Molecular and Cellular Biochemistry

, Volume 380, Issue 1–2, pp 73–81 | Cite as

Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes

  • Suleyman AydinEmail author
  • Tuncay Kuloglu
  • Suna Aydin
  • Mehmet Nesimi Eren
  • Musa Yilmaz
  • Mehmet Kalayci
  • İbrahim Sahin
  • Nevin Kocaman
  • Cihan Citil
  • Yalcin Kendir


We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate–citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.


Adropin expression Immunohistochemistry STZ-induced diabetes Rat tissues 


Conflict of interest

The authors have not disclosed any potential conflicts of interest.


  1. 1.
    Nicholson G, Hall GM (2011) Diabetes mellitus: new drugs for a new epidemic. Br J Anaesth 107:65–73PubMedCrossRefGoogle Scholar
  2. 2.
  3. 3.
    McNay EC, Teske JA, Kotz CM, Dunn-Meynell A, Levin BE, McCrimmon RJ, Sherwin RS (2013) Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy. Am J Physiol Endocrinol Metab 304:E131–E138PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Aydin S (2013) Role of NUCB2/nesfatin-1 as a possible biomarker. Curr Pharm Des. PMID: 23537082Google Scholar
  5. 5.
    Aydin S (2010) The presence of the peptides apelin, ghrelin and nesfatin–1 in the human breast milk, and the lowering of their levels in patients with gestational diabetes mellitus. Peptides 31:2236–2240PubMedCrossRefGoogle Scholar
  6. 6.
    Kuloglu T, Dabak DO (2009) Determination of ghrelin immunoreactivity in kidney tissues of diabetic rats. Ren Fail 31:562–566PubMedCrossRefGoogle Scholar
  7. 7.
    Yang M, Zhang Z, Wang C, Li K, Li S, Boden G, Li L, Yang G (2012) Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance. Diabetes 61:1959–1968PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Luo KR, Chao CC, Hsieh PC, Lue JH, Hsieh ST (2012) Effect of glycemic control on sudomotor denervation in type 2 diabetes. Diabetes Care 35:612–616PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Sokolovska J, Isajevs S, Sugoka O, Sharipova J, Paramonova N, Isajeva D, Rostoka E, Sjakste T, Kalvinsh I, Sjakste N (2012) Comparison of the effects of glibenclamide on metabolic parameters, GLUT1 expression, and liver injury in rats with severe and mild streptozotocin-induced diabetes mellitus. Medicina (Kaunas) 48:532–543Google Scholar
  10. 10.
    van de Ven KC, Tack CJ, Heerschap A, van der Graaf M, de Galan BE (2013) Patients with type 1 diabetes exhibit altered cerebral metabolism during hypoglycemia. J Clin Invest 123:623–629Google Scholar
  11. 11.
    Zhang L, Xiong XQ, Fan ZD, Gan XB, Ago XY, Zhu GQ (2012) Involvement of enhanced cardiac sympathetic afferent reflex in sympathetic activation in early stage of diabetes. J Appl Physiol 113:47–55PubMedCrossRefGoogle Scholar
  12. 12.
    Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA (2008) Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 8:468–481PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, Culler MD, Mynatt RL, Butler AA (2012) Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 20:1394–1402CrossRefGoogle Scholar
  14. 14.
    Celik E, Yilmaz E, Celik O, Ulas M, Turkcuoglu I, Karaer A, Celik ESimsek Y, Minareci Y, Aydin S (2013) Maternal and fetal adropin levels in gestational diabetes mellitus. J Perinat Med 1–6Google Scholar
  15. 15.
    Aydin S (2013) Presence of adropin, nesfatin–1, apelin–12, ghrelins and salusins peptides in the milk, cheese whey and plasma of dairy cows. Peptides 43:83–87Google Scholar
  16. 16.
    Hsu SM, Raine L, Fanger H (1981) Use of avidin–biotin–peroxidase complex (ABC) in immunoperoxidase technique. J Histochem Cytochem 29:577–580PubMedCrossRefGoogle Scholar
  17. 17.
    Aydin S, Ozercan IH, Geckil H, Dagli F, Aydin S, Kumru S, Kilic N, Sahin I, Ozercan MR (2007) Ghrelin is present in teeth. J Biochem Mol Biol 40:368–372PubMedCrossRefGoogle Scholar
  18. 18.
    Kuloglu T, Aydin S (2013) Immunohistochemical expressions of adropin and inducible nitric oxide synthase in the renal tissues of rats with streptozotocin-induced experimental diabetes. Biotech Histochem (Submitted)Google Scholar
  19. 19.
    Gutierrez JC, Bahamonde J, Prater MR, Yefi CP, Holladay SD (2010) Production of a type 2 maternal diabetes rodent model using the combination of high-fat diet and moderate dose of streptozocin. Endocr Res 35:59–70PubMedCrossRefGoogle Scholar
  20. 20.
    Celik A, Balin M, Kobat MA, Erdem K, Baydas A, Bulut M, Altas Y, Aydin S, Aydin S (2013) Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther 3:174–178Google Scholar
  21. 21.
    Aberg ND, Brywe KG, Isgaard J (2006) Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. Sci World J 6:53–80CrossRefGoogle Scholar
