2X7 receptor in human peripheral bloodmononuclear cells.Acta Physiol Sin (生理学报)2005;57(2):193–198(in Chinese).54 Yip L,TaylorC,Whiting CC,Fathman CG.Diminished adenosine A1 receptor expression inpancreatic alpha-cells may contribute to the pathology of type 1 diabetes.Diabetes

2013;62(12):4208–4219.

55.Guzman-Flores JM,Cortez-Espinosa N,Cortes-Garcia JD, Vargas-MoralesJM,Catano-Canizalez YG,RodriguezRivera JG,Portales-Perez DP.Expression of CD73and A2A receptors in cells from subjects with obesity and type 2 diabetesmellitus.Immunobiology 2015;220(8):976–984.

56.Liu IM,Tzeng TF,Tsai CC,Lai TY,Chang CT,Cheng JT.Increase in adenosineA1 receptor gene expression in the

liver of streptozotocin-induced diabetic rats.Diabetes

Metab Res Rev 2003;19(3):209–215.

57.Grden M,Podgorska M,Szutowicz A,Pawelczyk T.Diabetesinduced alterationsof adenosine receptors expression level in rat liver.Exp Mol Pathol2007;83(3):392–398.

58.Johnston-Cox H,Koupenova M,Yang D,Corkey B,Gokce

N,Farb MG,LeBrasseur N,Ravid K.The A2b adenosine receptor modulates glucosehomeostasis and obesity.PLoS One 2012;7(7):e40584.

59.Burnstock G,Vaughn B,Robson SC.Purinergic signalling

in the liver in health and disease.Purinergic Signal 2013;

10(1):51–70.

60.Delmas-Beauvieux MC,Gallis JL,Clerc M,Canioni P.31P

NMR studies of rat liver cold preservation with histidine-bufferedlactobionate solution.Cryobiology 1993;30(6):551–561.

61.Häussinger D,Stehle T,Gerok W,Tran-Thi TA,Decker K.

Hepatocyte heterogeneity in response to extracellular ATP.

Eur J Biochem 1987;169(3):645–650.

62.Keppens S,De Wulf H.P2-purinergic control of liver

glycogenolysis.Biochem J 1985;231(3):797–799.

63.Keppens S,De Wulf H.Characterization of the liver P2-

purinoceptor involved in the activation of glycogen phosphorylase.Biochem J1986;240(2):367–371.

64.Keppens S,Vandekerckhove A,De Wulf H.Characterization

of the purinoceptors present in rabbit and guinea pig liver. Eur JPharmacol 1990;182(1):149–153.

65.Fischer L,Haag-Diergarten S,Scharrer E,Lutz TA. Leukotriene andpurinergic receptors are involved in the

hyperpolarizing effect of glucagon in liver cells. Biochim

Biophys Acta 2005;1669(1):26–33.

66.Dixon CJ,Hall JF,Webb TE,Boarder MR.Regulation of

rat hepatocyte function by P2Y receptors:focus on control

of glycogen phosphorylase and cyclic AMP by 2-methylth-ioadenosine5'-diphosphate.J Pharmacol Exp Ther 2004;311(1):334–341.

67.Dixon CJ,White PJ,Hall JF,Kingston S,Boarder MR. Regulation of humanhepatocytes by P2Y receptors:control

of glycogen phosphorylase,Ca2+,and mitogen-activated

protein kinases.J Pharmacol Exp Ther 2005;313(3):1305–1313.

68.Sit KH,Bay BH,Wong KP.Extracellular ATP induces

rapid cell rounding in cultured human Chang liver cells. Jpn J Physiol 1992;42(2):355–362.

69.Koike M,Kashiwagura T,Takeguchi N.Gluconeogenesis

stimulated by extracellular ATP is triggered by the initial

increase in the intracellular Ca2+ concentration of the

periphery of hepatocytes.Biochem J 1992;283(Pt 1)(Pt

1):265–272.

70.Asensi M,Lopez-Rodas A,Sastre J,Viña J,Estrela JM.

Inhibition of gluconeogenesis by extracellular ATP in

isolated rat hepatocytes.Am J Physiol 1991;261(6 Pt 2): R1522–R1526.

