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The Effect of Zinc supplementation on Ghrelin-Immunoreactive Cells and Lipid Parameters in Gastrointestinal Tissue of Streptozotocin-Induced Female Diabetic Rats

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Abstract

Zinc is an essential nutrient with a wide range of functions and closely involved in a variety of enzymatic processes of importance in glucose, protein and lipid metabolism. Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor. The regulatory mechanism that explain the biosynthesis and secretion of ghrelin in the gastrointestinal tract has not been clarified. This study was undertaken to examine the effect of zinc supplementation on the streptozotocin (STZ)-induced diabetic rats, which exhibits ghrelin production and secretion, and lipid metabolism on the gastrointestinal tract. The animals were divided into four groups. Group I: Non-diabetic untreated animals. Group II: Zinc-treated non-diabetic rats. Group III: STZ-induced diabetic untreated animals. Group IV: Zinc-treated diabetic animals. Zinc sulfate was given to some of the experimental animals by gavage at a dose of 100 mg/kg body weight every day for 60 days. In the zinc-treated diabetic group, the blood glucose levels decreased and body weight increased as compared to the diabetic untreated group. Zinc supplementation to STZ-diabetic rats revealed the protective effect of zinc on lipids parameters such as total lipid, cholesterol, HDL-cholesterol and atherogenic index. There is no statistically change in ghrelin-immunoreactive cells in gastrointestinal tissue. But, it has found that zinc supplementation caused a significant reduction in densities of ghrelin-producing cells of fundic mucosa of zinc-treated diabetic animals as compared to untreated, non-diabetic controls. Zinc supplementation may contribute to prevent some complications of diabetic rats, biochemically.

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References

  1. Bray TM, Bettger WJ: The physiological role of zinc as an antioxidant. Free Radic Biol Med 8: 281–291, 1990

    Article  PubMed  CAS  Google Scholar 

  2. Powell SR: The antioxidant properties of zinc. J Nutr 130:1447–1454, 2000

    Google Scholar 

  3. Chausmer AB: Zinc, insulin and diabetes. J Am Coll Nutr 17:109–115, 1998

    PubMed  CAS  Google Scholar 

  4. Song MK, Rosenthal MJ, Hong S, Harris DM, Hwang I, Yip I, Golub MS, Ament ME, Go VL: Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid. Metabolism 50: 53–59, 2001

    Article  PubMed  CAS  Google Scholar 

  5. King JC, Shames DM, Woodhouse LR: Zinc homeostasis in humans. J Nutr 130: 1360–1366, 2000

    Google Scholar 

  6. Tapiero H, Tew KD: Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother 57: 399–411, 2003

    Article  PubMed  CAS  Google Scholar 

  7. Ghishan FK, Greene HL: Intestinal transport of zinc in the diabetic rat. Life Sci 32: 1735–1741, 1983

    Article  PubMed  CAS  Google Scholar 

  8. Kinlaw WB, Levine AS, Morley JE, Silvis SE, McClain CJ: Abnormal zinc metabolism in type II diabetes mellitus. Am J Med 75: 273–277, 1983

    Article  PubMed  CAS  Google Scholar 

  9. Terres-Martos C, Navarro-Alarcon M, Martin-Lagos F, Lopez G, de la Serrana H, Perez-Valero V, Lopez-Martinez MC: Serum zinc and copper concentrations and Cu/Zn ratios in patients with hepatopathies or diabetes. J Trace Elem Med Biol 2: 44–49, 1998

    Google Scholar 

  10. Lau AL, Failla ML: Urinary excretion of zinc, copper and iron in the streptozotocin- diabetic rat. J Nutr 114: 224–233, 1984

    PubMed  CAS  Google Scholar 

  11. Yoshikawa Y, Ueda E, Kojima Y, Sakurai H: The action mechanism of zinc (II) complexes with insulinomimetic activity in rat adipocytes. Life Sci 75: 741–751, 2004

    Article  PubMed  CAS  Google Scholar 

  12. Hiller R, Seigel D, Sperduto RD, Blair N, Burton TC, Farber MD, Gragoudas ES, Gunter EW, Haller J, Seddon JM : Serum zinc and serum lipid profiles in 778 adults. Ann Epidemiol 5: 490–496, 1995

