Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid.

Abstract

Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs. In the present study, we observed that oral supplementation of AA prevented STZ-induced type 2 DM in Wistar rats by restoring hyperglycemia, plasma levels of TNF-α and IL-6; adipose tissue NF-kB and lipocalin 2 (LPCLN2) and pancreatic tissue NF-kB and 5- and 12- lipoxygenase enzymes to normal. AA treatment enhanced insulin sensitivity and plasma lipoxin A4 (LXA4) levels, a potent anti-inflammatory molecule derived from AA. These results are supported by our previous studies wherein it was noted that plasma phospholipid content of AA and circulating LXA4 levels are low in those with type 2 DM. In a preliminary study, we also noted that high-fat-diet (HFD)-induced type 2 DM in Wistar rats can be prevented by oral supplementation of AA. These results suggest AA has anti-inflammatory and anti-diabetic actions by enhancing the production of its anti-inflammatory metabolite LXA4.

• Authors: Naveen K V Gundala, Vegi G M Naidu, Undurti N Das
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 496 Issue 1 Pg. 105-113 (01 29 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 29309791 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Hypoglycemic Agents
• Inflammation Mediators
• Lipoxins
• lipoxin A4
• Arachidonic Acid
• Streptozocin

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Arachidonic Acid (administration & dosage)
• Cytokines (immunology)
• Diabetes Mellitus, Type 2 (chemically induced, drug therapy, immunology)
• Dose-Response Relationship, Drug
• Hypoglycemic Agents (administration & dosage)
• Inflammation Mediators (immunology)
• Lipoxins (immunology)
• Male
• Rats
• Rats, Wistar
• Streptozocin
• Treatment Outcome