Skip to main content
Log in

From diabetes to renal aging: the therapeutic potential of adiponectin

  • Review
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Nowadays, the complications related to diabetes, such as nephropathy, cardiovascular problems, and aging, are highly being considered. Renal cell aging is affected by various mechanisms of inflammation, oxidative stress, and basement membrane thickening, which are significant causes of renal dysfunction in diabetes. Due to recent studies, adiponectin plays a key role in diabetes-related kidney diseases as a fat-derived hormone. In diabetes, reduced adiponectin levels are associated to renal cell aging. Oxidative stress and related signaling pathways are the main routes in which adiponectin may be effective to decline diabetes-associated aging. Therefore, adiponectin signaling in target tissues becomes one of the research areas of interest in metabolism and clinical medicine. Studies on adiponectin signaling will increase our understanding of adiponectin role in diabetes-linked diseases as well as shortening life span conditions which may guide the design of antidiabetic and anti-aging drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Abharzanjani F, Afshar M, Hemmati M, Moossavi M (2017) Short-term High Dose of Quercetin and Resveratrol Alters Aging Markers in Human Kidney Cells. Int J Prev Med 8:64. https://doi.org/10.4103/ijpvm.IJPVM_139_17

    Article  PubMed  PubMed Central  Google Scholar 

  2. Aimé C, André J-B, Raymond M (2017) Grandmothering and cognitive resources are required for the emergence of menopause and extensive post-reproductive lifespan. PLoS Comput Biol 13(7):e1005631. https://doi.org/10.1371/journal.pcbi.1005631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Amed S, Oram R (2016) Maturity-Onset Diabetes of the Young (MODY): Making the Right Diagnosis to Optimize Treatment. Can J Diabetes 40(5):449–454. https://doi.org/10.1016/j.jcjd.2016.03.002

    Article  PubMed  Google Scholar 

  4. American Diabetes Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Supplement 1):S67–S74. https://doi.org/10.2337/dc13-S067

    Article  Google Scholar 

  5. Awazawa M, Ueki K, Inabe K, Yamauchi T, Kubota N, Kaneko K, Kobayashi M, Iwane A, Sasako T, Okazaki Y, Ohsugi M (2011) Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway. Cell Metab 13(4):401–412. https://doi.org/10.1016/j.cmet.2011.02.010

    Article  CAS  PubMed  Google Scholar 

  6. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495. https://doi.org/10.1016/j.cell.2005.02.001

    Article  CAS  PubMed  Google Scholar 

  7. Bauer S, Weigert J, Neumeier M, Wanninger J, Schäffler A, Luchner A, Schnitzbauer AA, Aslanidis C, Buechler C (2010) Low-abundant adiponectin receptors in visceral adipose tissue of humans and rats are further reduced in diabetic animals. Arch Med Res 41(2):75–82. https://doi.org/10.1016/j.arcmed.2010.02.010

    Article  CAS  PubMed  Google Scholar 

  8. Bo J, Xie S, Guo Y, Zhang C, Guan Y, Li C, Lu J, Meng QH (2016) Methylglyoxal impairs insulin secretion of pancreatic β-cells through increased production of ROS and mitochondrial dysfunction mediated by upregulation of UCP2 and MAPKs. J Diabetes Res 2016:2029854. https://doi.org/10.1155/2016/2029854

    Article  CAS  PubMed  Google Scholar 

  9. Bobulescu IA (2010) Renal lipid metabolism and lipotoxicity. Curr Opin Nephrol Hypertens 19(4):393–402. https://doi.org/10.1097/MNH.0b013e32833aa4ac

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414(6865):813–820. https://doi.org/10.1038/414813a

    Article  CAS  PubMed  Google Scholar 

  11. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625. https://doi.org/10.2337/diabetes.54.6.1615

    Article  CAS  PubMed  Google Scholar 

  12. Cai W, He JC, Zhu L, Chen X, Wallenstein S, Striker GE, Vlassara H (2007) Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression. Am J Pathol 170(6):1893–1902. https://doi.org/10.2353/ajpath.2007.061281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chandrasekaran A, Idelchik MdPS, Melendez JA (2017) Redox control of senescence and age-related disease. Redox Biol 11:91–102. https://doi.org/10.1016/j.redox.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  14. Choi SR, Lim JH, Kim MY, Kim EN, Kim Y, Choi BS, Kim YS, Kim HW, Lim KM, Kim MJ, Park CW (2018) Adiponectin receptor agonist AdipoRon decreased ceramide, and lipotoxicity, and ameliorated diabetic nephropathy. Metabolism 85:348–360. https://doi.org/10.1016/j.metabol.2018.02.004

