+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Increased insulin receptor substrate-1 and enhanced skeletal muscle insulin sensitivity in mice lacking CCAAT/enhancer-binding protein beta



Increased insulin receptor substrate-1 and enhanced skeletal muscle insulin sensitivity in mice lacking CCAAT/enhancer-binding protein beta



Journal of Biological Chemistry 275(19): 14173-14181



CCAAT/enhancer-binding protein beta (C/EBPbeta) controls gene transcription and metabolic processes in a variety of insulin-sensitive tissues; however, its role in regulating insulin responsiveness in vivo has not been investigated. We performed hyperinsulinemic-euglycemic clamps in awake, non-stressed, chronically catheterized adult mice homozygous for a deletion in the gene for C/EBPbeta (C/EBPbeta(-/-)). Fasting plasma insulin, glucose, and free fatty acid (FFA) levels were significantly lower in C/EBPbeta(-/-) mice compared with wild-type (WT) controls. Acute hyperinsulinemia (4 h) suppressed hepatic glucose production, phosphoenolpyruvate carboxykinase mRNA, and plasma FFA to a similar extent in WT and C/EBPbeta(-/-) mice, suggesting that C/EBPbeta deletion does not alter the metabolic and gene regulatory response to insulin in liver and adipose tissue. In contrast, using submaximal (5 milliunits/kg/min) and maximal (20 milliunits/kg/min) insulin infusions, whole-body glucose disposal was 77% (p < 0.01) and 33% (p < 0.05) higher in C/EBPbeta(-/-) mice, respectively, compared with WT mice. Maximal insulin-stimulated 3-O-methylglucose uptake in isolated soleus muscle was 54% greater in C/EBPbeta(-/-) mice (p < 0.05). Furthermore, insulin-stimulated insulin receptor and Akt Ser(473) phosphorylation and phosphatidylinositol 3-kinase activity were 1.6-2.5-fold greater in skeletal muscle from C/EBPbeta(-/-) mice compared with WT mice. The level of insulin receptor substrate-1 protein was increased 2-fold in skeletal muscle from C/EBPbeta(-/-) mice. These results demonstrate that C/EBPbeta deletion decreases plasma FFA levels and increases insulin signal transduction specifically in skeletal muscle, and both contribute to increased whole-body insulin sensitivity.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010824572

Download citation: RISBibTeXText

PMID: 10747954

DOI: 10.1074/jbc.m000764200


Related references

A nucleoprotein complex containing CCAAT/enhancer-binding protein beta interacts with an insulin response sequence in the insulin-like growth factor-binding protein-1 gene and contributes to insulin-regulated gene expression. Journal of Biological Chemistry 276(11): 8507-8515, 2001

Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice. Journal of Endocrinology 173(1): 81-94, 2002

Role for sterol regulatory element binding protein-1c activation in mediating skeletal muscle insulin resistance via repression of rat insulin receptor substrate-1 transcription. Diabetologia 57(3): 592-602, 2014

Mice lacking CCAAT/enhancer-binding protein-α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs. Cell and Tissue Research 306(1): 57-63, 2001

Mice lacking CCAAT/enhancer binding protein alpha have increased alveolar epithelial cell proliferation and surfactant protein mRNAs. Molecular Biology of the Cell 12(Suppl.): 228a, 2001

Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis. Endocrinology 147(7): 3547-3554, 2006

Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein delta. Proceedings of the National Academy of Sciences of the United States of America 95(18): 10908-10913, 1998

A nucleoprotein complex containing CCAAT/enhancer-binding protein b interacts with an insulin response sequence in the insulin-like growth factor-binding protein-1 gene and contributes to insulin-regulated gene expression. The Journal of Biological Chemistry 276(11): 07-15, 2001

Mice lacking CCAAt/enhancer-binding protein-alpha show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs. Cell and Tissue Research 306(1): 57-63, 2001

Impaired water-maze performance in mice lacking transcription factor CCAAT/enhancer-binding protein beta. Neuroscience Research Communications 26(1): 59-67, 2000

Influence of alcohol on insulin sensitivity and insulin receptor substrate-1 mRNA expression in rat skeletal muscle. Zhonghua Yu Fang Yi Xue Za Zhi 38(5): 335-338, 2004

Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta. Diabetes 44(3): 267-271, 1995

Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 and identification of insulin receptor substrate-2. Diabetic Medicine 13(9 Suppl 6): S103-S108, 1996

Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise. Metabolism: Clinical and Experimental 55(8): 1046-1052, 2006

Insulin resistance in mice lacking neuronal nitric oxide synthase is not related to defective insulin stimulation of substrate delivery or glucose uptake in skeletal muscle a possible role for sympathetic overactivity ?. FASEB Journal 18(4-5): Abst 824 1, 2004