scholarly journals Genetic Variants in Human Sterol Regulatory Element Binding Protein-1c in Syndromes of Severe Insulin Resistance and Type 2 Diabetes

Diabetes ◽  
2004 ◽  
Vol 53 (3) ◽  
pp. 842-846 ◽  
Author(s):  
M. Laudes ◽  
I. Barroso ◽  
J.'a. Luan ◽  
M. A. Soos ◽  
G. Yeo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Genetic Variants ◽  
Binding Protein ◽  
Regulatory Element ◽  
Severe Insulin Resistance ◽  
Element Binding Protein ◽  
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.

scholarly journals Absence of Sterol Regulatory Element-binding Protein-1 (SREBP-1) Ameliorates Fatty Livers but Not Obesity or Insulin Resistance inLepob/LepobMice

2002 ◽  
Vol 277 (22) ◽  
pp. 19353-19357 ◽  
Author(s):  
Naoya Yahagi ◽  
Hitoshi Shimano ◽  
Alyssa H. Hasty ◽  
Takashi Matsuzaka ◽  
Tomohiro Ide ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Fatty Livers ◽  
Sterol Regulatory Element

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 The Gene-Gene Interaction of INSIG-SCAP-SREBP Pathway on the Risk of Obesity in Chinese Children

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Fang-Hong Liu ◽  
Jie-Yun Song ◽  
Xiao-Rui Shang ◽  
Xiang-Rui Meng ◽  
Jun Ma ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Protein Gene ◽  
Risk Group ◽  
Binding Protein ◽  
Regulatory Element ◽  
Chinese Children ◽  
Increased Risk ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Binding Protein Gene

Background.Childhood obesity has become a global public health problem in recent years. This study aimed to explore the association of genetic variants in INSIG-SCAP-SREBP pathway with obesity in Chinese children.Methods.A case-control study was conducted, including 705 obese cases and 1,325 nonobese controls. We genotyped 15 single nucleotide polymorphisms (SNPs) of five genes in INSIG-SCAP-SREBP pathway, including insulin induced gene 1 (INSIG1), insulin induced gene 2 (INSIG2), SREBP cleavage-activating protein gene (SCAP), sterol regulatory element binding protein gene 1 (SREBP1), and sterol regulatory element binding protein gene 2 (SREBP2). We used generalized multifactor dimensionality reduction (GMDR) and logistic regression to investigate gene-gene interactions.Results.Single polymorphism analyses showed thatSCAPrs12487736 and rs12490383 were nominally associated with obesity. We identified a 3-locus interaction on obesity in GMDR analyses(P=0.001), involving 3 genetic variants ofINSIG2,SCAP,andSREBP2. The individuals in high-risk group of the 3-locus combinations had a 79.9% increased risk of obesity compared with those in low-risk group (OR=1.799, 95% CI: 1.475–2.193,P=6.61×10-9).Conclusion.We identified interaction of three genes in INSIG-SCAP-SREBP pathway on risk of obesity, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect.

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