  15. Civitarese AE, Jenkinson CP, Richardson D, Bajaj M, Cusi K, Kashyap S, Berria R, Belfort R, DeFronzo RA, Mandarino LJ, Ravussin E (2004) Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes. Diabetologia 47(5):816–820. https://doi.org/10.1007/s00125-004-1359-x

    Article  CAS  PubMed  Google Scholar 

  16. Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L (2001) Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 108(12):1875–1881. https://doi.org/10.1172/JCI14120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Combs TP, Pajvani UB, Berg AH, Lin Y, Jelicks LA, Laplante M, Nawrocki AR, Rajala MW, Parlow AF, Cheeseboro L, Ding YY (2004) A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology 145(1):367–383. https://doi.org/10.1210/en.2003-1068

    Article  CAS  PubMed  Google Scholar 

  18. Daffu G, del Pozo CH, O'Shea KM, Ananthakrishnan R, Ramasamy R, Schmidt AM (2013) Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases and beyond. Int J Mol Sci 14(10):19891–19910. https://doi.org/10.3390/ijms141019891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. de Courten B, de Courten MP, Soldatos G, Dougherty SL, Straznicky N, Schlaich M, Sourris KC, Chand V, Scheijen JL, Kingwell BA, Cooper ME (2016) Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial. Am J Clin Nutr 103(6):1426–1433. https://doi.org/10.3945/ajcn.115.125427

    Article  CAS  PubMed  Google Scholar 

  20. De la Fuente M, Miquel J (2009) An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des 15(26):3003–3026. https://doi.org/10.2174/138161209789058110

    Article  PubMed  Google Scholar 

  21. de Bandeira MS, da Fonseca LJ, da Guedes SG, Rabelo LA, Goulart MO, Vasconcelos SM (2013) Oxidative stress as an underlying contributor in the development of chronic complications in diabetes mellitus. Int J Mol Sci 14(2):3265–3284. https://doi.org/10.3390/ijms14023265

    Article  CAS  PubMed Central  Google Scholar 

  22. Deepa SS, Dong LQ (2009) APPL1: role in adiponectin signaling and beyond. Am J Physiol Endocrinol Metab 296(1):E22–E36. https://doi.org/10.1152/ajpendo

    Article  CAS  PubMed  Google Scholar 

  23. Diamant M, Tushuizen ME (2006) The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD. Curr Diab Rep 6(4):279–286. https://doi.org/10.1007/s11892-006-0061-4

    Article  CAS  PubMed  Google Scholar 

  24. Dietze-Schroeder D, Sell H, Uhlig M, Koenen M, Eckel J (2005) Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors. Diabetes 54(7):2003–2011. https://doi.org/10.2337/diabetes.54.7.2003

    Article  CAS  PubMed  Google Scholar 

  25. Esmaeili S, Motamedrad M, Hemmati M, Mehrpour O, Khorashadizadeh M (2019) Prevention of kidney cell damage in hyperglycaemia condition by adiponectin. Cell Biochem Funct 37(3):148–152. https://doi.org/10.1002/cbf.3380

    Article  CAS  PubMed  Google Scholar 

  26. Fang F, Liu GC, Kim C, Yassa R, Zhou J, Scholey JW (2013) Adiponectin attenuates angiotensin II-induced oxidative stress in renal tubular cells through AMPK and cAMP-Epac signal transduction pathways. Am J Physiol Renal Physiol 304(11):F1366–F1374. https://doi.org/10.1152/ajprenal.00137.2012

  27. Fiaschi T, Buricchi F, Cozzi G, Matthias S, Parri M, Raugei G, Ramponi G, Chiarugi P (2007) Redox‐dependent and ligand‐independent trans‐activation of insulin receptor by globular adiponectin. Hepatology 46(1):130–139. https://doi.org/10.1002/hep.21643

  28. Frankenberg ADv, Reis AF, Gerchman F (2017) Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review. Arch Endocrinol Metab 61(6):614-622. https://doi.org/10.1590/2359-3997000000316

