Modulation of Glucose Homeostasis in Rats Treated with Bacterial Lipopolysaccharide: Role of L-Arginine Counter-Strategy

Abstract

Lipopolysaccharide (LPS), an endotoxin derived from the outer membrane of Gram-negative bacteria, mediates a local or systemic inflammatory response. Its action is carried out through stimulation of Tolllike receptor 4 (TLR4) activity and subsequently, production of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-gamma (INF- γ). The purpose of this study was to assess the effect of L-arginine (L-Arg) on endocrine pancreas function in rats treated with LPS. Therefore, rats were weighed, randomly divided into 4 equal groups (20 rats/group) as each group using 4 replications (n=5)and intraperitoneally injected as follow: Control group (saline, 1ml/Kg b.wt for 7 consecutive days), LPS group (LPS, 1 mg/kg b.wt once), L-Arg group (L-Arg, 10 mg/kg b.wt, for 7 days), and LPS+L-Arg group (L-Arg, 10 mg/kg b.wt, for 7 days then once injected with LPS, 1mg/kg). Serum IL-6, glucose and insulin levels were assessed at 6, 12, 24, and 72 hours after LPS or saline injection. Histological examination of the pancreas tissue was also performed. Serum IL-6 elevated significantly 6 and 12 hours after LPS injection and retrieved at 24 and 72 hours. Association of LPS and L-Arg potentiate IL-6 production at 6 and 12 hours higher than that in L-Arg-treated group. Serum glucose levels were declined in single LPS treated rats 6 and 12 hours and recovered at 24 and 72 hours after LPS injection. On contrary, Serum glucose levels were elevated 6 and 12 hours and declined near to control level 24 and 72 h after L-Arg injection. However, insulin levels were slightly elevated 12, 24 and 72 hours after LPS injection and 12 hours after LPS+L-Arg injection the rescued around the normal values at 24 and 72 hours. On contrary, serum insulin level decrease at 6 hours after L-Arg injection then recovered to control level. Histologically, rats treated with LPS showed necrosis, vacuolation in islets of Langerhans with infiltration of inflammatory cells. Pre-treatment of L-Arg prior LPS attenuated the alteration in pancreas tissue architecture. However, Rats treated with L-Arg showed normal pancreas tissue. In conclusion, the results of this study support the hypothesized relationship between L-Arg and modulation of glucose metabolism and suggest that L-Arg may have a dual role in the modulation of glucose homeostasis depending on intensity and stage of inflammation.

Keywords

• insulin
• l-arginine
• lipopolysaccharides
• nitric oxide
• pancreas.