Skip to main content

Advertisement

SpringerLink
Log in

Variations in the mRNA expression level of UDP-GlcNAc epimerase/ManNAc kinase and neuraminidase 1 genes in organs of type 2 diabetic animals

  • Short Communication
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Sialic acid and its associated metabolic enzymes have emerged as important components of the pathophysiology of type 2 diabetes (T2D). There is an elevation in the serum concentration of sialic acid in humans and animals with T2D. The present study investigated the modulation of mRNA expression level of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and neuraminidase 1 (NEU1) genes in some organs of type 2 diabetic rats. T2D was induced using fructose-streptozotocin model and eight weeks after the induction of diabetes, sialic acid was assayed in the blood and organs (adipose tissue, brain, colon, kidney, liver, pancreas, skeletal muscle and spleen) followed by quantification of mRNA expression level of GNE and NEU1 genes by qPCR. The results showed a significant (P < 0.05) increase in sialic acid level in the serum and all the afore-mentioned organs investigated except in the adipose tissue and skeletal muscle of the diabetic rats compared the normal control. The expression GNE gene was only increased in the pancreas (1.8-fold) of the diabetic rats while there was a decrease in the expression of the gene in the colon. In contrast, the expression of NEU1 gene was increased in the spleen (3.5-fold), brain (2.2-fold), liver (1.9-fold), colon (1.5-fold) and kidney of the diabetic rats. It was concluded that the elevated level of sialic acid in the organs of diabetic rats, except the pancreas, might not be due to increased endogenous synthesis of sialic acid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Abbreviations

ELISA:

Enzyme-linked immunosorbent assay

FBG:

Fasting Blood Glucose

GNE:

UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase

HOMA-β:

homeostasis model assessment for β-cells damage

HOMA- IR:

homeostasis model assessment for insulin resistance

NC:

Normal Control Group

NEU1:

neuraminidase 1

STZ:

Streptozotocin

TD:

Type 2 Diabetic Group

References

  1. Ghosh, S.: Sialic acid and biology of life: An introduction. In: Ghosh, S. (ed.) Sialic acids and sialoglycoconjugates in the biology of life, health and disease, pp 1–61. Elsevier Science, Netherlands (2020)

    Google Scholar 

  2. Crook, M.A., Pickup, J.C., Lumb, P.J., Georgino, F., Webb, D.J., Fuller, J.H.: Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study. Diabetes Care. 24, 316–322 (2001)

    Article  CAS  Google Scholar 

  3. Khalili, P., Sundström, J., Jendle, J., Lundin, F., Jungner, I., Nilsson, P.M.: Sialic acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort: the Värmland survey. Prim. Care Diabetes 8, 352–357 (2014)

    Article  Google Scholar 

  4. Varma, V., Varma, M., Varma, A., Kumar, R., Bharosay, A., Vyas, S.: Serum total sialic acid and highly sensitive C-reactive protein: Prognostic markers for the diabetic nephropathy. J. Lab. Phys. 8, 25 (2016)

    CAS  Google Scholar 

  5. Ibrahim, M.A., Abdulkadir, A., Onojah, A., Sani, L., Adamu, A., Abdullahi, H.: Modulation of sialic acid levels among some organs during insulin resistance or hyperglycemic states. Mol. Cell. Biochem. 411, 235–239 (2016)

    Article  CAS  Google Scholar 

  6. Pari, L., Rathinam, A.: Anti-diabetic effect of myrtenal on plasma and tissue glycoproteins components in STZ induced experimental diabetic rats. J. Dis. Med. Plants. 2, 11–16 (2016)

    Google Scholar 

  7. Pickup, J.C., Day, C., Bailey, C.J., Samuel, A., Chusney, G.D., Garland, H.O., Hamilton, K., Balment, R.J.: Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation of sialic acid concentrations by insulin deficiency. Life Sci. 57, 1383–1391 (1995)

    Article  CAS  Google Scholar 

  8. Tomino, Y., Inoue, W., Watanabe, S., Yagame, M., Eguchi, K., Nomoto, Y., Sakai, H.: Detection of glomerular sialic acids in patients with diabetic nephropathy. Am. J. Nephrol. 8, 21–26 (1988)

    Article  CAS  Google Scholar 

  9. Bermingham, M.L., Colombo, M., Mcgurnaghan, S.J., Blackbourn, L.A., Vučković, F., Baković, M.P., Trbojević-Akmačić, I., Lauc, G., Agakov, F., Agakova, A.S.: N-glycan profile and kidney disease in type 1 diabetes. Diabetes Care 41, 79–87 (2018)

    Article  CAS  Google Scholar 

  10. Venerando, B., Fiorilli, A., Croci, G., Tringali, C., Goi, G., Mazzanti, L., Curatola, G., Segalini, G., Massaccesi, L., Lombardo, A.: Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients. Blood. 99, 1064–1070 (2002)