  29. Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, Knight AR, Taylor EL, Oettrich J, Ruskovska T, Gasparovic AC (2015) Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal 23(14):1144–1170. https://doi.org/10.1089/ars.2015.6317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98(4):2005–2010. https://doi.org/10.1073/pnas.041591798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fujita K, Nishizawa H, Funahashi T, Shimomura I, Shimabukuro M (2006) Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J 70(11):1437–1442. https://doi.org/10.1253/circj.70.1437

    Article  CAS  PubMed  Google Scholar 

  32. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114(12):1752–1761. https://doi.org/10.1172/JCI21625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gholami M, Hemmati M, Taheri-Ghahfarokhi A, Hoshyar R, Moossavi M (2016) Expression of glucokinase, glucose 6-phosphatase, and stress protein in streptozotocin-induced diabetic rats treated with natural honey. Int J Diabetes Dev Ctries 36(1):125–131. https://doi.org/10.1007/s13410-015-0456-3

    Article  CAS  Google Scholar 

  34. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070. https://doi.org/10.1161/CIRCRESAHA.110.223545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Golbidi S, Ebadi SA, Laher I (2011) Antioxidants in the treatment of diabetes. Curr Diabetes Rev 7(2):106–125. https://doi.org/10.2174/157339911794940729

    Article  CAS  PubMed  Google Scholar 

  36. Gray JP, Heart E (2010) Usurping the mitochondrial supremacy: extramitochondrial sources of reactive oxygen intermediates and their role in beta cell metabolism and insulin secretion. Toxicol Mech Methods 20(4):167–174. https://doi.org/10.3109/15376511003695181

    Article  CAS  PubMed  Google Scholar 

  37. Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El-Osta A, Andrews KL, Chin-Dusting JP, Touyz RM, Wingler K, Cooper ME, Schmidt HH, Jandeleit-Dahm KA (2013) NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127(18):1888–1902. https://doi.org/10.1161/CIRCULATIONAHA.112.132159

    Article  CAS  PubMed  Google Scholar 

  38. Gray SP, Jha JC, Kennedy K, Van Bommel E, Chew P, Szyndralewiez C, Touyz RM, Schmidt HH, Cooper ME, Jandeleit-Dahm KA (2017) Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease. Diabetologia 60(5):927–937. https://doi.org/10.1007/s00125-017-4215-5

    Article  CAS  PubMed  Google Scholar 

  39. Gu W, Li X, Liu C, Yang J, Ye L, Tang J, Gu Y, Yang Y, Hong J, Zhang Y, Chen M (2006) Globular adiponectin augments insulin secretion from pancreatic islet β cells at high glucose concentrations. Endocrine 30(2):217–221. https://doi.org/10.1385/ENDO:30:2:217

    Article  CAS  PubMed  Google Scholar 

  40. Guan SS, Sheu ML, Yang RS, Chan DC, Wu CT, Yang TH, Chiang CK, Liu SH (2016) The pathological role of advanced glycation end products-downregulated heat shock protein 60 in islet β-cell hypertrophy and dysfunction. Oncotarget 7(17):23072–23087. https://doi.org/10.18632/oncotarget.8604

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hanssen NM, Beulens JW, Van Dieren S, Scheijen JL, Spijkerman AM, van der Schouw YT, Stehouwer CD, Schalkwijk CG (2015) Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes 64(1):257–265. https://doi.org/10.2337/db13-1864

    Article  CAS  PubMed  Google Scholar 

  42. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300. https://doi.org/10.1093/geronj/11.3.298

    Article  CAS  PubMed  Google Scholar 

  43. Hemmati M, Asghari S, Zohoori E (2015) Effects of alcoholic and aqueous extract of barberry, jujube and saffron petals on serum level of adiponectin and lipid profile in diabetic rats. IJEM 16(5):329–337 [In Persian]

    Google Scholar 

  44. Hemmati M, Mahboob Z (2016) Diabetic retinopathy: its mechanism and therapeutic strategies. IJEM 17(6):477–488 [In Persian]

  45. Hemmati M, Zohoori E, Mehrpour O, Karamian M, Asghari S, Zarban A, Nasouti R (2015) Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions. EXCLI J 14:908–915. https://doi.org/10.17179/excli2015-232

