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.
Similar content being viewed by others
References
Bray TM, Bettger WJ: The physiological role of zinc as an antioxidant. Free Radic Biol Med 8: 281–291, 1990
Powell SR: The antioxidant properties of zinc. J Nutr 130:1447–1454, 2000
Chausmer AB: Zinc, insulin and diabetes. J Am Coll Nutr 17:109–115, 1998
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
King JC, Shames DM, Woodhouse LR: Zinc homeostasis in humans. J Nutr 130: 1360–1366, 2000
Tapiero H, Tew KD: Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother 57: 399–411, 2003
Ghishan FK, Greene HL: Intestinal transport of zinc in the diabetic rat. Life Sci 32: 1735–1741, 1983
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
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
Lau AL, Failla ML: Urinary excretion of zinc, copper and iron in the streptozotocin- diabetic rat. J Nutr 114: 224–233, 1984
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
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
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
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
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
Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB: Ghrelin-a hormone with multiple functions. Front Neuroendocrinol 25: 27–68, 2004
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
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
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
Relander A, Raiha CE: Differences between the enzymatic and toluidine methods of blood glucose determination. Scand J Clin Lab Invest 15: 221–224, 1963
Naito HK: Cholesterol: Rewiev of methods, check sample PTS 85–1, Chicago, American Society of Clinical Pathology, pp.1–17, 1985
Frings CS, Fendley TW, Dunn RT, Queen CA: Improved determination of serum lipid by sulphophoshovanilin reaction. Clin Chem 18: 673–674, 1972
Kayamori F, Igarashi K: Effects of dietary nasunin on the serum cholesterol level in rats. Biosci Biotech Biochem 58: 570–571, 1994
Faure P, Roussel A, Coudray C, Richard MJ, Halimi S, Favier A: Zinc and insulin sensitivity. Biol Trace Elem Res 32: 305–310, 1992
Coleman JE: Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. Annu Rev Biochem 61: 897–946, 1992
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
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
Ukkola O: Ghrelin and insulin metabolism. Eur J Clin Invest 33: 183–185: 2003
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
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
Tschop M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 407: 908–913, 2000
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
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
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
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
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
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
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
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
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
Grundy MS: Diabetes and cardiovascular disease. Circulation 100: 1134–1146, 1999
Prakasam A, Sethupathy S, Pugalendi KV: Hypolipidaemic effect of Casearia esculenta root extracts in streptozotocin induced diabetic rats. Pharmazie 58: 828–832, 2003
Coulston. L, Dandona P: Insulin-like effect of zinc on adipocytes. Diabetes 29: 665–667, 1980
Marreiro DN, Fisberg M, Cozzolino SM: Zinc nutritional status in obese children and adolescents. Biol Trace Elem Res 86: 107–122, 2002
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-9095-1