Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice

N. Mizutani, N. Ozaki, Y. Seino, A. Fukami, E. Sakamoto, T. Fukuyama, Y. Sugimura, H. Nagasaki, H. Arima, Y. Oiso

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18 Citations (Scopus)

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. Conclusion: These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalExperimental and Clinical Endocrinology and Diabetes
Volume120
Issue number3
DOIs
Publication statusPublished - 01-01-2012

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Angiopoietins
Nonesterified Fatty Acids
Up-Regulation
Insulin
Messenger RNA
Metformin
Proteins
3T3-L1 Cells
White Adipose Tissue
Brown Adipose Tissue
Fatty Acids
High Fat Diet
Streptozocin
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Palmitates
Liver
Linoleic Acid
Adipocytes
Hepatocellular Carcinoma

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Mizutani, N. ; Ozaki, N. ; Seino, Y. ; Fukami, A. ; Sakamoto, E. ; Fukuyama, T. ; Sugimura, Y. ; Nagasaki, H. ; Arima, H. ; Oiso, Y. / Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice. In: Experimental and Clinical Endocrinology and Diabetes. 2012 ; Vol. 120, No. 3. pp. 139-144.
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Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice. / Mizutani, N.; Ozaki, N.; Seino, Y.; Fukami, A.; Sakamoto, E.; Fukuyama, T.; Sugimura, Y.; Nagasaki, H.; Arima, H.; Oiso, Y.

In: Experimental and Clinical Endocrinology and Diabetes, Vol. 120, No. 3, 01.01.2012, p. 139-144.

Research output: Contribution to journalArticle

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T1 - Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice

AU - Mizutani, N.

AU - Ozaki, N.

AU - Seino, Y.

AU - Fukami, A.

AU - Sakamoto, E.

AU - Fukuyama, T.

AU - Sugimura, Y.

AU - Nagasaki, H.

AU - Arima, H.

AU - Oiso, Y.

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Y1 - 2012/1/1

N2 - 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. Conclusion: These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

AB - 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. Conclusion: These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

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