71.Probst I,Quentmeier A,Schweickhardt C,Unthan-Fechner

K.Stimulation by insulin of glycolysis in cultured hepatocytes isattenuated by extracellular ATP and puromycin through purine-dependentinhibition of phosphofructokinase 2 activation.Eur J Biochem 1989;182(2):387–393.

72.Tahani H,Samia M,Rizk S, Habib YA,Tallaat M. Effect of

repeated doses of ATP on serum protein pattern and fat

content of the liver in experimental diabetes.Z Ernahrungswiss1977;16(2):120–127.

73.Wang C,Geng B,Cui Q,Guan Y,Yang J.Intracellular and

extracellular adenosine triphosphate in regulation of insulin secretionfrom pancreatic βcells (β).J Diabetes 2014;6(2):113–119.

74.Squires PE,James RF,London NJ,Dunne MJ.ATPinduced intracellular Ca2+signals in isolated human insulinsecreting cells.Pflugers Arch 1994;427(1–2):181–183.

75.Petit P,Lajoix AD,Gross R.P2 purinergic signalling in the pancreaticbeta-cell:control of insulin secretion and pharmacology.Eur J Pharm Sci2009;37(2):67–75.

76.Richards-Williams C,Contreras JL,Berecek KH,Schwiebert EM.ExtracellularATP and zinc are co-secreted with insulin and activate multiple P2X purinergicreceptor channels expressed by islet beta-cells to potentiate insulinsecretion.Purinergic Signal 2008;4(4):393–405.

77.Coutinho-Silva R,Parsons M,Robson T,Burnstock G. Changes in expressionof P2 receptors in rat and mouse

pancreas during development and ageing.Cell Tissue Res

2001;306(3):373–383.

78.Coutinho-Silva R,Parsons M,Robson T,Lincoln J,Burnstock G.P2X and P2Ypurinoceptor expression in pancreas from streptozotocin-diabetic rats.Mol CellEndocrinol 2003;204(1–2):141–154.

79.Petit P,Manteghetti M,Puech R,Loubatieres-Mariani MM. ATP andphosphate-modified adenine nucleotide analogues.

Effects on insulin secretion and calcium uptake.Biochem

Pharmacol 1987;36(3):377–380.

80.Jacques-Silva MC,Correa-Medina M,Cabrera O,Rodriguez-Diaz R,MakeevaN,Fachado A,Diez J,Berman DM, Kenyon NS,Ricordi C,Pileggi A,Molano RD, BerggrenPO, Caicedo A.ATP-gated P2X3 receptors constitute a positive autocrine signalfor insulin release in the human pancreatic beta cell.Proc Natl Acad Sci U S A2010; 107(14):6465–6470.

81.Silva AM,Rodrigues RJ,Tome AR,Cunha RA, Misler S,

Rosario LM,Santos RM.Electrophysiological and immunocytochemical evidencefor P2X purinergic receptors in pancreatic beta cells.Pancreas 2008;36(3):279–283.

82.Santini E,Cuccato S,Madec S,Chimenti D,Ferrannini E,

Solini A.Extracellular adenosine 5'-triphosphate modulates insulinsecretion via functionally active purinergic receptors of X and Ysubtype.Endocrinology 2009;150(6):2596–2602.

83.Parandeh F,Abaraviciene SM,Amisten S,Erlinge D,Salehi

A.Uridine diphosphate (UDP) stimulates insulin secretion

by activation of P2Y6 receptors.Biochem Biophys Res Commun 2008;370(3):499–503.

84.Ohtani M,Suzuki J,Jacobson KA,Oka T.Evidence for the

possible involvement of the P2Y6 receptor in Ca2+ mobilizationand insulin secretion in mouse pancreatic islets.Purinergic Signal2008;4(4):365–375.

85.Madsen R,Banday VS,Moritz T,Trygg J,Lejon K.Altered

metabolic signature in pre-diabetic NOD mice.PLoS One

2012;7(4):e35445.

86.Vieira FS,Nanini HF,Takiya CM,Coutinho-Silva R.P2X7

receptor knockout prevents streptozotocin-induced type 1

diabetes in mice.Mol Cell Endocrinol 2016;419:148–157.

