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Acta Diabetologica

, Volume 55, Issue 9, pp 935–942 | Cite as

The response of serum Glypican-4 levels and its potential regulatory mechanism to endurance training and chamomile flowers’ hydroethanolic extract in streptozotocin–nicotinamide-induced diabetic rats

  • Farzad Abdolmaleki
  • Ali Heidarianpour
Original Article

Abstract

Aims

Glypican-4 (GPC-4) is a novel adipomyokine that enhances insulin signaling. Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is thought to release GPC-4 and is itself an insulin-regulated enzyme. Beneficial effects of exercise training and chamomile flowers extract (CFE) are shown through activation of PPARγ, which is a promising drug target in diabetes and associated with GPC-4 synthesis. This study investigated the effects of 14-week treadmill running and CFE on serum GPC-4, GPLD1, and insulin levels in streptozotocin–nicotinamide (STZ–NA)-induced diabetic rats.

Methods

Thirty-two STZ–NA-induced diabetic male Wistar rats were randomly assigned to four groups: control (C), training (T), CFE treatment (CFE), and training plus CFE treatment (TCFE) groups. The training groups were exercised on treadmill 5 days/week and the treating groups were fed with 200 mg/kg/day CFE in drinking water for 14 weeks. Finally, serum GPC-4, GPLD1, and insulin levels were analyzed via sandwich ELISA.

Results

Compared to the control group, serum insulin levels were significantly higher in the T, CFE, and TCFE groups (p < 0.05, p < 0.05, p < 0.01, respectively), while OGTT and serum GPLD1 levels were significantly lower in the T, CFE, and TCFE groups (all p < 0.001). Changes in serum GPC-4 levels were not significant. Serum GPLD1 levels were negatively correlated with insulin levels and HOMA-IS (both p < 0.001).

Conclusions

This study suggests that endurance training and CFE may downregulate serum GPLD1 levels in STZ–NA-induced diabetic rats, which associate with the serum insulin profile. However, the results show that endurance training and CFE may not cause serum GPC-4 adaptation in STZ–NA-induced diabetic rats.

Keywords

Exercise training Chamomile Glypican-4 Glycosylphosphatidylinositol-specific phospholipase D Insulin Type 2 diabetes 

Notes

Acknowledgements

This research was supported by Bu-Ali Sina University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Animal experimental procedures were in accordance with institutional guidelines and approved by the ethical committee of laboratory animals Care at Bu-Ali Sina University (BASU), Hamedan, Iran.

Human and Animal rights

No human studies were carried out by the authors for this article.

Informed consent

For this type of study formal consent is not required.