    Article  PubMed  CAS  Google Scholar 

  13. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656–660, 1999

    Article  PubMed  CAS  Google Scholar 

  14. Hosoda H, Kojima M, Matsuo H, Kangawa K: Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279: 909–913, 2000

    Article  PubMed  CAS  Google Scholar 

  15. Lee HM, Wang G, Englander EW, Kojima M, Jr.Greeley GH: Ghrelin, A new gastrointestinal endocrine peptide that stimulates insulin secretion: Enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 143: 185–190, 2002

    Article  PubMed  CAS  Google Scholar 

  16. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB: Ghrelin-a hormone with multiple functions. Front Neuroendocrinol 25: 27–68, 2004

    Article  PubMed  CAS  Google Scholar 

  17. Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J: Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 146: 241–244, 2002

    Article  PubMed  CAS  Google Scholar 

  18. Broglio F, Arvat E, Benso A,Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E: Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 86: 5083–5086, 2001

    Article  PubMed  CAS  Google Scholar 

  19. Y. Date, M. Nakazato, S. Hashiguchi, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S: Ghrelin is present in pancreatic alpha cells of humans and rats and stimulates insulin secretion. Diabetes 51: 124–129, 2002

    Article  PubMed  CAS  Google Scholar 

  20. Relander A, Raiha CE: Differences between the enzymatic and toluidine methods of blood glucose determination. Scand J Clin Lab Invest 15: 221–224, 1963

    Article  CAS  Google Scholar 

  21. Naito HK: Cholesterol: Rewiev of methods, check sample PTS 85–1, Chicago, American Society of Clinical Pathology, pp.1–17, 1985

    Google Scholar 

  22. Frings CS, Fendley TW, Dunn RT, Queen CA: Improved determination of serum lipid by sulphophoshovanilin reaction. Clin Chem 18: 673–674, 1972

    PubMed  CAS  Google Scholar 

  23. Kayamori F, Igarashi K: Effects of dietary nasunin on the serum cholesterol level in rats. Biosci Biotech Biochem 58: 570–571, 1994

    CAS  Google Scholar 

  24. Faure P, Roussel A, Coudray C, Richard MJ, Halimi S, Favier A: Zinc and insulin sensitivity. Biol Trace Elem Res 32: 305–310, 1992

    Article  PubMed  CAS  Google Scholar 

  25. Coleman JE: Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. Annu Rev Biochem 61: 897–946, 1992

    Article  PubMed  CAS  Google Scholar 

  26. Tobia MH, Zdanowicz MM, Wingertzahn MA, McHeffey-Atkinson B, Slonim AE, Wapnir RA.: The role of dietary zinc in modifying the onset and severity of spontaneous diabetes in the BB Wistar rat. Mol Genet Metab 63: 205–213, 1998

    Article  PubMed  CAS  Google Scholar 

  27. Ohly H, Wang Z, Abel J, Gleichmann H: Zinc sulphate induced metallothionein in pancreatic islets and protected against the diabetogenic toxin streptozotocin, Talanta 46: 355–359,1998

    Article  CAS  PubMed  Google Scholar 

  28. Ukkola O: Ghrelin and insulin metabolism. Eur J Clin Invest 33: 183–185: 2003

    Article  PubMed  CAS  Google Scholar 

  29. Gualillo O, Caminos JE, Kojima M, Kangawa K, Arvat E, Ghigo E, Casanueva FF, Dieguez C: Gender and gonadal influences on ghrelin mRNA levels in rat stomach. Eur J Endocrinol 144:687–690, 2001

    Article  PubMed  CAS  Google Scholar 

  30. Matsubara M, Sakata I, Wada R, Yamazaki M, Inoue K, Sakai T: Estrogen modulates ghrelin expression in the female rat stomach. Peptides 25:289–297, 2004

    Article  PubMed  CAS  Google Scholar 

  31. Tschop M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 407: 908–913, 2000

    Article  PubMed  CAS  Google Scholar 

  32. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M: Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 10: 337–345, 2001

    Article  Google Scholar 

  33. Vats V, Yadav SP, Grover JK: Effect of T. foenumgraecum on glycogen content of tissues and the key enzymes of carbohydrate metabolism. J Ethnopharmacol 85: 237–242, 2003

    Article  PubMed  CAS  Google Scholar 

  34. Ravi K, Ramachandran B, Subramanian S: Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin–induced diabetic rats. Biol Pharm Bull 27: 1212–1217, 2004

    Article  PubMed  CAS  Google Scholar 

  35. Lee Y-M, Kim H, Choi H-S, Kang B-H, Han Y-B, Kim S-J: Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats. Phytother Res 13: 555–560, 1999