  46. Hutchinson KR, Lord CK, West TA, Stewart JA Jr (2013) Cardiac fibroblast-dependent extracellular matrix accumulation is associated with diastolic stiffness in type 2 diabetes. PLoS One 8(8):e72080. https://doi.org/10.1371/journal.pone.0072080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Iwabu M, Okada-Iwabu M, Yamauchi T, Kadowaki T (2015) Adiponectin/adiponectin receptor in disease and aging. NPJ Aging Mech Dis 1:15013. https://doi.org/10.1038/npjamd.2015.13

    Article  PubMed  PubMed Central  Google Scholar 

  48. Johnson RC, Leopold JA, Loscalzo J (2006) Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res 99(10):1044–1059. https://doi.org/10.1161/01.RES.0000249379.55535.21

    Article  CAS  PubMed  Google Scholar 

  49. Kadowaki T, Yamauchi T, Kubota N (2008) The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett 582(1):74–80. https://doi.org/10.1016/j.febslet.2007.11.070

    Article  CAS  PubMed  Google Scholar 

  50. Kharroubi I, Rasschaert J, Eizirik DL, Cnop M (2003) Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun 312(4):1118–1122. https://doi.org/10.1016/j.bbrc.2003.11.042

    Article  CAS  PubMed  Google Scholar 

  51. Kim Y, Lim JH, Kim MY, Kim EN, Yoon HE, Shin SJ, Choi BS, Kim YS, Chang YS, Park CW (2018) The adiponectin receptor agonist AdipoRon ameliorates diabetic nephropathy in a model of type 2 diabetes. J Am Soc Nephrol 29(4):1108–1127. https://doi.org/10.1681/ASN.2017060627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kobayashi H, Otsuka H, Yanai M, Haketa A, Hara M, Hishiki M, Abe M, Soma M (2018) Adiponectin is not associated with renal function decline in community-dwelling elderly adults. Medicine (Baltimore) 97(21):e10847. https://doi.org/10.1097/MD.0000000000010847

    Article  CAS  Google Scholar 

  53. Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim MS, Kim SW, Park IS, Youn JH (2007) Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes 56(12):2973–2981. https://doi.org/10.2337/db07-0510

    Article  CAS  PubMed  Google Scholar 

  54. Koulis C, Watson A, Gray S, Jandeleit-Dahm K (2015) Linking RAGE and Nox in diabetic micro- and macrovascular complications. Diabetes Metab 41(4):272–281. https://doi.org/10.1016/j.diabet.2015.01.006

    Article  CAS  PubMed  Google Scholar 

  55. Lassègue B, San Martín A, Griendling KK (2012) Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110(10):1364–1390. https://doi.org/10.1161/CIRCRESAHA.111.243972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lenaz G (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52(3-5):159–164. https://doi.org/10.1080/15216540152845957

    Article  CAS  PubMed  Google Scholar 

  57. Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, Lopez BL, Tao L, Goldstein BJ, Gao F, Ma XL (2007) Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity. Am J Physiol Endocrinol Metab 293(6):E1703–E1708. https://doi.org/10.1152/ajpendo.00462.2007

    Article  CAS  PubMed  Google Scholar 

  58. Ma K, Cabrero A, Saha PK, Kojima H, Li L, Chang BH, Paul A, Chan L (2002) Increased β-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem 277(38):34658–34661. https://doi.org/10.1074/jbc.C200362200

    Article  CAS  PubMed  Google Scholar 

  59. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221(2):286–289. https://doi.org/10.1006/bbrc.1996.0587

    Article  CAS  PubMed  Google Scholar 

  60. Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney V, Friedman EA, Cerami A, Vlassara H (1991) Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 325(12):836–842. https://doi.org/10.1056/NEJM199109193251202

    Article  CAS  PubMed  Google Scholar 

  61. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mao X, Kikani CK, Riojas RA, Langlais P, Wang L, Ramos FJ, Fang Q, Christ-Roberts CY, Hong JY, Kim RY, Liu F (2006) APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol 8(5):516–523. https://doi.org/10.1038/ncb1404

    Article  CAS  PubMed  Google Scholar 

  63. Matsuda M, Shimomura I (2014) Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord 15(1):1–10. https://doi.org/10.1007/s11154-013-9271-7

    Article  CAS  PubMed  Google Scholar 

  64. Monnier VM (1989) Toward a Maillard reaction theory of aging. Prog Clin Biol Res 304:1–22

    CAS  PubMed  Google Scholar 

  65. Moschen AR, Wieser V, Tilg H (2012) Adiponectin: key player in the adipose tissue-liver crosstalk. Curr Med Chem 19(32):5467–5473. https://doi.org/10.2174/092986712803833254