87.Todd JN,Poon W,Lyssenko V,Groop L,Nichols B,Wilmot

M,Robson S,Enjyoji K,Herman MA,Hu C,Zhang R,Jia W,Ma R, Florez JC,FriedmanDJ.Variation in glucose homeostasis traits associated with P2RX7 polymorphismsin mice and humans.J Clin Endocrinol Metab 2015;100(5):E688–E696.88 LeonC,Freund M,Latchoumanin O,Farret A,Petit P,Cazenave JP,Gachet C.The P2Y1receptor is involved in the maintenance of glucose homeostasis and in insulinsecretion in mice.Purinergic Signal 2005;1(2):145–151.

89.Bollen M,Keppens S,Stalmans W.Specific features of

glycogen metabolism in the liver.Biochem J 1998;336(Pt

1)(Pt 1):19–31

90.Andersson O.Role of adenosine signalling and metabolism

in β-cellregeneration.Exp Cell Res 2014;321(1):3–10.

91.Koupenova M,Ravid K.Adenosine,adenosine receptors and their role inglucose homeostasis and lipid metabolism.J Cell Physiol 2013:10.1002/jcp.24352.

92.Eisenstein A,Ravid K.G protein-coupled receptors and

adipogenesis:a focus on adenosine receptors.J Cell Physiol

2014;229(4):414–421.

93.Gharibi B,Abraham AA,Ham J,Evans BA.Contrasting effects of A1 and A2badenosine receptors on adipogenesis.

Int J Obes (Lond) 2012;36(3):397–406.

94.Dong Q,Ginsberg HN,Erlanger BF.Overexpression of the

A1 adenosine receptor in adipose tissue protects mice from

obesity-related insulin resistance. Diabetes Obes Metab

2001;3(5):360–366.

95.Ohtani M,Oka T,Ohura K.Possible involvement of A2A

and A3 receptors in modulation of insulin secretion and

beta-cell survival in mouse pancreatic islets.Gen Comp

Endocrinol 2013;187:86–94.

96.Chhabra P,Wang K,Zeng Q,Jecmenica M,Langman L,Linden J,KetchumRJ,Brayman KL.Adenosine A2A agonist administration improves islet transplantoutcome:Evidence for the role of innate immunity in islet graft rejection. CellTransplant 2010;19(5):597–612.

97.Nemeth ZH, Bleich D,Csoka B,Pacher P,Mabley JG,Himer L,Vizi ES,DeitchEA,Szabo C,Cronstein BN,Hasko G.Adenosine receptor activation ameliorates type1 diabetes.FASEB J 2007;21(10):2379–2388.

98.Chia JS,McRae JL,Thomas HE,Fynch S,Elkerbout L,Hill P,Murray-SegalL,Robson SC,Chen JF,d'Apice AJ,Cowan PJ,Dwyer KM.The protective effects of CD39overexpression in multiple low-dose streptozotocininduced diabetes inmice.Diabetes 2013;62(6):2026–2035.

99.Verspohl EJ,Johannwille B,Waheed A,Neye H.Effect of

purinergic agonists and antagonists on insulin secretion

from INS-1 cells (insulinoma cell line) and rat pancreatic

islets.Can J Physiol Pharmacol 2002;80(6):562–568.

100.Johansson SM,Salehi A,Sandström ME,Westerblad H, Lundquist I,CarlssonPO,Fredholm BB,Katz A.A1 receptor

deficiency causes increased insulin and glucagon secretion

in mice.Biochem Pharmacol 2007;74(11):1628–1635.

101.Patinha D,Abreu C,Carvalho C,Cunha OM,Mota M,Afonso J, SousaT,Albino-Teixeira A,Diniz C,Morato M.Adenosine A2A and A3 receptors as targetsfor the treatment of hypertensive-diabetic nephropathy.Biomedicines 2020;8(11):529.

102.Longhi MS,Robson SC,Bernstein SH,Serra S,Deaglio S.

Biological functions of ecto-enzymes in regulating extracellular adenosinelevels in neoplastic and inflammatory disease states.J Mol Med (Berl)2013;91(2):165–172.

