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OMEGA-3-FATTY ACIDS IMPROVE INSULIN RESISTANCE AND HYPERGLYCEMIA VIA UPREGULATION OF PDX1 AND NKX6.1 TRANSCRIPTION FACTORS.

Dr Abroo Fatima Qazi, Dr Din Muhammad Shaikh, Komal Siddiqui, Dr Navaid Kazi, Dr Yar Muhammad Nizammani

Background: Poly unsaturated Omega-3-Fatty Acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely acclaimed as having a broad spectrum of therapeutic properties. These Fatty acids have been reported to show beneficial effects in improving the diabetic pathologies like insulin resistance and its consequent dyslipidemia. Objectives Of Study: To observe the health beneficial effects of long chain omega-3-fatty acids on reversing the insulin resistance and correction of its consequent dyslipidemia in Streptozocin induced diabetic rats. Subjects And Methods: An experimental – analytical study was conducted at the ISRA University, Hyderabad and Sindh Agricultural University, Tandojam. 75 Male Wistar Albino rats were selected for this study and were divided into 5 groups, Control group A and experimental groups B,C,D and E, comprising of 15 rats in each group. Group A was taken as non-diabetic control group and was given normal chow diet while group B was taken as diabetic control after inducing diabetes via Streptozocin 65 mg /kg body weight. Omega-3-fatty acids were given in 03 different doses 0.3g, 0.4g and 0.5g per kg body weight to experimental groups C, D and E respectively in which diabetes was induced with Streptozocin similar to diabetic control group. Animal were handled under close supervision during 3 month’s duration experiment. The blood samples and pancreatic tissue were stored and processed in a systemic way. Blood glucose and serum insulin were determined according to standard methods. HOMA-IR was calculated to assess insulin resistance. Pancreatic tissue was used RT-PCR. Collected data was analyzed on SPSS version 21.0. (IBM, corporation, USA) P-value of significance was taken at 0.05. Results: Blood glucose lowering activity of O3FAs was observed at 03 different doses(0.3g, 0.4g and 0.5g). Serum insulin was improved to near normal in experimental groups C,D and E by O3FAs. The O3FAs treated animals revealed expression of major regulatory pancreatic transcription factors like PDX1 & NKX6.1 at different doses. Conclusion: It is concluded that O3FAs by upregulating NKX6.1 and PDX1 genes, transactivated the insulin gene and reduced insulin resistance and dyslipidemia in STZ induced diabetic Wistar rats. Keywords: Omeg-3-Fatty Acids, PDX1, NKx6.1, Insulin Resistance, Dyslipidemia.

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