    Article  CAS  PubMed  Google Scholar 

  66. Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L (2006) Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor γ agonists. J Biol Chem 281(5):2654–2660. https://doi.org/10.1074/jbc.M505311200

    Article  CAS  PubMed  Google Scholar 

  67. NCD Risk Factor Collaboration (NCD-RisC) (2016) Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387(10027):1513–1530. https://doi.org/10.1016/S0140-6736(16)00618-8

    Article  Google Scholar 

  68. Nowotny K, Jung T, Höhn A, Weber D, Grune T (2015) Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules 5(1):194–222. https://doi.org/10.3390/biom5010194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Okamoto M, Ohara-Imaizumi M, Kubota N, Hashimoto S, Eto K, Kanno T, Kubota T, Wakui M, Nagai R, Noda M, Nagamatsu S (2008) Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration. Diabetologia 51(5):827–835. https://doi.org/10.1007/s00125-008-0944-9

    Article  CAS  PubMed  Google Scholar 

  70. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N (2002) Adiponectin reduces atherosclerosis in apolipoprotein Edeficient mice. Circulation 106(22):2767–2770. https://doi.org/10.1161/01.cir.0000042707.50032.19

    Article  CAS  PubMed  Google Scholar 

  71. Ott C, Jacobs K, Haucke E, Santos AN, Grune T, Simm A (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429. https://doi.org/10.1016/j.redox.2013.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87(1):315–424. https://doi.org/10.1152/physrev.00029.2006

    Article  CAS  PubMed  Google Scholar 

  73. Panten U, Klein H (1982) O2 consumption by isolated pancreatic islets, as measured in a microincubation system with a Clark-type electrode. Endocrinology 111(5):1595–1600. https://doi.org/10.1210/endo-111-5-1595

    Article  CAS  PubMed  Google Scholar 

  74. Pickering RJ, Rosado CJ, Sharma A, Buksh S, Tate M, de Haan JB (2018) Recent novel approaches to limit oxidative stress and inflammation in diabetic complications. Clin Transl Immunology 7(4):e1016. https://doi.org/10.1002/cti2.1016

    Article  PubMed  PubMed Central  Google Scholar 

  75. Rehman K, Akash MSH (2017) Mechanism of generation of oxidative stress and pathophysiology of Type 2 diabetes mellitus: how are they interlinked? J Cell Biochem 118(11):3577–3585. https://doi.org/10.1002/jcb.26097

  76. Reynaert NL, Gopal P, Rutten EP, Wouters EF, Schalkwijk CG (2016) Advanced glycation end products and their receptor in age-related, non-communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease. Int J Biochem Cell Biol 81(Pt B):403–418. https://doi.org/10.1016/j.biocel.2016.06.016

    Article  CAS  PubMed  Google Scholar 

  77. Rutter GA, Pullen TJ, Hodson DJ, Martinez-Sanchez A (2015) Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem J 466(2):203–218. https://doi.org/10.1042/BJ20141384

    Article  CAS  PubMed  Google Scholar 

  78. Salisbury D, Bronas U (2015) Reactive oxygen and nitrogen species: impact on endothelial dysfunction. Nurs Res 64(1):53–66. https://doi.org/10.1097/NNR.0000000000000068

    Article  PubMed  Google Scholar 

  79. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes.J. Biol Chem 270(45):26746–26749. https://doi.org/10.1074/jbc.270.45.26746

    Article  CAS  Google Scholar 

  80. Schuit F, De Vos A, Farfari S, Moens K, Pipeleers D, Brun T, Prentki M (1997) Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem 272(30):18572–18579. https://doi.org/10.1074/jbc.272.30.18572

    Article  CAS  PubMed  Google Scholar 

  81. Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, Girotti M, Marie S, MacDonald MJ, Wollheim CB (1994) Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem 269(7):4895–4902

    Article  CAS  PubMed  Google Scholar 

  82. Shapiro L, Scherer PE (1998) The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 8(6):335–338. https://doi.org/10.1016/s0960-9822(98)70133-2

    Article  CAS  PubMed  Google Scholar 

  83. Singh VP, Bali A, Singh N, Jaggi AS (2014) Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 18(1):1–14. https://doi.org/10.4196/kjpp.2014.18.1.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Soman S, Raju R, Sandhya VK, Advani J, Khan AA, Harsha HC, Prasad TS, Sudhakaran PR, Pandey A, Adishesha PK (2013) A multicellular signal transduction network of AGE/RAGE signaling. J Cell Commun Signal 7(1):19–23. https://doi.org/10.1007/s12079-012-0181-3

