title: Effect of hepatic insulin expression on lipid metabolism in diabetic mice.
abstract: BACKGROUND
  Hypertriglyceridemia is a common lipid disorder that is characterized by elevated plasma levels of triglyceride (TG)-rich particles, such as very low-density lipoprotein (VLDL), in poorly controlled diabetes. The aim of the present study was to determine the potential therapeutic effect of hepatic insulin production on hypertriglyceridemia in mice.
  
  
  METHODS
  Mice were induced diabetic and hypertriglyceridemic by streptozotocin (STZ) treatment. Using an adenovirus-mediated gene transfer approach, we delivered rat preproinsulin cDNA into the liver of diabetic mice and then determined plasma TG metabolism. To investigate the mechanism by which hepatic insulin improves TG metabolism, we determined hepatic expression of apolipoprotein C-III (ApoC-III), a structural moiety and functional inhibitor of VLDL-TG catabolism.
  
  
  RESULTS
  Plasma VLDL-TG levels were markedly elevated in STZ-treated mice, and were accompanied by hyperglycemia and hypertriglyceridemia. These metabolic abnormalities were restored to near normal following hepatic insulin production in insulin vector-treated diabetic mice. In contrast, hypertriglyceridemia and hyperglycemia persisted in control vector-treated diabetic animals. Hepatic ApoC-III expression became deregulated secondary to insulin deficiency, contributing to impaired TG metabolism in diabetic mice. Hepatic insulin production suppressed excessive hepatic ApoC-III production to basal levels.
  
  
  CONCLUSIONS
  Hepatic insulin production is efficacious in correcting hypertriglyceridemia associated with insulin deficiency in diabetic mice.
authors: Department of Endocrinology & Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Shen
authors: S
authors: Qu
authors: Division of Pediatric Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Ting
authors: T
authors: Zhang
authors: Division of Pediatric Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: H Henry
authors: HH
authors: Dong
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D053305:Apolipoprotein C-III; D005230:Fatty Acids, Nonesterified; D000071161:Forkhead Box Protein O1; D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; D014280:Triglycerides; C013737:preproinsulin
keywords: 1型糖尿病; apolipoprotein C-III; forkhead box protein O1; hepatic insulin production; hypertriglyceridemia; mice; type 1 diabetes; 叉头框蛋白01; 小鼠; 肝脏胰岛素表达; 载脂蛋白C- III; 高甘油三酯血症