scholarly journals Association of Variants in the Sterol Regulatory Element-Binding Factor 1 (SREBF1) Gene With Type 2 Diabetes, Glycemia, and Insulin Resistance: A Study of 15,734 Danish Subjects

Diabetes ◽  
2008 ◽  
Vol 57 (4) ◽  
pp. 1136-1142 ◽  
Author(s):  
N. Grarup ◽  
K. L. Stender-Petersen ◽  
E. A. Andersson ◽  
T. Jorgensen ◽  
K. Borch-Johnsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Regulatory Element ◽  
Binding Factor ◽  
Sterol Regulatory Element ◽  
Srebf1 Gene

scholarly journals Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes

Diabetologia ◽  
2006 ◽  
Vol 49 (11) ◽  
pp. 2642-2648 ◽  
Author(s):  
A.-H. Harding ◽  
R. J. F. Loos ◽  
J. Luan ◽  
S. O’Rahilly ◽  
N. J. Wareham ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regulatory Element ◽  
Gene Encoding ◽  
Binding Factor ◽  
Sterol Regulatory Element

Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus

2009 ◽  
Vol 29 (5) ◽  
pp. 283-292 ◽  
Author(s):  
Ali Ben Djoudi Ouadda ◽  
Emile Levy ◽  
Ehud Ziv ◽  
Geneviève Lalonde ◽  
Alain T. Sané ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Protein Expression ◽  
Body Weight Gain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mrna Levels ◽  
Psammomys Obesus ◽  
Element Binding Protein

AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKα-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKα to total AMPKα; (v) a stimulation in ACC activity despite increased AMPKα phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.

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