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

Abstract

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

Resistant starch manipulated hyperglycemia/hyperlipidemia and related genes expression in diabetic rats

“…Insig-1 and Insig-2 play important roles in glucose homeostasis [15], and the regulation of intracellular cholesterol and fat metabolism as well [16]. The significantly enhanced the expression of the two insulin-induced genes, especially Insig1 (2.58 ± 0.32-fold) found in this study, would be highly related to the improved lipids composition because of the RS intervention.…”

Four SNPs of insulin-induced gene 1 associated with growth and carcass traits in Qinchuan cattle in China

“…Experiments with siRNA suggest that Insig-1 is related to SREBP1c mediated regulation of phosphoenolpyruvate carboxykinase (PCK2) (Krapivner et al, 2007). Recent research suggests that variation in Insig-1 is unlikely to have a major effect on type 2 diabetes (Szopa et al, 2010).…”

Biochips for Regenerative Medicine: Real-time Stem Cell Continuous Monitoring as Inferred by High-Throughput Gene Analysis

“…In this context, on the basis of its in vivo role in metabolism regulation, the unexplored possibility that IGF-1 differential expression could results in changes in the metabolic state of embryonic stem cells should be investigated, the full list can be found in Online Resource 1. Furthermore, we retrieved an upregulation of Stc1, Per1, Per3, and Insig1 after mitogen withdrawal, for which a clear role in the regulation of the cell metabolism was indicated [32][33][34][35]. More generally, we identified subsets of genes in the extracellular region or space whose regulation in the two experimental conditions that we investigated could result in changes of detectable extracellular molecules (i.e., enzymes, and transporters for metabolites, proteins, polysaccharides as well as key detectable molecules such as hormones).…”