103.Xia L,Wang ZQ,Zhang Y,Yang X,Zhan YB, Cheng R,Wang SM,ZhangJF.Reciprocal regulation of insulin and plasma 5'-AMP in glucose homeostasis inmice.J Endocrinol 2015;224(3):225–234.

104.Shao J,Yamashita H,Qiao L,Friedman JE.Decreased Akt

kinase activity and insulin resistance in C57BL/KsJLeprdb/db mice.JEndocrinol 2000;167(1):107–115.

105.Whiteman EL,Cho H,Birnbaum MJ.Role of Akt/protein

kinase B in metabolism.Trends Endocrinol Metab 2002; 13(10):444–451.

106.Guo S.Insulin signaling,resistance,and the metabolic

syndrome:insights from mouse models into disease mechanisms.J Endocrinol2014;220(2):T1–T23.

107.Busa WB,Nuccitelli R.Metabolic regulation via intracellular pH.Am JPhysiol 1984;246(4 Pt 2):R409–R438.

108.Ritter M,Wöll E,Häussinger D,Lang F.Effects of bradykinin on cellvolume and intracellular pH in NIH 3T3 fibroblasts expressing the ras oncogene.FEBS Lett 1992; 307(3):367–370.

109.Edmonds BT,Murray J,Condeelis J.pH regulation of the

F-actin binding properties of Dictyostelium elongation

factor 1 alpha.J Biol Chem 1995;270(25):15222–15230.

110.Nosek TM,Fender KY,Godt RE.It is diprotonated inorganic phosphate thatdepresses force in skinned skeletal muscle fibers.Science 1987;236(4798):191–193.111 Hao W,LuoZ,Zheng L,Prasad K,Lafer EM.AP180 and

AP-2 interact directly in a complex that cooperatively

assembles clathrin.J Biol Chem 1999;274(32):22785–22794.

112.Li X,Galli T,Leu S,Wade JB,Weinman EJ,Leung G, Cheong A,LouvardD,Donowitz M.Na+-H+exchanger 3(NHE3) is present in lipidrafts in the rabbit ileal brush border:a role for rafts in trafficking andrapid stimulation of NHE3.J Physiol 2001;537(Pt 2):537–552.

113.Yan W,Nehrke K,Choi J,Barber DL.The Nck-interacting

kinase(NIK)phosphorylates the Na+-H+exchanger NHE1and regulates NHE1 activation by platelet-derived growth factor.J Biol Chem2001;276(33):31349–31356.114 Kaloyianni M,Bourikas D,Koliakos G.The effectof insulin

on Na+-H+ antiport activity of obese and normalsubjects

erythrocytes.Cell Physiol Biochem 2001;11(5):253–258.

115.Aharonovitz O,Granot Y.Stimulation of mitogen-activated protein kinaseand Na+-H+ exchanger in human platelets.Differentialeffect of phorbol ester and vasopressin.J Biol Chem 1996;271(28):16494–16499.

116.Yip JW,Ko WH,Viberti G,Huganir RL,Donowitz M,Tse

CM.Regulation of the epithelial brush border Na+-H+ exchangerisoform 3 stably expressed in fibroblasts by

fibroblast growth factor and phorbol esters is not through

changes in phosphorylation of the exchanger.J Biol Chem

1997;272(29):18473–18480.

117.Xia L,Ma SH,Zhang Y,Wang T,Zhou MY,Wang ZQ,Zhang JF.Daily variation inglobal and local DNA methyl ation in mouse livers.PLoS One 2015;10(2):e0118101.

118.Enneman AW,van der Velde N,de Jonge R,Heil SG,Stolk

L,Hofman A,Rivadeneira F,Zillikens MC,Uitterlinden AG, van Meurs JB.Theassociation between plasma homo Cysteine levels,methylation capacity andincident osteoporotic fractures.Bone 2012;50(6):1401–1405.

119.Poirier LA,Brown AT,Fink LM,Wise CK,Randolph CJ, Delongchamp RR,FonsecaVA.Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabeticnephropathy.Metabolism 2001;50(9):1014–1018.

120.Ratnam S,Wijekoon EP,Hall B,Garrow TA,Brosnan ME, Brosnan JT.Effects ofdiabetes and insulin on betaine

homocysteine S-methyltransferase expression in rat liver.

