Ameliorating Effects of Omega-3 Fatty Acids on Underlying Mechanisms of Type 2 Diabetes

Main Article Content

Abroo Fatima Qazi
Din Muhammad Shaikh

Abstract

Aims: The current study investigated the effects of polyunsaturated Omega-3-fatty acids on underlying mechanism linked with diabetes in streptozocin induced type 2 diabetic Wistar rats.

Study Design:  Experimental analytical Study.

Place and Duration of Study: The study was conducted at Isra University Hyderabad and Sindh Agricultural University, Tandojam between November 2016 and November 2018.

Methodology: Seventy-five Wistar rats were assorted to five groups (15 rats per group): negative control group A and positive control group B and experimental groups C, D and E. Rats within group B,C,D, and E were injected with streptozocin (65 mg/kg body weight) to induce diabetes. Experimental groups C, D and E received Omega-3-fatty acid supplemented food in 0.3 g, 0.4 g and 0.5 g/kg bodyweight dosage for 12 weeks, respectively.

Results: Omega-3-fatty acids treated rats showed significant decrease in blood glucose level and rise in serum insulin as compared to positive control group (p-value = 0.001). At the same time, they showed significantly increased expression of insulin gene along with transcription factors: PDX1 and NKX6.1 as compared to group A (p-value = 0.001).

Conclusion: It is concluded that O3FAs reduces insulin resistance in Streptozocin-induced diabetic Wistar rats by modulating the transcription factors essential for insulin gene expression.

Keywords:
Diabetes mellitus, NKX6.1, Omega-3-Fatty Acids, PDX1, streptozocin.

Article Details

How to Cite
Fatima Qazi, A., & Muhammad Shaikh, D. (2020). Ameliorating Effects of Omega-3 Fatty Acids on Underlying Mechanisms of Type 2 Diabetes. Journal of Pharmaceutical Research International, 31(6), 1-7. https://doi.org/10.9734/jpri/2019/v31i630379
Section
Original Research Article

References

Guo S, Dai C, Guo M, Taylor B, Harmon JS, Sander M, Robertson RP, Powers AC, Stein R. Inactivation of specific β cell transcription factors in type 2 diabetes. J Clin Invest. 2013;123:3305-16.

Hayes HL, Moss LG, Schisler JC, Haldeman JM, Zhang Z, Rosenberg PB, Newgard CB, Hohmeier HE. Pdx-1 activates islet α-and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2. Mol Cell Biol. 2013;33:4017-29.

Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S, Haataja L, Cirulli V, Blelloch R. Controlled induction of human pancreatic progenitors produces functional beta‐like cells in vitro. The EMBO. 2015;34:1759-72.

Abuzgaia AM, Hardy DB, Arany E. Regulation of postnatal pancreatic Pdx1 and downstream target genes after gestational exposure to protein restriction in rats. Reproduction. 2015;149:293-303.

Maganti AV, Maier B, Tersey SA, Sampley ML, Mosley AL, Özcan S, Pachaiyappan B, Woster PM, Hunter CS, Stein R, Mirmira RG. Transcriptional activity of the islet β cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9. J Biol Chem. 2015;290:9812-22.

Malenczyk K, Szodorai E, Schnell R, Lubec G, Szabó G, Hökfelt T, Harkany T. Secretagogin protects Pdx1 from proteasomal degradation to control a transcriptional program required for β cell specification. Mol Metab. 2018;14:108-20.

Van der Meulen T, Huising MO. The role of transcription factors in the transdifferentiation of pancreatic islet cells. J Mol Endocrinol. 2015;54:R103.

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clinl Sci. 2009;117:243-9.

Mazaherioun M, Saedisomeolia A, Javanbakht MH, Koohdani F, Eshraghian MR, Djalali M. Beneficial effects of n-3 polyunsaturated fatty acids on adiponectin levels and AdipoR gene expression in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind clinical trial. Arch Med Sci. 2017;13: 716.

Kunst A, Draeger B, Ziegenhorn J. In: Bergmeyer. Methods of Enzymatic Analysis, 3rd ed. Volume VI, Metabolites 1: Carbohydrates. 1984;163-172.

Wu AH. Tietz clinical guide to laboratory tests-E-book. Elsevier Health Sciences; 2006.

Memon B, Karam M, Al-Khawaga S, Abdelalim EM. Enhanced differentiation of human pluripotent stem cells into pancreatic progenitors co-expressing PDX1 and NKX6. 1. Stem Cell Res Ther. 2018;9:15.

Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, Yang C, Pannikar A, Doliba N, Zhang T, Stoffers DA. Pdx1 maintains β cell identity and function by repressing an α cell program. Cell Metabol. 2014;19:259-71.

Aigha II, Memon B, Elsayed AK, Abdelalim EM. Differentiation of human pluripotent stem cells into two distinct NKX6. 1 populations of pancreatic progenitors. Stem Cell Res Ther. 2018;9:83.

Salim de Castro G, Deminice R, Cordeiro Simões-Ambrosio L, C Calder P, A Jordão A, Vannucchi H. Dietary docosahexaenoic acid and eicosapentaenoic acid influence liver triacylglycerol and insulin resistance in rats fed a high-fructose diet. Mar Drugs. 2015;13:1864-81.

Eraky SM, Abdel-Rahman N, Eissa LA. Modulating effects of omega-3 fatty acids and pioglitazone combination on insulin resistance through toll-like receptor 4 in type 2 diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2018;136:123-9.

Lamping KG, Nuno DW, Coppey LJ, Holmes AJ, Hu S, Oltman CL, Norris AW, Yorek MA. Modification of high saturated fat diet with n‐3 polyunsaturated fat improves glucose intolerance and vascular dysfunction. Diabetes Obes Metab. 2013; 15:144-52.

Matravadia S, Herbst EA, Jain SS, Mutch DM, Holloway GP. Linoleic and a-linolenic acid both prevent insulin resistance but have divergent impacts on skeletal muscle mitochondrial bioenergetics in obese Zucker rats. Am J Physiol Endocrinol Metab. 2014;E102-E114.

Nardi F, Lipina C, Magill D, Hassan RH, Hajduch E, Gray A, Hundal HS. Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A. PloS one. 2014;9: e92255.

Coelho OG, da Silva BP, Rocha DM, Lopes LL, Alfenas RD. Polyunsaturated fatty acids and type 2 diabetes: Impact on the glycemic control mechanism. Crit Rev Food Sci Nutr. 2017;57:3614- 9.

Allam-Ndoul B, Guénard F, Barbier O, Vohl MC. Effect of n-3 fatty acids on the expression of inflammatory genes in THP-1 macrophages. Lipids Health Dis. 2016; 15:69.

De Castro GS, Calder PC. Non-alcoholic fatty liver disease and its treatment with n-3 polyunsaturated fatty acids. Clin Nutr. 2018;37:37-55.

Zárate R, el Jaber-Vazdekis N, Tejera N, Pérez JA, Rodríguez C. Significance of long chain polyunsaturated fatty acids in human health. Clin Transl Med. 2017;6: 25.