Insulin Down-regulates Resistin MRNA Through the Synthesis of Protein(s) That Could Accelerate the Degradation of Resistin MRNA in 3T3-L1 Adipocytes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2003 Mar 11

PMID 12627322

Citations 11

Authors

J Kawashima

K Tsuruzoe

H Motoshima

A SHIRAKAMI

K Sakai

Y Hirashima

T Toyonaga

E Araki

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Resistin is a peptide secreted by adipocytes and recognized as a hormone that could link obesity to insulin resistance. This study was designed to examine the effect and mechanism(s) of insulin on resistin expression in 3T3-L1 adipocytes.

Methods: Differentiated 3T3-L1 adipocytes were stimulated with insulin and resistin mRNA expression was examined by Northern blot analysis. In some experiments, the insulin signal was blocked by several chemical inhibitors or overexpression of a dominant negative form (Deltap85) of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase).

Results: Insulin treatment caused a reduction of resistin mRNA in time-dependent and dose-dependent manners in 3T3-L1 adipocytes. Pre-treatment with PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, or SB203580, an inhibitor of p38 mitogen-activated protein-kinase (p38 MAP-kinase) pathway, did not influence insulin-induced reduction of resistin mRNA. Inhibition of PI 3-kinase by LY294002 or Deltap85 also failed to block insulin-induced reduction of resistin mRNA. Cycloheximide, a protein synthesis inhibitor, completely blocked insulin-induced reduction of resistin mRNA. Actinomycin D, a RNA synthesis inhibitor, also blocked insulin-induced reduction of resistin mRNA, and the decreasing rate of resistin mRNA in cells treated with insulin alone was faster than that with actinomycin D.

Conclusion/interpretation: Insulin downregulates resistin mRNA via PI 3-kinase, ERK or p38 MAP-kinase independent pathways in 3T3-L1 adipocytes. The downregulation mechanism of resistin mRNA by insulin would be an indirect event through the synthesis of novel protein(s) that could accelerate the degradation of resistin mRNA.

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References

Saltiel A . Series introduction: the molecular and physiological basis of insulin resistance: emerging implications for metabolic and cardiovascular diseases. J Clin Invest. 2000; 106(2):163-4. PMC: 314314. DOI: 10.1172/JCI10533. View

Coffer P, van Puijenbroek A, Burgering B, Koenderman L, Bos J, Kruijer W . Insulin activates Stat3 independently of p21ras-ERK and PI-3K signal transduction. Oncogene. 1997; 15(21):2529-39. DOI: 10.1038/sj.onc.1201429. View

Hotamisligil G, Shargill N, Spiegelman B . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993; 259(5091):87-91. DOI: 10.1126/science.7678183. View

Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M . Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes. 2002; 51(6):1737-44. DOI: 10.2337/diabetes.51.6.1737. View

Kahn B, Flier J . Obesity and insulin resistance. J Clin Invest. 2000; 106(4):473-81. PMC: 380258. DOI: 10.1172/JCI10842. View

Savage D, Sewter C, Klenk E, Segal D, Vidal-Puig A, Considine R . Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001; 50(10):2199-202. DOI: 10.2337/diabetes.50.10.2199. View

Vaulont S, Kahn A . Transcriptional control of metabolic regulation genes by carbohydrates. FASEB J. 1994; 8(1):28-35. DOI: 10.1096/fasebj.8.1.8299888. View

BAUMANN C, Ribon V, Kanzaki M, Thurmond D, Mora S, Shigematsu S . CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature. 2000; 407(6801):202-7. DOI: 10.1038/35025089. View

Zhande R, Mitchell J, Wu J, Sun X . Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1. Mol Cell Biol. 2002; 22(4):1016-26. PMC: 134643. DOI: 10.1128/MCB.22.4.1016-1026.2002. View

10.

Kayali A, Austin D, Webster N . Stimulation of MAPK cascades by insulin and osmotic shock: lack of an involvement of p38 mitogen-activated protein kinase in glucose transport in 3T3-L1 adipocytes. Diabetes. 2000; 49(11):1783-93. DOI: 10.2337/diabetes.49.11.1783. View

11.

Haugen F, Jorgensen A, Drevon C, Trayhurn P . Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett. 2001; 507(1):105-8. DOI: 10.1016/s0014-5793(01)02968-4. View

12.

De Los Pinos E , Fernandez De Mattos S , Joaquin M, Tauler A . Insulin inhibits glucocorticoid-stimulated L-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression by activation of the c-Jun N-terminal kinase pathway. Biochem J. 2001; 353(Pt 2):267-73. PMC: 1221568. DOI: 10.1042/0264-6021:3530267. View

13.

Shimomura I, Hammer R, Ikemoto S, Brown M, Goldstein J . Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999; 401(6748):73-6. DOI: 10.1038/43448. View

14.

Ribon V, Saltiel A . Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-Cbl in 3T3-L1 adipocytes. Biochem J. 1997; 324 ( Pt 3):839-45. PMC: 1218500. DOI: 10.1042/bj3240839. View

15.

Nagaev I, Smith U . Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun. 2001; 285(2):561-4. DOI: 10.1006/bbrc.2001.5173. View

16.

Rajala M, Lin Y, Ranalletta M, Yang X, Qian H, Gingerich R . Cell type-specific expression and coregulation of murine resistin and resistin-like molecule-alpha in adipose tissue. Mol Endocrinol. 2002; 16(8):1920-30. DOI: 10.1210/me.2002-0048. View

17.

Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R . Isoproterenol inhibits resistin gene expression through a G(S)-protein-coupled pathway in 3T3-L1 adipocytes. FEBS Lett. 2001; 500(1-2):60-3. DOI: 10.1016/s0014-5793(01)02588-1. View

18.

Steppan C, Bailey S, Bhat S, Brown E, Banerjee R, Wright C . The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818):307-12. DOI: 10.1038/35053000. View

19.

OBrien R, GRANNER D . Regulation of gene expression by insulin. Physiol Rev. 1996; 76(4):1109-61. DOI: 10.1152/physrev.1996.76.4.1109. View

20.

Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K . The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001; 7(8):941-6. DOI: 10.1038/90984. View