Amelioration of altered adipokines expression and serine/threonine phosphorylation of IRS1 in alloxan-induced diabetes by Potentilla fulgens and its phytochemical constituents

Authors

  • Shelareen E Sunn Department of Biochemistry, School of Life Sciences, North-Eastern Hill University, Shillong-793022, Meghalaya, India.
  • Donkupar Syiem Department of Biochemistry, School of Life Sciences, North-Eastern Hill University, Shillong-793022, Meghalaya, India.
  • Careen Liza Pakyntein Department of Biochemistry, School of Life Sciences, North-Eastern Hill University, Shillong-793022, Meghalaya, India.

DOI:

https://doi.org/10.30574/gscbps.2021.17.3.0360

Keywords:

Potentilla fulgens, Catechin, -)-epicatechin, IRS1, Adipokines

Abstract

The present study is aimed at investigating the modulation of serine/threonine phosphorylation of IRS1 and the gene expression oftotal IRS1 and adipokines including TNF-α, IL-6 and adiponectin by the plant Potentilla fulgens and its phytochemical constituents catechin and (-)-epicatechin. Alloxan-induced diabetic mice with a two-to three-fold increase in their blood glucose levels were taken for the study. The level of protein expression of total (tIRS1), tyrosine (pIRS1), and serine phosphorylated IRS1 (pIRS1 ser307) was analysed by western blot, and the gene expression level of tIRS1, IL-6, TNF-α, and adiponectin was analysed by real-time PCR. Since evidences strongly suggest that adiponectin, TNF-α, and IL-6 are implicated in insulin resistance and type 2 diabetes, therefore these three adipokines have been targeted in our study with an aim to investigate the anti-inflammatory and antidiabetic effects of our plant Potentillafulgens(PF) andits phytochemicals. The results strongly demonstrates the capability of PF and its phytochemicals to modulate the ser/thr phosphorylation state of IRS1 by downregulating the serine 307 phosphorylation while simultaneously upregulating the tyrosine phosphorylation of IRS1. The results also indicate the ability of the same to alleviate inflammation in alloxan induced diabetes by modulating the expression of the insulin sensitizing hormone adiponectin and the pro-inflammatory cytokines L-6 and TNF-α.

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References

Holst D, Grimaldi PA. New factors in the regulation of adipose differentiation and metabolism. Current Opinion in Lipidology. 2002; 13: 241–245.

Frayn K. N. Adipose tissue as a buffer for daily lipid influx. Diabetologia.2002; 45(9): 1201-10.

Qatanani M and Lazar M A. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes&Development. 2007; 21:1443–1455.

Kwon H and Pessin J. E. Adipokines mediate inflammation and insulin resistance. Frontiers in Endocrinology. 2013; 12(4): 71.

Martinez C. K., Stiles B, Wang Y et al., Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue. Molecular and Cellular Biology. 2005; 25(6): 2498–2510

Vendrell J, Broch M, Vilarrasa N,MolinaA et al., Resistin, Adiponectin, Ghrelin, Leptin, and Proinflammatory Cytokines: Relationships in Obesity. Obesity Research 2004; 12(6): 962-971.

Makki K, Froguel P, and Wolowczuk Isabelle. Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines. ISRN Inflammation. 2013; 5091: 139239.

Haeusler RA, Mc Graw TE, Accili D. Biochemical and cellular properties of insulin receptor signaling. Nature ReviewsMolecular Cell Biology. 2018; 19(1): 31-44.

Ruan H, Lodish HF. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine and Growth Factor Reviews. 2003; 14(5): 447-55.

Syiem D, Syngai G, Khup PZ, Khongwir BS, Kharbuli B and Kayang H, Hypoglycemic effects of Potentilla fulgens L. in normal and alloxan induced diabetic mice.Journal of Etnopharmacology. 2002; 83: 55-61.

Syiem D, Syngai G, Kharbuli B, et al., Anti-tumor activity of crude root extract of Potentilla fulgens. Indian Drugs. 2003; 40(2).

Roy B, Swargiary A, Syiem D, Tandon V. Potentilla fulgens (Family Rosaceae), a medicinal plant of north-east India: a natural anthelminthic? Journal of Parasitic Diseases. 2010; 34(2): 83-8.

Saio V, Syiem D, Sharma R, Dkhar J. Amelioration of age-dependent increase in oxidative stress markers in male mice by extract of Potentilla fulgens.Redox Report. 2016; 21: 130-8.

Anal JMH, Majeed AR, Bez1 G, et al., AK In vitro cytotoxicity of the polar extracts of Potentilla fulgens L. against human cancer cell lines: Detection and isolation of bioactive phenolics. Journal of Chemical and Pharmaceutical Research. 2014; 6(9): 89-95.

Harborne JB. Photochemical Methods, 3rd edition. 1998.

Thabah D, Syiem D, Pakyntein CL, et al. A. Potentillafulgens upregulate GLUT4, AMPK, AKT, and insulin in alloxan-induced diabetic mice: an in vivo and in silico study. Archives in physiology and Biochemistry. 2021; 18: 1-13.

Meng XM, Ma XX, Tian YL,Jiang Q, Wang LL, Shi R,Ding L,Pang SG.Metformin improves the glucose and lipid metabolism via influencing the level of serum total bile acids in rats with streptozotocin-induced type 2 diabetes mellitus. European Review for Medical and Pharmacological Sciences. 2017; 21: 2232-2237.

Twinn DSF, Alfaradhi MZ, Gronert MSM, et al., Downregulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through post-transcriptional mechanisms. Molecular Metabolism. 2014; 20: 3(3):325-33.

Bradford MM.A rapid and sensitive Method for the Quantification of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding.Analytical Biochemistry. 1976; 72: 248- 254.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C (T)) method. Methods (San Diego, Calif.). 2002; 25(4):402–408.

Hotamisligil GS, Shargill NS, Spiegelman BM. adipose expression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance.Science. 1993; 259: 87-91.

Osborn O, Olefskky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nature Medicine. 2012; 18:363-374.

Wellen KE, Hotamisligil GS. Inflammation, stress and diabetes.Journal ofClinical Investigation. 2005; 115: 1111-1119.

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Published

2021-12-30

How to Cite

Sunn, S. E. ., Syiem, D. ., & Pakyntein, C. L. . (2021). Amelioration of altered adipokines expression and serine/threonine phosphorylation of IRS1 in alloxan-induced diabetes by Potentilla fulgens and its phytochemical constituents. GSC Biological and Pharmaceutical Sciences, 17(3), 144–152. https://doi.org/10.30574/gscbps.2021.17.3.0360

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