title: [The effects of insulin and gliclazide therapy on endoplasmic reticulum stress and insulin sensitivity in liver of type 2 diabetic rats].
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-1s), 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-1s 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-1s; 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 ± 0.02 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 c-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 gliclazide, which indicates besides lowering glucose, insulin might have protective effects of anti-inflammation, anti-oxidative stress or stimulation of lipid redistribution.
authors.affiliation: Department of Endocrinology, Sun Yat-sen University, Guangzhou, China. wjianp@mail.sysu.edu.cn
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Bi
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.forename: Meng-yin
authors.initials: MY
authors.lastname: Cai
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Yan-hua
authors.initials: YH
authors.lastname: Zhu
authors.forename: Li-zhen
authors.initials: LZ
authors.lastname: Liao
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Weng
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D005907:Gliclazide / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007328:Insulin; D005907:Gliclazide