    Article  CAS  Google Scholar 

  11. Saatov, T., Isaev, E., Mzh, E., Nikolaeva, N., Salikhodzhaeva, D.: Content, intensity of exchange, and metabolic interaction of phospholipids and glycolipids in various tissues in experimental diabetes (abstract). Biokhimiia. 48, 1988–1994 (1983)

    CAS  PubMed  Google Scholar 

  12. Bozic, J., Markotic, A., Cikes-Culic, V., Novak, A., Borovac, J.A., Vucemilovic, H., Trgo, G., Kurir, T.: Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes. J. Diabetes. 10, 130–139 (2018)

    Article  CAS  Google Scholar 

  13. Reinke, S.O., Lehmer, G., Hinderlich, S., Reutter, W.: Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis. Biol. Chem. 390, 591–599 (2009)

    Article  CAS  Google Scholar 

  14. Hinderlich, S., Weidemann, W., Yardeni, T., Horstkorte, R., Huizing, M.: UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE): a master regulator of sialic acid synthesis. Top. Curr. Chem. 366, 97–137 (2015)

    Article  CAS  Google Scholar 

  15. Li, Y., Chen, X.: Sialic acid metabolism and sialyltransferases: natural functions and applications. App. Microbiol. Biotechnol. 94, 887–905 (2012)

    Article  CAS  Google Scholar 

  16. Alghamdi, F., Guo, M., Abdulkhalek, S., Crawford, N., Amith, S.R., Szewczuk, M.R.: A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes. Cell. Signal 26, 1355–1368 (2014)

    Article  CAS  Google Scholar 

  17. Cohen-Forterre, L., Andre, J., Mozere, G., Peyroux, J., Sternberg, M.: Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats: Influence of insulin and sorbinil treatments. Biochem. Pharm. 40, 507–513 (1990)

    Article  CAS  Google Scholar 

  18. Fougerat, A., Pan, X., Smutova, V., Heveker, N., Cairo, C.W., Issad, T., Larrivée, B., Medin, J.A., Pshezhetsky, A.V.: Neuraminidase 1 activates insulin receptor and reverses insulin resistance in obese mice. Mol. Metab. 12, 76–88 (2018)

    Article  CAS  Google Scholar 

  19. Miyagi, T.: Aberrant expression of sialidase in cancer and diabetes. In: Taniguchi, N., Suzuki, A., Ito, Y., Narimatsu, H., Kawasaki, T., Hase, S. (eds.) Experimental glycoscience, pp. 329–332. Springer, Tokyo (2008)

    Chapter  Google Scholar 

  20. Wilson, R., Islam, M.S.: Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes. Pharmacol. Rep. 64, 129–139 (2012)

    Article  CAS  Google Scholar 

  21. Bako, H.Y., Ibrahim, M.A., Isah, M.S., Ibrahim, S.: Inhibition of JAK-STAT and NF-κB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes. Life Sci. 239, 117045 (2019)

    Article  CAS  Google Scholar 

  22. Schmittgen, T.D., Livak, K.J.: Analyzing real-time PCR data by the comparative CT method. Nat. Prot. 3, 1101 (2008)

    Article  CAS  Google Scholar 

  23. Jennemann, R., Kaden, S., Volz, M., Nordström, V., Herzer, S., Sandhoff, R., Gröne, H.J.: Gangliosides modulate insulin secretion by pancreatic beta-cells under glucose stress. Glycobiology. 30, 722–734 (2020)

    Article  CAS  Google Scholar 

  24. Pshezhetsky, A.V., Hinek, A.: Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors. Glycoconj. J. 28, 441 (2011)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the TetFund, Nigeria, ABU Desk Office for some of the funds. The comments of Prof S. Ibrahim, Directorate of Research and Innovation, ABU, Zaria at the initial preparation of the manuscript is also acknowledged.

Funding

Part funding support was received from the TetFund, Nigeria, ABU Desk Office.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria

    Mayen David Inim, Mohammed Auwal Ibrahim & Elewechi Onyike

  2. Department of Biochemistry, Umaru Musa Yar’adua University, Katsina, Nigeria

    Murtala Bindawa Isah

Authors
  1. Mayen David Inim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed Auwal Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Murtala Bindawa Isah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elewechi Onyike
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: MAI, Methodology: MDI, MBI, MAI, EO; Formal analysis and investigation: MDI, MBI, MAI, EO; Writing - original draft preparation: MBI, MAI; Writing -review and editing: MAI, EO, Funding acquisition: MDI, EO, MAI; Resources: MAI, EO; Supervision: MAI, EO.

Corresponding author

Correspondence to Mohammed Auwal Ibrahim.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest related to this work.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inim, M.D., Ibrahim, M.A., Isah, M.B. et al. Variations in the mRNA expression level of UDP-GlcNAc epimerase/ManNAc kinase and neuraminidase 1 genes in organs of type 2 diabetic animals. Glycoconj J 38, 129–134 (2021). https://doi.org/10.1007/s10719-021-09979-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-021-09979-7

Keywords

Search

Navigation