    Article  PubMed  CAS  Google Scholar 

  36. Brandao-Neto J, Vieira JG, Shuhama T, Russo EM, Piesco RV, Curi PR: Interrelationships of zinc with glucose and insulin metabolism in humans. Biol Trace Elem Res 24: 73–82, 1990

    Article  PubMed  CAS  Google Scholar 

  37. Shisheva A, Gefel D, Shechter Y: Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozocin-induced rats. Diabetes 41: 982–988,1992

    Article  PubMed  CAS  Google Scholar 

  38. Yoshikawa Y, Ueda E, Miyake H, Sakurai H, Kojima Y: Insulinomi-metic bis(maltolato)zinc(II) complex: blood glucose normalizing effect in KK-A(y) mice with type 2 diabetes mellitus. Biochem Biophys Res Commun 281: 1190–1193, 2001

    Article  PubMed  CAS  Google Scholar 

  39. Chen MD, Liou SJ, Lin PY, Yang VC, Alexander PS, Lin WH: Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice. Biol Trace Elem Res 61: 303–311, 1998

    Article  PubMed  CAS  Google Scholar 

  40. Erciyas F, Taneli F, Arslan B, Uslu Y: Glycemic control, oxidative stress, and lipid profile in children with Type 1 diabetes mellitus. Arch Med Res 35: 134–140, 2004

    Article  PubMed  CAS  Google Scholar 

  41. Grundy MS: Diabetes and cardiovascular disease. Circulation 100: 1134–1146, 1999

    PubMed  CAS  Google Scholar 

  42. Prakasam A, Sethupathy S, Pugalendi KV: Hypolipidaemic effect of Casearia esculenta root extracts in streptozotocin induced diabetic rats. Pharmazie 58: 828–832, 2003

    PubMed  CAS  Google Scholar 

  43. Coulston. L, Dandona P: Insulin-like effect of zinc on adipocytes. Diabetes 29: 665–667, 1980

    Article  PubMed  CAS  Google Scholar 

  44. Marreiro DN, Fisberg M, Cozzolino SM: Zinc nutritional status in obese children and adolescents. Biol Trace Elem Res 86: 107–122, 2002

    Article  PubMed  Google Scholar 

  45. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 409: 194–198, 2001

    Article  PubMed  CAS  Google Scholar 

  46. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S: Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87: 240–244, 2002

    Article  PubMed  CAS  Google Scholar 

  47. Ishii S, Kamegai J, Tamura H, Shimizu T, Sugihara H, Oikawa S: Role of Ghrelin in streptozotocin-induced diabetic hyperphagia. Endocrinology 143: 4934–4937, 2002

    Article  PubMed  CAS  Google Scholar 

  48. Masaoka T, Suzuki H, Hosoda H, Ota T, Minegishi Y, Nagata H, Kangawa K, Ishii H: Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes. FEBS Lett 541: 64–68, 2003

    Article  PubMed  CAS  Google Scholar 

  49. Feingold KR, Wiley MH, MacRae G, Moser AH, Lear SR, Siperstein MD: The effect of diabetes mellitus on sterol synthesis in the intact rat. Diabetes 31: 388–395, 1982

    Article  PubMed  CAS  Google Scholar 

  50. Feingold KR, Moser A, Adi S, Soued M, Grunfeld C: Small intestinal fatty acid synthesis is increased in diabetic rats, Endocrinology 127: 2247–2252, 1990

    Article  PubMed  CAS  Google Scholar 

  51. Purnell JQ, Weigle DS, Breen P, Cummings DE: Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 88: 5747–5752, 2003

    Article  PubMed  CAS  Google Scholar 

  52. Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Fanelli CG, Bolli GB, Santeusanio F, De Feo P: Insulin is required for prandial ghrelin suppression in humans. Diabetes 52: 2923–2927, 2003

    Article  PubMed  CAS  Google Scholar 

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Bolkent, S., Yanardag, R., Bolkent, S. et al. The Effect of Zinc supplementation on Ghrelin-Immunoreactive Cells and Lipid Parameters in Gastrointestinal Tissue of Streptozotocin-Induced Female Diabetic Rats. Mol Cell Biochem 286, 77–85 (2006). https://doi.org/10.1007/s11010-005-9095-1

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  • DOI: https://doi.org/10.1007/s11010-005-9095-1

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