title: Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice.
abstract: BACKGROUND
  Angiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved.
  
  
  METHODS
  Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks.
  
  
  RESULTS
  The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells.
  
  
  CONCLUSIONS
  These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.
authors: Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: N
authors: N
authors: Mizutani
authors: N
authors: N
authors: Ozaki
authors: Y
authors: Y
authors: Seino
authors: A
authors: A
authors: Fukami
authors: E
authors: E
authors: Sakamoto
authors: T
authors: T
authors: Fukuyama
authors: Y
authors: Y
authors: Sugimura
authors: H
authors: H
authors: Nagasaki
authors: H
authors: H
authors: Arima
authors: Y
authors: Y
authors: Oiso
mesh_terms: D041721:3T3-L1 Cells; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013311:Streptozocin; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D008687:Metformin