Am J Physiol Endocrinol Metab 2006;290(5):E933–E939.121 Becker A,HenryRM,Kostense PJ,Jakobs C,Teerlink T,Zweegman S,Dekker JM, Nijpels G,HeineRJ,Bouter LM,Smulders YM,Stehouwer CD.Plasma homocysteine andS-adenosylmethionine in erythrocytes as determinants of carotid intima-mediathickness:different effects in diabetic and non-diabetic individuals.The HoornStudy.Atherosclerosis 2003;169(2):323–330.122 Cuyas E,Fernandez-ArroyoS,Verdura S,Garcia RA,Stursa J,Werner L,Blanco-Gonzalez E,Montes-Bayon M,JovenJ,Viollet B,Neuzil J,Menendez JA.Metformin regulates global DNA methylation viamitochondrial one-carbon metabolism. Oncogene 2018;37(7):963–970.

123.Bansal A,Pinney SE.DNA methylation and its role in the

pathogenesis of diabetes.Pediatr Diabetes 2017;18(3):

167–177.

124.Shen F,Huang W,Huang JT,Xiong J,Yang Y,Wu K,Jia GF,Chen J,Feng YQ,YuanBF,Liu SM.Decreased N6 -methyladenosine in peripheral blood RNA from diabeticpatients is associated with FTO expression rather than ALKBH5. J ClinEndocrinol Metab 2015;100(1):E148–E154.

125.Xue W,Huang J,Chen H,Zhang Y,Zhu X,Li J,Zhang W,Yuan Y,Wang Y,ZhengL,Huang K.Histone methyltransferase G9a modulates hepatic insulin signaling viaregulating HMGA1.Biochim Biophys Acta Mol Basis Dis 2018;1864(2):338–346.

126.Liu XY,Li H.Reduced Histone H3 lysine 9 methylation

contributes to the pathogenesis of latent autoimmune

diabetes in adults via regulation of SUV39H2 and KDM4C.

J Diabetes Res 2017;2017:8365762.

127.Ge W,Zhao Y,Yang Y,Ding Z,Xu X,Weng D,Wang S,Cheng R,Zhang J.Aninsulin-independent mechanism for transcriptional regulation of Foxo1 in type 2diabetic mice. J Biol Chem 2021;297(1):100846.

128.Esser N,Legrand-Poels S,Piette J,Scheen AJ,Paquot N.

Inflammation as a link between obesity, metabolic syn drome and type 2diabetes.Diabetes Res Clin Pract 2014;105(2):141–150.

129.Uysal KT,Wiesbrock SM,Marino MW,Hotamisligil GS.Protection fromobesity-induced insulin resistance in mice lacking TNF-alpha function.Nature1997;389(6651):610–614.

130.Wallenius V,Wallenius K,Ahrén B,Rudling M,Carlsten H,

Dickson SL,Ohlsson C,Jansson JO.Interleukin-6-deficient

mice develop mature-onset obesity.Nat Med 2002;8(1):75–79.

131.Stehouwer CD,Gall MA,Twisk JW,Knudsen E,Emeis JJ,Parving HH.Increasedurinary albumin excretion,endothelial dysfunction, and chronic low-gradeinflammation in type 2 diabetes:progressive,interrelated, and independentlyassociated with risk of death.Diabetes 2002;51(4):1157–1165.

132.Ofei F,Hurel S,Newkirk J,Sopwith M,Taylor R.Effects

of an engineered human anti-TNF-alpha antibody (CDP571) on insulinsensitivity and glycemic control in patients with NIDDM.Diabetes1996;45(7):881–885.

133.Dominguez H,Storgaard H,Rask-Madsen C,Steffen Hermann T,IhlemannN,Baunbjerg Nielsen D,Spohr C,Kober L,Vaag A,Torp-Pedersen C.Metabolic andvascular effects of tumor necrosis factor-alpha blockade with etaner cept inobese patients with type 2 diabetes.J Vasc Res 2005;42(6):517–525.

134.Paquot N,Castillo MJ,Lefèbvre PJ,Scheen AJ.No increased insulinsensitivity after a single intravenous

administration of a recombinant human tumor necrosis factor receptor:Fcfusion protein in obese insulin-resistant patients.J Clin Endocrinol Metab2000; 85(3):1316–1319.

