Rosiglitazone Induction of Insig-1 in White Adipose Tissue Reveals a Novel Interplay of Peroxisome Proliferator-activated Receptor γ and Sterol Regulatory Element-binding Protein in the Regulation of Adipogenesis

Kast-Woelbern, Heidi R.; Dana, Sharon L.; Cesario, Rosemary M.; Sun, Li; Grandpre, Louise Y. de; Brooks, Mason E.; Osburn, Deborah L.; Reifel‐Miller, Anne; Klausing, Kay; Leibowitz, Mark D.

doi:10.1074/jbc.m403145200

Cited by 100 publications

(85 citation statements)

References 31 publications

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“…In the nucleus, the mature form of SREBP-1c is able to bind to specific sequences (sterol-regulatory elements SRE and E-boxes) located in the promoter gene of SREBP target genes (Figure 1.1). (Fig.1) (6). Considering that INSIG-1 appears to inhibit lipo-and adipogenesis, it is hard to reconcile this observation with the pro-adipogenic role of PPAR (9).…”

Section: Transcriptional Regulation Of Lipogenesis In Adipose Tissuementioning

confidence: 99%

Regulation of Lipogenic Genes in Obesity

Mandard

Kersten

2006

Nutritional Genomics

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Section: Transcriptional Regulation Of Lipogenesis In Adipose Tissuementioning

confidence: 99%

Regulation of Lipogenic Genes in Obesity

Mandard

Kersten

2006

Nutritional Genomics

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“…INSIG-1 is a central regulator in the processing of sterol regulatory element binding proteins. Two animal studies demonstrated an antilipogenic effect of INSIG-1 in vitro and in vivo (23) and identified INSIG-1 as a peroxisome proliferator-activated receptor ␥ target gene, providing a link between insulin sensitization and glucose homeostasis as well as lipid homeostasis (24).…”

mentioning

confidence: 99%

Genome-wide Linkage Scans for Fasting Glucose, Insulin, and Insulin Resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program

Freedman

Hanis

et al. 2005

Diabetes

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Genome-wide linkage analyses were performed using a multipoint variance components method in eight study groups from four multicenter networks (whites and blacks in GenNet; whites, blacks, and Mexican Americans in GENOA; whites and blacks in HyperGEN; and Asians in SAPPHIRe) that comprise the National Heart, Lung, and Blood Institute Family Blood Pressure Program (FBPP), in order to identify quantitative trait loci (QTLs) influencing fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). These study populations were enriched with subjects who had elevated blood pressure. Participants fasting <8 h, those with a history of type 2 diabetes, or those on antidiabetic medications were excluded from the current investigation. These three phenotypes were suitably transformed to approximate normal distributions. Each phenotype was adjusted for the effects of age, BMI, and field center separately by sex within each of the eight network ethnicity groups before genetic analysis. A total of 8,664 subjects comprising 5,923 sibpairs from 4,043 families with 365 markers were available for conducting a meta-analysis using a modified Fisher's method of combining the P values from each of the eight scans. Evidence of linkages was found on chromosome 7q36 at 163 cM, with a logarithm of odds (LOD) score of 3.21 for HOMA-IR, and on chromosome 19q13 at 88 cM, with a LOD score of 3.33 for fasting glucose. We also found suggestive linkages (LOD score >2.2) on chromosome 7q36 at 163 cM, with LOD scores of 2.31 for fasting glucose and 2.26 for fasting insulin (versus the LOD score of 3.21 for HOMA-IR at this locus). In conclusion, QTLs were identified on chromosomes 7q36 and 19q13 for fasting glucose, insulin, and insulin resistance in large and multiple-ethnicity populations in the FBPP with good replications across several other independent studies for relevant traits. Follow-up dense mapping and association studies are warranted. Diabetes 54:909 -914, 2005

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“…However, the proposed USF binding site is not highly homologous to established SREs or E-boxes. Moreover, an SRE was recently described [34] in the human INSIG1 promoter (located between −545 and −536, see Fig. 2a), but an equivalent SRE sequence does not seem to be conserved in the mouse Insig1 promoter.…”

Section: Discussionmentioning

confidence: 95%

Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration

et al. 2006

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Aims/hypothesis Insulin-induced gene 1 (INSIG1) is a protein that blocks proteolytic activation of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate genes regulating cholesterol and fatty acid metabolism and possibly genes involved in glucose homeostasis. In search of genetic regulation of these processes we examined human INSIG1 for common polymorphisms and analysed their associations with biochemical parameters related to lipid and glucose metabolism. Methods Associations between common polymorphisms in INSIG1 and several biochemical parameters were analysed in a group of 618 healthy, 50-year-old men. A replication analysis was performed in a cohort of 472 healthy, middleaged men. The impact of one promoter polymorphism on oral glucose tolerance was analysed in a subset of 181 subjects. Small interfering RNA (siRNA) inhibition was used to test the significance of INSIG1 for gene expression in human Huh7 hepatoma cells. Results A potentially functional polymorphism, a C to T substitution at position −169, was discovered in a highly conserved section of the promoter. Significant relationships between the −169C>T polymorphism and plasma glucose concentration were found in two cohorts of healthy, middleaged men (p<0.01 and p<0.02, respectively). The −169T allele was associated with significantly lower post-load plasma glucose concentrations. A significant (p=0. Diabetologia (2007) 50:94-102

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Rosiglitazone Induction of Insig-1 in White Adipose Tissue Reveals a Novel Interplay of Peroxisome Proliferator-activated Receptor γ and Sterol Regulatory Element-binding Protein in the Regulation of Adipogenesis

Abstract: Insulin-induced gene 1 (INSIG-1) is a key regulator in the processing of the sterol regulatory element-binding proteins (SREBPs). We demonstrated that

Cited by 100 publications

References 31 publications

Regulation of Lipogenic Genes in Obesity

Regulation of Lipogenic Genes in Obesity

Genome-wide Linkage Scans for Fasting Glucose, Insulin, and Insulin Resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program

Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration

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