    Article  PubMed  Google Scholar 

  85. Sowers JR (2008) Endocrine functions of adipose tissue: focus on adiponectin. Clin Cornerstone 9(1):32–38. https://doi.org/10.1016/s1098-3597(08)60026-5

    Article  PubMed  Google Scholar 

  86. Staiger K, Stefan N, Staiger H, Brendel MD, Brandhorst D, Bretzel RG, Machicao F, Kellerer M, Stumvoll M, Fritsche A, Häring HU (2005) Adiponectin is functionally active in human islets but does not affect insulin secretory function or β-cell lipoapoptosis. J Clin Endocrinol Metab 90(12):6707-6713. https://doi.org/10.1210/jc.2005-0467

  87. Stitt AW, Li YM, Gardiner TA, Bucala R, Archer DB, Vlassara H (1997) Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats. Am J Pathol 50(2):523–531

    Google Scholar 

  88. Stitt AW, Moore JE, Sharkey JA, Murphy G, Simpson DA, Bucala R, Vlassara H, Archer DB (1998) Advanced glycation end products in vitreous: Structural and functional implications for diabetic vitreopathy. Invest Ophthalmol Vis Sci 39(13):2517–2523

    CAS  PubMed  Google Scholar 

  89. Sukumar P, Viswambharan H, Imrie H, Cubbon RM, Yuldasheva N, Gage M, Galloway S, Skromna A, Kandavelu P, Santos CX, Gatenby VK, Smith J, Beech DJ, Wheatcroft SB, Channon KM, Shah AM, Kearney MT (2013) Nox2 NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction. Diabetes 62(6):2130–2134. https://doi.org/10.2337/db12-1294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Tahara N, Yamagishi S, Matsui T, Takeuchi M, Nitta Y, Kodama N, Mizoguchi M, Imaizumi T (2012) Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in nondiabetic subjects. Cardiovasc Ther 30(1):42–48. https://doi.org/10.1111/j.1755-5922.2010.00177.x

    Article  CAS  PubMed  Google Scholar 

  91. Takeda Y, Nakanishi K, Tachibana I, Kumanogoh A (2012) Adiponectin: a novel link between adipocytes and COPD. Vitam Horm 90:419–435. https://doi.org/10.1016/B978-0-12-398313-8.00016-6

    Article  CAS  PubMed  Google Scholar 

  92. Tan KC, Xu A, Chow WS, Lam MC, Ai VH, Tam SC, Lam KS (2004) Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 89(2):765–769. https://doi.org/10.1210/jc.2003-031012

    Article  CAS  PubMed  Google Scholar 

  93. Tan KC, Shiu SW, Wong Y, Tam X (2011) Serum advanced glycation end products (AGEs) are associated with insulin resistance. Diabetes Metab Res Rev 27(5):488–492. https://doi.org/10.1002/dmrr.1188

    Article  CAS  PubMed  Google Scholar 

  94. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, Lopez BL, Koch W, Chan L, Goldstein BJ, Ma XL (2007) Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115(11):1408–1416. https://doi.org/10.1161/CIRCULATIONAHA.106.666941

    Article  CAS  PubMed  Google Scholar 

  95. Tarasov AI, Semplici F, Li D, Rizzuto R, Ravier MA, Gilon P, Rutter GA (2013) Frequency-dependent mitochondrial Ca 2+ accumulation regulates ATP synthesis in pancreatic β cells. Pflügers Arch 465(4):543–554. https://doi.org/10.1007/s00424-012-1177-9

  96. Tian M, Tang L, Wu Y, Beddhu S, Huang Y (2018) Adiponectin attenuates kidney injury and fibrosis in deoxycorticosterone acetate-salt and angiotensin II-induced CKD mice. Am J Physiol Renal Physiol 315(3):F558–F571. https://doi.org/10.1152/ajprenal.00137.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R, UK Prospective Diabetes Study (UKPDS) Group (1997) UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet 350(9087):1288–1293. https://doi.org/10.1016/s0140-6736(97)03062-6

    Article  CAS  PubMed  Google Scholar 

  98. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N (2004) Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 279(29):30817–30822. https://doi.org/10.1074/jbc.M402367200