135.Wu H,Nie Y,Xiong H,Liu S,Li G,Huang A,Guo L,Wang S,Xue Y,Wu B,PengL,Song M,Li G,Liang S.P2X7 receptor expression in peripheral blood monocytes iscorrelated with plasma C-reactive protein and cytokine levels in patients withtype 2 diabetes mellitus:a preliminary report.Inflammation2015;38(6):2076–2081.

136.Piccini A,Carta S,Tassi S,Lasiglié D,Fossati G,Rubartelli A.ATP isreleased by monocytes stimulated with pathogensensing receptor ligands andinduces IL-1beta and IL-18 secretion in an autocrine way.Proc Natl Acad Sci U SA 2008;105(23):8067–8072.

137.Chawla A,Nguyen KD,Goh YP.Macrophage-mediated

inflammation in metabolic disease.Nat Rev Immunol 2011;

11(11):738–749.

138.Csoka B,Koscso B,Toro G,Kokai E,Virag L,Nemeth ZH,Pacher P,Bai P,HaskoG.A2B adenosine receptors prevent insulin resistance by inhibiting adiposetissue inflammation via maintaining alternative macrophage activation.Diabetes2014;63(3):850–866.

139.CsókaB,Selmeczy Z,Koscsó B,NémethZH,Pacher P,Murray PJ,Kepka-Lenhart D,Morris SM Jr,Gause WC,Leibovich SJ,Haskó G.Adenosine promotes alternative macrophage activation via A2A andA2B receptors.FASEB J 2012;26(1):376–386.

140.Figler RA,Wang G,Srinivasan S,Jung DY,Zhang Z,Pankow JS,RavidK,Fredholm B,Hedrick CC,Rich SS,Kim JK,LaNoue KF,Linden J.Links between insulinresistance,adenosine A2B receptors,and inflammatory markers in mice andhumans.Diabetes 2011;60(2):669–679.

141.Ghaemi Oskouie F,Shameli A,Yang A,Desrosiers MD,Mucsi AD,BlackburnMR,Yang Y,Santamaria P,Shi Y.High levels of adenosine deaminase on dendriticcells promote autoreactive T cell activation and diabetes in nonobese diabeticmice.J Immunol 2011;186(12):6798–6806.

142.Rudich A,Tirosh A,Potashnik R,Hemi R,Kanety H,Bashan N. Prolongedoxidative stress impairs insulininduced GLUT4 translocation in 3T3-L1adipocytes.Diabetes 1998;47(10):1562–1569.

143.Maddux BA,See W,Lawrence JC Jr,Goldfine AL,Goldfine

ID,Evans JL.Protection against oxidative stressinduced

insulin resistance in rat L6 muscle cells by mircomolar

concentrations of alpha-lipoic acid.Diabetes 2001;50(2):

404–410.

144.Furukawa S,Fujita T,Shimabukuro M,Iwaki M,Yamada Y,

Nakajima Y,Nakayama O,Makishima M,Matsuda M,Shimomura I.Increased oxidativestress in obesity and its impact on metabolic syndrome.J Clin Invest2004;114(12):1752–1761.

145.Meigs JB,Larson MG,Fox CS,Keaney JF Jr,Vasan RS,Benjamin EJ.Associationof oxidative stress,insulin

resistance,and diabetes risk phenotypes:the Framingham

Offspring Study.Diabetes Care 2007;30(10):2529–2535.

146.Maritim AC,Sanders RA,Watkins JB 3rd.Diabetes,

oxidative stress, and antioxidants:a review.J Biochem MolToxicol2003;17(1):24–38.

147.Rauscher FM,Sanders RA,Watkins JB 3rd.Effects of

coenzyme Q10 treatment on antioxidant pathways in normal andstreptozotocin-induced diabetic rats.J Biochem Mol Toxicol 2001;15(1):41–46.

148.Candlish JK,Das NP.Antioxidants in food and chronic

degenerative diseases.Biomed Environ Sci 1996;9(2–3):

117–123.

