title: [Effects of early insulin therapy on sterol regulatory element binding protein 1 pathway and lipid accumulation in liver of type 2 diabetic rats].
abstract: OBJECTIVE
  To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 (SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats (DM).
  
  
  METHODS
  A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control (NC), DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6 - 8 U/day). Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein (Bip), oxygen-regulated protein 150 (ORP150), insulin-induced gene 1 (Insig1), SREBP1 and nuclear SREBP1 (nSREBP1) were assayed by Western blot. Adipose tissue mass was measured.
  
  
  RESULTS
  In the DM group, ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 ± 0.02 vs 0.43 ± 0.01 for Bip; 1.11 ± 0.04 vs 1.83 ± 0.03 for ORP150, P < 0.05 for both) and Insig1 decreased (0.25 ± 0.02 vs 0.80 ± 0.07, P < 0.05). And the expressions of SREBP1 and nSREBP1 were elevated (1.03 ± 0.14 vs 0.41 ± 0.01 for SREBP1; 3.63 ± 0.77 vs 0.96 ± 0.20 for nSREBP1, P < 0.05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 ± 0.04 vs 0.67 ± 0.02 for Bip; 1.83 ± 0.03 vs 1.11 ± 0.04 for ORP150; 0.43 ± 0.02 vs 0.25 ± 0.02 for Insig1; 0.46 ± 0.01 vs 1.03 ± 0.14 for SREBP1; 1.65 ± 0.18 vs 3.63 ± 0.77 for nSREBP1, P < 0.05 for all). Furthermore, adipose tissue mass increased (22.4 g ± 3.6 g vs 12.0 g ± 2.6 g, P < 0.05).
  
  
  CONCLUSIONS
  The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats.
authors.affiliation: Department of Endocrinology, Sun Yat-sen University, Guangzhou, China.
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: Jian-ping
authors.initials: JP
authors.lastname: Ye
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Weng
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D007328:Insulin; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1