The effects of insulin and gliclazide therapy on endoplasmic reticulum stress and insulin sensitivity in liver of type 2 diabetic rats / 中华内科杂志

ABSTRACT

Objective To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2 diabetic rats.Methods A high fat diet plus a low-dose of streptozotocin was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus (DM) group,insulin treatment (INS) group and gliclazide treatment (GT)group; and healthy rats were as normal control group.Diabetic rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and gliclazide respectively for 3 weeks.Protein expression levels of immunoglobulin binding protein (Bip),spliced X-box binding protein 1 (XBP-ls),phosphorylated c-Jun on serine 73 (p-c-Jun),phosphorylated insulin receptor substrate 1 on serine 307 (p-IRS-1),and glucose-6-phosphatase (G6Pase) in liver homogenate were detected by Western blotting.Results Compared with the normal rats,Bip and XBP-Is in the DM group were up-regulated (0.28 ±0.07 vs 0.90 ±0.10 for Bip;0.41 ± 0.07 vs 0.95 ±0.07 for XBP-1 s; both P ＜ 0.01 ) ; p-c-Jun (0.59 ± 0.18 vs 1.94 ± 0.03 ),p-IRS-1( 1.73 ± 0.18 vs 5.32 ± 0.22) and G6Pase (0.11 ± 0.01 vs 0.45 ± 0.01 ) were increased ( all P values ＜0.01 ).In the INS group,all of aforementioned changes were reversed (0.90 ± 0.10 vs 0.25 ± 0.04 for Bip; 0.95 ±0.07 vs 0.47 ±0.01 for XBP-1s; 1.94 ± 0.03 vs 0.50 ±0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ±0.32 for p-IRS-1 ; 0.45 ±0.01 vs 0.15 ±0.02 for G6Pase,all P values ＜0.01 ).In the GT group,all of aforementioned changes were also attenuated ( 0.90 ± 0.10 vs 0.53 ± 00.02 for Bip ; 0.95 ± 0.07 vs 0.78±0.02 for XBP-1s; 1.94 ±0.03 vs 1.33 ±0.11 for p-c-Jun; 5.32 ±0.22 vs 3.13 ±0.02 for p-IRS-1; 0.45 ± 0.01 vs 0.25 ± 0.01 for G6Pase,all P values ＜ 0.05).Furthermore,all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group ( all P values ＜ 0.01 ).Conclusions Both insulin and gliclazide therapy could relieve ER stress and e-Jun N-terminal kinase activity and improved insulin sensitivity.The effect of insulin on Bip,XBP-1s,p-c-Jun,p-IRS-1 and G6Pase protein expressions is more obvious than that of glilcazide,which indicates besides lowering glucose,insulin might have protective effects of anti-inflammation,anti-oxidative stress or stimulation of lipid redistribution.