149.Sanders RA,Rauscher FM,Watkins JB 3rd.Effects of

quercetin on antioxidant defense in streptozotocin-induced diabetic rats.JBiochem Mol Toxicol 2001;15(3):143–149.

150.KulczyńskiB,Sidor A,Gramza-Michałowska A.Characteristics ofselected antioxidative and bioactive compounds in meat and animal originproducts. Antioxidants (Basel)2019;8(9):335.

151.Obrosova IG,Stevens MJ.Effect of dietary taurine supplementation on GSHand NADP-redox status,lipid peroxidation,and energy metabolism in diabeticprecataractous lens.Invest Ophthalmol Vis Sci 1999; 40(3):680–688.

152.Aalto TK,Raivio KO.Mechanisms of adenine nucleotide

depletion from endothelial cells exposed to reactive oxygenmetabolites.Free Radic Biol Med 1993;14(2):177–183.

153.Aalto TK,Raivio KO.Adenine nucleotide depletion from

endothelial cells exposed to xanthine oxidase.Am J Physiol

1990;259(6 Pt 1):C883–C888.

154.Gerasimovskaya EV,Ahmad S,White CW,Jones PL,Carpenter TC, StenmarkKR.Extracellular ATP is an autocrine/paracrine regulator of hypoxia-inducedadventitial fibroblast growth.Signaling through extracellular signalregulatedkinase-1/2 and the Egr-1 transcription factor.J Biol Chem 2002;277(47):44638–44650.

155.Gerasimovskaya EV,Davie NJ,Ahmad S,Tucker DA,White CW,StenmarkKR.Extracellular adenosine triphosphate:a potential regulator of vasa vasorumneovascularization in hypoxia-induced pulmonary vascular remodeling.Chest2005;128(6 Suppl):608s–610s.

156.Piro S,Rabuazzo AM,Renis M,Purrello F.Effects of

metformin on oxidative stress, adenine nucleotides balance, andglucose-induced insulin release impaired by chronic

free fatty acids exposure in rat pancreatic islets.J Endocrinol Invest2012;35(5):504–510.

157.McCowen KC,Malhotra A,Bistrian BR.Stress-induced

hyperglycemia.Crit Care Clin 2001;17(1):107–124.

158.Bellodi G,Manicardi V,Malavasi V,Veneri L,Bernini G, BossiniP,Distefano S,Magnanini G,Muratori L,Rossi G, Zuarini A.Hyperglycemia andprognosis of acute myocardial

infarction in patients without diabetes mellitus.Am J Cardiol1989;64(14):885–888.

159.Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress

hyperglycaemia and increased risk of death after myocardial infarction inpatients with and without diabetes: a systematic overview.Lancet2000;355(9206):773–778.

160.Kosiborod M,Rathore SS,Inzucchi SE,Masoudi FA,Wang Y, HavranekEP,Krumholz HM.Admission glucose and mortality in elderly patients hospitalizedwith acute myocardial infarction:implications for patients with and withoutrecognized diabetes. Circulation 2005;111(23):3078–3086.

161.Capes SE,Hunt D,Malmberg K,Pathak P,Gerstein HC. Stress hyperglycemiaand prognosis of stroke in nondiabetic and diabetic patients:a systematicoverview.Stroke 2001;32(10):2426–2432.

162.Bruno A, Levine SR,Frankel MR, Brott TG,Lin Y,Tilley

BC, Lyden PD,Broderick JP,Kwiatkowski TG,Fineberg SE.Admission glucoselevel and clinical outcomes in the

NINDS rt-PA Stroke Trial.Neurology 2002;59(5):669–674.

163.Yendamuri S,Fulda GJ,Tinkoff GH.Admission hyperglycemia as a prognosticindicator in trauma.J Trauma 2003;55(1):33–38.

164.Sung J,Bochicchio GV,Joshi M,Bochicchio K,Tracy K, Scalea TM.Admissionhyperglycemia is predictive of outcome in critically ill trauma patients.JTrauma 2005;59(1):80–83.

165.Laird AM,Miller PR,Kilgo PD,Meredith JW,Chang MC. Relationship of earlyhyperglycemia to mortality in trauma

patients. J Trauma 2004;56(5):1058–1062.

166.Fredholm BB.Adenosine,an endogenous distress signal, modulates tissuedamage and repair.Cell Death Differ 2007;14(7):1315–1323.