    Article  CAS  PubMed  Google Scholar 

  99. Vlassara H, Uribarri J (2014) Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Curr Diab Rep 14(1):453. https://doi.org/10.1007/s11892-013-0453-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Volpe CMO, Villar-Delfino PH, dos Anjos PMF, Nogueira-Machado JA (2018) Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 25;9(2):119. https://doi.org/10.1038/s41419-017-0135-z

    Article  CAS  Google Scholar 

  101. Wang C, Mao X, Wang L, Liu M, Wetzel MD, Guan KL, Dong LQ, Liu F (2007) Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J Biol Chem 282(11):7991–7996. https://doi.org/10.1074/jbc.M700098200

    Article  CAS  PubMed  Google Scholar 

  102. Wang Y, Gao E, Tao L, Lau WB, Yuan Y, Goldstein BJ, Lopez BL, Christopher TA, Tian R, Koch W, Ma XL (2009) AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin. Circulation 119(6):835–844. https://doi.org/10.1161/CIRCULATIONAHA.108.815043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wendt T, Tanji N, Guo J, Hudson BI, Bierhaus A, Ramasamy R, Arnold B, Nawroth PP, Yan SF, D'Agati V, Schmidt AM (2003) Glucose, glycation, and RAGE: implications for amplification of cellular dysfunction in diabetic nephropathy. J Am Soc Nephrol 14(5):1383–1395. https://doi.org/10.1097/01.asn.0000065100.17349.ca

    Article  CAS  PubMed  Google Scholar 

  104. Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB (2006) Adiponectin–a key adipokine in the metabolic syndrome. Diabetes Obes Metab 8(3):264–280. https://doi.org/10.1111/j.1463-1326.2005.00510.x

    Article  CAS  PubMed  Google Scholar 

  105. Winzell MS, Nogueiras R, Dieguez C, Ahrén B (2004) Dual action of adiponectin on insulin secretion in insulin-resistant mice. Biochem Biophys Res Commun 321(1):154–160. https://doi.org/10.1016/j.bbrc.2004.06.130

    Article  CAS  PubMed  Google Scholar 

  106. Xi W, Satoh H, Kase H, Suzuki K, Hattori Y (2005) Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced NO production: vasorelaxation in response to globular adiponectin. Biochem Biophys Res Commun 332(1):200–205. https://doi.org/10.1016/j.bbrc.2005.04.111

    Article  CAS  PubMed  Google Scholar 

  107. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423(6941):762–769. https://doi.org/10.1038/nature01705

    Article  CAS  PubMed  Google Scholar 

  108. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13(3):332–339. https://doi.org/10.1038/nm1557

    Article  CAS  PubMed  Google Scholar 

  109. Yan SF, Ramasamy R, Bucciarelli LG, Wendt T, Lee LK, Hudson BI, Stern DM, Lalla E, DU Yan S, Rong LL, Naka Y, Schmidt AM (2004) RAGE and its ligands: a lasting memory in diabetic complications? Diab Vasc Dis Res 1(1):10–20. https://doi.org/10.3132/dvdr.2004.001

    Article  PubMed  Google Scholar 

  110. Yi W, Sun Y, Gao E, Wei X, Lau WB, Zheng Q, Wang Y, Yuan Y, Wang X, Tao L, Li R (2011) Reduced cardioprotective action of adiponectin in high-fat diet–induced type II diabetic mice and its underlying mechanisms. Antioxid Redox Signal 15(7):1779–1788. https://doi.org/10.1089/ars.2010.3722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zuo Y (2018) The role of adiponectin gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes. Eur Rev Med Pharmacol Sci 22(4):1106–1112. https://doi.org/10.26355/eurrev_201802_14398

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

MK and MH make substantial contributions to conception and design. MK, MM, and MH participate in drafting the article or revising it critically for important intellectual content. All authors give final approval of the version to be submitted and any revised version.

Corresponding author

Correspondence to Mina Hemmati.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Key points

- Adiponectin improves insulin resistance through mTOR signaling

- Adiponectin improves lipotoxicity in renal cells

- Adiponectin alleviates renal cell aging

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karamian, M., Moossavi, M. & Hemmati, M. From diabetes to renal aging: the therapeutic potential of adiponectin. J Physiol Biochem 77, 205–214 (2021). https://doi.org/10.1007/s13105-021-00790-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-021-00790-4

Keywords

Navigation