References

  1. 1.
    Iozzo RV, Schaefer L (2015) Proteoglycan form and function: A comprehensive nomenclature of proteoglycans. Matrix Biol 42:11–55CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mitchell F (2012) Obesity: Glypican-4: role in insulin signaling. Nat Rev Endocrinol 8:505CrossRefPubMedGoogle Scholar
  3. 3.
    Tamori Y, Kasuga M (2013) Glypican-4 is a new comer of adipokines working as insulin sensitizer. J Diabetes Investig 4:250–251CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ussar S, Bezy O, Blüher M, Kahn CR (2012) Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine. Diabetes 61:2289–2298CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Song HH, Filmus J (2002) The role of glypicans in mammalian development. Biochem Biophys Acta 1573:241–246CrossRefPubMedGoogle Scholar
  6. 6.
    Kristiansen S, Richter EA (2002) GLUT4-containing vesicles are released from membranes by phospholipase D cleavage of a GPI anchor. Am J Physiol Endocrinol Metab 283:374–382CrossRefGoogle Scholar
  7. 7.
    Deeg MA, Bowen RF, Williams MD, Olson LK, Kirk EA, LeBoeuf RC (2001) Increased expression of GPI-specific phospholipase D in mouse models of type 1 diabetes. Am J Physiol Endocrinol Metab 281:147–154CrossRefGoogle Scholar
  8. 8.
    Schofield JN, Stephens JW, Hurel SJ, Bell KM, deSouza JB, Rademacher TW (2002) Insulin reduces serum glycosylphosphatidylinositol phospholipase D levels in human type I diabetic patients and streptozotocin diabetic rats. Mol Genet Metab 75:154–161CrossRefPubMedGoogle Scholar
  9. 9.
    Qin W, Liang YZ, Qin BY, Zhang JL, Xia N (2016) The clinical significance of glycoprotein phospholipase D levels in distinguishing early stage latent autoimmune diabetes in adults and type 2 diabetes. PLoS ONE 11:1–15Google Scholar
  10. 10.
    Raikwar ND, Bowen-Deeg RF, Du XS, Low MG, Deeg MA (2010) Glycosylphosphatidylinositol-specific phospholipase D improves glucose tolerance. Metab Clin Exp 59:1413–1420CrossRefPubMedGoogle Scholar
  11. 11.
    Li K, Xu X, Hu W et al (2014) Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes. Acta Diabetol 51:981–990CrossRefPubMedGoogle Scholar
  12. 12.
    Oh K-J, Lee DS, Kim WK, Han BS, Lee SC, Bae KH (2017) Metabolic adaptation in obesity and type II diabetes: myokines, adipokines and hepatokines. Int J Mol Sci 18:1–31Google Scholar
  13. 13.
    Liu L, Gu H, Zhao Y, An L, Yang J (2014) Glypican 4 may be involved in the adipose tissue redistribution in high-fat feeding C57BL/6J mice with peroxisome proliferators-activated receptor γ agonist rosiglitazone treatment. Exp Ther Med 8:1813–1818CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wang L, Waltenberger B, Pferschy-Wenzig EM et al (2014) Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 92:73–89CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rashmi S, Shilpy S (2016) Herbs and botanical ingredients with beneficial effects on blood sugar levels in pre-diabetes. Herb Med Open Access 2:1–11Google Scholar
  16. 16.
    Kelleni MT (2016) Chamomile tea potentials in prevention and amelioration of type 2 diabetes mellitus. J Diabetes Metab 7:1CrossRefGoogle Scholar
  17. 17.
    Sebai H, Jabri MA, Souli A et al (2014) Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats. J Ethnopharmacol 152:327–332CrossRefPubMedGoogle Scholar
  18. 18.
    Zemestani M, Rafraf M, Asghari-Jafarabadi M (2016) Chamomile tea improves glycemic indices and antioxidants status in patients with type 2 diabetes mellitus. J Nutr 32:66–72CrossRefGoogle Scholar
  19. 19.
    Kato A, Minoshima Y, Yamamoto J, Adachi I, Watson AA, Nash RJ (2008) Protective effects of dietary chamomile tea on diabetic complications. J Agric Food Chem 56:8206–8211CrossRefPubMedGoogle Scholar
  20. 20.
    Weidner C, Wowro SJ, Rousseau M et al (2013) Antidiabetic effects of chamomile flowers extract in obese mice through transcriptional stimulation of nutrient sensors of the peroxisome proliferator-activated receptor (PPAR) family. PLoS ONE 8:1–16Google Scholar
  21. 21.
    Butcher L, Backx K, Webb R, Thomas A, Roberts A, Morris K (2009) Low-intensity exercise regulates PPAR-γ activity: a molecular rationale for diabetes prevention? In: Abstracts of the 3rd international congress on prediabetes and the metabolic syndrome, pp 71–72Google Scholar
  22. 22.
    Heidarianpour A, Sadeghian E, Gorzi A, Nazem F (2011) The influence of oral magnesium sulfate on skin microvasculature blood flow in diabetic rats. Biol Trace Elem Res 143:344–350CrossRefPubMedGoogle Scholar
  23. 23.