167.Cekic C,Linden J.Purinergic regulation of the immune

system.Nat Rev Immunol 2016;16(3):177–192.

168.Pernicova I,Korbonits M.Metformin--mode of action and

clinical implications for diabetes and cancer.Nat Rev

Endocrinol 2014;10(3):143–156.

169.Foretz M,Guigas B,Viollet B.Understanding the glucoregulatorymechanisms of metformin in type 2 diabetes mellitus.Nat Rev Endocrinol2019;15(10):569–589.

170.Zhang CS,Li M,Ma T,Zong Y,Cui J,Feng JW,Wu YQ,Lin SY, Lin SC.Metforminactivates AMPK through the Lysosomal Pathway.Cell Metab 2016;24(4):521–522.

171.Hunter RW,Hughey CC,Lantier L,Sundelin EI,Peggie M, Zeqiraj E,SicheriF,Jessen N,Wasserman DH,Sakamoto K.Metformin reduces liver glucose productionby inhibition of fructose-1-6-bisphosphatase.Nat Med 2018;24(9):1395–1406.

172.Kolterman OG,Olefsky JM.The impact of sulfonylurea

treatment upon the mechanisms responsible for the insulin

resistance in type II diabetes. Diabetes Care 1984;7 Suppl 1:81–88.

173.Simonson DC,Ferrannini E,Bevilacqua S,Smith D, Barrett E,CarlsonR,DeFronzo RA.Mechanism of improvement in glucose metabolism after chronic glyburidetherapy.Diabetes 1984;33(9):838–845.

174.Pfeifer MA,Halter JB,Graf R,Porte D Jr.Potentiation of

insulin secretion to nonglucose stimuli in normal man by

tolbutamide.Diabetes 1980;29(5):335–340.

175.Groop L,Groop PH,Stenman S,Saloranta C,Tötterman

KJ,Fyhrquist F,Melander A.Comparison of pharmacokinetics,metabolic effectsand mechanisms of action of glyburide and glipizide during long-termtreatment.Diabetes Care 1987;10(6):671–678.

176.Boyd AE 3rd.Sulfonylurea receptors,ion channels,and

fruit flies.Diabetes 1988;37(7):847–850.

177.Eliasson L,Renström E,Ammälä C,Berggren PO, Bertorello AM,BokvistK,Chibalin A,Deeney JT,Flatt PR,Gäbel J,Gromada J,Larsson O,Lindström P,RhodesCJ, Rorsman P.PKC-dependent stimulation of exocytosis by sulfonylureas inpancreatic beta cells.Science 1996; 271(5250):813–815.

178.Sheppard DN,Welsh MJ.Inhibition of the cystic fibrosis

transmembrane conductance regulator by ATP-sensitive K+

channel regulators.Ann N Y Acad Sci 1993;707:275–284.

179.Hisadome K,Koyama T,Kimura C,Droogmans G,Ito Y,Oike M.Volume-regulatedanion channels serve as an auto/

paracrine nucleotide release pathway in aortic endothelial

cells.J Gen Physiol 2002;119(6):511–520.

180.Gallwitz B.Clinical use of DPP-4 inhibitors.Front Endocrinol (Lausanne)2019;10:389.

181.Gorrell MD,Gysbers V,McCaughan GW.CD26:a multifunctional integralmembrane and secreted protein of activated lymphocytes.Scand J Immunol2001;54(3):249–264.

182.ÖztürkB,Gürbüz AS,Durak ZE,Öztürk HS.Dipeptidyl

peptidase-4 and adenosine deaminase enzyme levels in

polycystic ovary syndrome.Gynecol Endocrinol 2019; 35(2):138–141.

183.Kather H.Pathways of purine metabolism in human adipocytes.Furtherevidence against a role of adenosine as an endogenous regulator of human fatcell function.J Biol Chem 1990;265(1):96–102.

184.Lee TM,Chen WT,Yang CC,Lin SZ,Chang NC.Sitagliptin attenuatessympathetic innervation via modulating reactive oxygen species and interstitialadenosine in

infarcted rat hearts.J Cell Mol Med 2015;19(2):418–429.