Stimulation of Acetyl-CoA Carboxylase Gene Expression by Glucose Requires Insulin Release and Sterol Regulatory Element Binding Protein 1c in Pancreatic MIN6  -Cells

Diabetes ◽  
2002 ◽  
Vol 51 (8) ◽  
pp. 2536-2545 ◽  
Author(s):  
C. Andreolas ◽  
G. da Silva Xavier ◽  
F. Diraison ◽  
C. Zhao ◽  
A. Varadi ◽  
...  
2003 ◽  
Vol 278 (31) ◽  
pp. 28410-28417 ◽  
Author(s):  
So-Young Oh ◽  
Sahng-Kyoo Park ◽  
Jae-Woo Kim ◽  
Yong-Ho Ahn ◽  
Sahng-Wook Park ◽  
...  

2003 ◽  
Vol 376 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Pascale G. RIBAUX ◽  
Patrick B. IYNEDJIAN

Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem. J. 351, 621–627; Fleischmann and Iynedjian (2000) Biochem. J. 349, 13–17]. The objective of the present study was to determine whether activation of PKB during insulin stimulation of hepatocytes was a necessary condition for the induction of the two genes. Activation of PKB by insulin was inhibited by pretreatment of the hepatocytes with C2 ceramide. This resulted in the inhibition of insulin-dependent increases in GCK and SREBP1 mRNAs. A triple mutant of PKB failed to interfere with insulin activation of PKB in hepatocytes even at high overexpression levels achieved after adenovirus transduction. A PKB–CaaX fusion protein, which can act as a dominant-negative inhibitor of PKB activation in other cells, was shown to be constitutively activated in hepatocytes and to trigger insulin-like induction of GCK and SREBP1. In addition, constitutive PKB–CaaX activity caused refractoriness of the hepatocytes to insulin signalling at an upstream step resulting in the inhibition of both extracellular-signal-regulated kinase 1/2 and endogenous PKB activation. The stimulation of gene expression by constitutively active PKB–CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1.


2007 ◽  
Vol 282 (29) ◽  
pp. 21090-21099 ◽  
Author(s):  
Norimasa Tamehiro ◽  
Yukari Shigemoto-Mogami ◽  
Tomoshi Kakeya ◽  
Kei-ichiro Okuhira ◽  
Kazuhiro Suzuki ◽  
...  

2015 ◽  
Vol 35 (2) ◽  
pp. 803-815 ◽  
Author(s):  
Andreas Bitter ◽  
Andreas K. Nüssler ◽  
Wolfgang E. Thasler ◽  
Kathrin Klein ◽  
Ulrich M. Zanger ◽  
...  

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.


2012 ◽  
Vol 287 (24) ◽  
pp. 20132-20143 ◽  
Author(s):  
Xiong Deng ◽  
Wenwei Zhang ◽  
InSug O-Sullivan ◽  
J. Bradley Williams ◽  
Qingming Dong ◽  
...  

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