  22. 22.
    Liu X, Yao DL, Bondy CA, Brenner M, Hudson LD, Zhou J, Webster HD (1994) Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. Mol Cell Neurosci 5:418–430PubMedCrossRefGoogle Scholar
  23. 23.
    Aydin S, Dag E, Ozkan Y, Erman F, Dagli AF, Kilic N, Sahin I, Karatas F, Yoldas T, Barim AO, Kendir Y (2009) Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders. Mol Cell Biochem 328:49–56PubMedCrossRefGoogle Scholar
  24. 24.
    Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, Eguchi H, Yamamoto M, Imaki T, Hashimoto K, Tsuchiya T, Monden T, Horiguchi K, Yamada M, Mori M (2006) Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443:709–712PubMedCrossRefGoogle Scholar
  25. 25.
    O’Carroll AM, Selby TL, Palkovits M, Lolait SJ (2000) Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues. Biochim Biophys Acta 1492:72–80PubMedCrossRefGoogle Scholar
  26. 26.
    Dagli AF, Aydin S, Karaoglu A, Akpolat N, Ozercan IH, Ozercan MR (2009) Ghrelin expression in normal kidney tissue and renal carcinomas. Pathol Res Pract 205:165–173PubMedCrossRefGoogle Scholar
  27. 27.
    Day RT, Cavaglieri RC, Feliers D (2013) Apelin retards the progression of diabetic nephropathy. Am J Physiol Renal Physiol 6:53–80Google Scholar
  28. 28.
    Hus-Citharel A, Bouby N, Frugière A, Bodineau L, Gasc JM, Llorens-Cortes C (2008) Effect of apelin on glomerular hemodynamic function in the rat kidney. Kidney Int 74:486–494PubMedCrossRefGoogle Scholar
  29. 29.
    Sahin I, Aydin S (2012) Serum concentration and kidney expression of salusin-α and salusin-β in rats with metabolic syndrome induced by fructose. Biotech Histochem 88:153–160Google Scholar
  30. 30.
    Aydin S, Eren MN, Aydin S, Ozercan IH, Dagli AF (2012) The bioactive peptides salusins and apelin-36 are produced in human arterial and venous tissues and the changes of their levels during cardiopulmonary bypass. Peptides 37:233–239PubMedCrossRefGoogle Scholar
  31. 31.
    Kleinz MJ, Davenport AP (2004) Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 118:119–125PubMedCrossRefGoogle Scholar
  32. 32.
    Kleinz MJ, Skepper JN, Davenport AP (2005) Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Regul Pept 126:233–240PubMedCrossRefGoogle Scholar
  33. 33.
    Dezaki K, Yada T (2012) Islet β-cell ghrelin signaling for inhibition of insulin secretion. Methods Enzymol 514:317–331PubMedCrossRefGoogle Scholar
  34. 34.
    Dun SL, Brailoiu GC, Brailoiu E, Yang J, Chang JK, Dun NJ (2006) Distribution and biological activity of obestatin in the rat. J Endocrinol 191:481–489PubMedCrossRefGoogle Scholar
  35. 35.
    Grönberg M, Tsolakis AV, Magnusson L, Janson ET, Saras J (2008) Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. J Histochem Cytochem 56:793–801PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Drenckhahn D, Mannherz HG (1983) Distribution of actin and the actin-associated proteins myosin, tropomyosin, alpha-actinin, vinculin, and villin in rat and bovine exocrine glands. Eur J Cell Biol 30:167–176PubMedGoogle Scholar
  37. 37.
    Murakami K, Taniguchi H, Baba S (1982) Presence of insulin-like immunoreactivity and its biosynthesis in rat and human parotid gland. Diabetologia 22:358–361PubMedCrossRefGoogle Scholar
  38. 38.
    Murakami K, Taniguchi H, Tamagawa M, Ejiri K, Baba S (1982) Modulation of somatostatin release by endogenous glucagon and insulin: physiological relationship between A, B and D cells in rat pancreatic islets. Endocrinol Jpn 29:503–508PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Suleyman Aydin
    • 1
    • 7
    Email author
  • Tuncay Kuloglu
    • 2
  • Suna Aydin
    • 3
    • 4
  • Mehmet Nesimi Eren
    • 5
  • Musa Yilmaz
    • 1
  • Mehmet Kalayci
    • 1
  • İbrahim Sahin
    • 1
    • 6
  • Nevin Kocaman
    • 2
  • Cihan Citil
    • 1
  • Yalcin Kendir
    • 1
  1. 1.Department of Medical Biochemistry (Firat Hormone Research Groups)School of Medicine, Firat UniversityElazigTurkey
  2. 2.Department of Histology & EmbryologySchool of Medicine, Firat UniversityElazigTurkey
  3. 3.Department of AnatomySchool of Medicine, Firat UniversityElazigTurkey
  4. 4.Clinic of Cardiovascular Surgery, Elazig Research and Education HospitalElazigTurkey
  5. 5.Department of Cardiovascular SurgerySchool of Medicine, Dicle UniversityDiyarbakirTurkey
  6. 6.Department of Histology & EmbryologySchool of Medicine, Erzincan UniversityErzincanTurkey
  7. 7.Department of Medical Biochemistry and Clinical Biochemistry (Firat Hormones Research Group)Medical School, Firat UniversityElazigTurkey

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