    Ghasemi A, Khalifi S, Jedi S (2014) Streptozotocin–nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiol Hung 101:408–420CrossRefPubMedGoogle Scholar
  24. 24.
    Ghanbari-Niaki A, Farshidi Z, Fathi R (2010) Effects of different endurance training intensities on resting levels of skeletal muscle and liver glycogen concentrations in male rats. Int J Endocrinol Metab 8:79–81Google Scholar
  25. 25.
    Azmir J, Zaidul ISM, Rahman MM et al (2013) Techniques for extraction of bioactive compounds from plant materials: a review. J Food Eng 117:426–436CrossRefGoogle Scholar
  26. 26.
    Hosseinpour M, Mobini-Dehkordi M, Saffar B, Teimori H (2013) Antiproliferative effects of Matricaria chamomilla on Saccharomyces cerevisiae. J HerbMed Pharmacol 2:49–51Google Scholar
  27. 27.
    Bowe JE, Franklin JZ, Hauge-Evans AC, King AJ, Persaud SJ, Jones PM (2014) Assessing glucose homeostasis in rodent models. J Endocrinol 222:13–25CrossRefGoogle Scholar
  28. 28.
    Lasheen NN (2015) Pancreatic functions in high salt fed female rats. Physiol Rep 3:1–13CrossRefGoogle Scholar
  29. 29.
    Du Y, Wei T (2014) Inputs and outputs of insulin receptor. J Protein Cell 5:203–213CrossRefGoogle Scholar
  30. 30.
    Nazem F, Farhangi N, Neshat-Gharamaleki M (2015) Beneficial effects of endurance exercise with Rosmarinus officinalis Labiatae leaves extract on blood antioxidant enzyme activities and lipid peroxidation in streptozotocin-induced diabetic rats. Can J Diabetes 39:229–234CrossRefPubMedGoogle Scholar
  31. 31.
    Sennott J, Morrissey J, Standley PR, Broderick TL (2008) Treadmill exercise training fails to reverse defects in glucose, insulin and muscle GLUT4 content in the db/db mouse model of diabetes. Pathophysiology 15:173–179CrossRefPubMedGoogle Scholar
  32. 32.
    Ito D, Cao P, Kakihana T et al (2015) Chronic running exercise alleviates early progression of nephropathy with upregulation of nitric oxide synthases and suppression of glycation in zucker diabetic rats. PLoS ONE 10:1–21Google Scholar
  33. 33.
    Cerf ME (2013) Beta cell dysfunction and insulin resistance. Front Endocrinol 4:1–12CrossRefGoogle Scholar
  34. 34.
    Choi SB, Jang JS, Hong SM, Jun DW, Park S (2006) Exercise and dexamethasone oppositely modulate β-cell function and survival via independent pathways in 90% pancreatectomized rats. J Endocrinol 190:471–482CrossRefPubMedGoogle Scholar
  35. 35.
    Tahara A, Matsuyama-Yokono A, Nakano R, Someya Y, Shibasaki M (2008) Hypoglycaemic effects of antidiabetic drugs in streptozotocin–nicotinamide-induced mildly diabetic and streptozotocin-induced severely diabetic rats. Basic Clin Pharmacol Toxicol 103:560–568CrossRefPubMedGoogle Scholar
  36. 36.
    Panda S, Kar A (2007) Apigenin (4′,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice. J Pharm Pharmacol 59:1543–1548CrossRefPubMedGoogle Scholar
  37. 37.
    Ramesh B, Pugalendi KV (2006) Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food 9:562–566CrossRefPubMedGoogle Scholar
  38. 38.
    Teixeira-Lemos E, Nunes S, Teixeira F, Reis F (2011) Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol 10:1–15CrossRefGoogle Scholar
  39. 39.
    Zhang X, Wang L, Song Y (2016) Dietary antioxidant vitamins and flavonoids and type 2 diabetes: a review of current epidemiologic evidence. N Am J Med Sci 9:12–16Google Scholar
  40. 40.
    O’Brien KD, Pineda C, Chiu WS, Bowen R, Deeg MA (1999) Glycosylphosphatidylinositol-specific phospholipase D is expressed by macrophages in human atherosclerosis and colocalizes with oxidation epitopes. Circulation 99:2876–2882CrossRefPubMedGoogle Scholar
  41. 41.
    Jin JK, Jang B, Tae Jin H et al (2015) Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease. PLoS ONE 10:1–11Google Scholar
  42. 42.
    Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA (2011) The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. J Nat Rev Immunol 11:1–10CrossRefGoogle Scholar
  43. 43.
    Yoo HJ, Hwang SY, Cho GJ et al (2013) Association of Glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease. J Clin Endocrinol Metab 98:2897–2901CrossRefPubMedGoogle Scholar
  44. 44.
    Traister A, Shi W, Filmus J (2008) Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface. Biochem J 410:503–511CrossRefPubMedGoogle Scholar
  45. 45.
    Zhu HJ, Pan H, Cui Y et al (2014) The changes of serum Glypican4 in obese patients with different glucose metabolism status. J Clin Endocrinol Metab 99:2697–2701CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Exercise Physiology, Faculty of Physical Education and Sport ScienceBu-Ali Sina UniversityHamadanIran

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