Disease relevance of Insig1

• Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats [1].
• Insulin-induced reactivation of an inactive herpes simplex thymidine kinase gene [2].
• In the present studies, we investigated whether insulin-induced HIF-1alpha expression is a prerequisite for insulin to induce other trophic effects in MiaPaCa2 human pancreatic cancer cells and whether inhibition of HIF-1alpha expression would decrease tumor glycolysis and improve host energy homeostasis [3].
• Insulin-induced activation of G3PAT was also blocked by pretreatment of intact myocytes with pertussis toxin and by prior addition, to homogenates, of an antiserum that recognizes the C-terminal decapeptide of Gi alpha.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Insulin induced Krebs II ascites cells to attach to the substratum and to adopt a flattened morphology associated with normal adhesion and movement [5].

High impact information on Insig1

• Insulin induced the release of adenosine trisphosphate (ATP), adenosine, and serotonin from platelet-dense granules in a NO-dependent manner [6].
• Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin [7].
• We produced mice with germline disruption of the Insig2 gene and Cre-mediated disruption of the Insig1 gene in liver [8].
• Schoenheimer effect explained--feedback regulation of cholesterol synthesis in mice mediated by Insig proteins [8].
• In cultured cells, Insig proteins are required for sterol-mediated inhibition of the processing of sterol regulatory element-binding proteins (SREBPs) to their nuclear forms [8].

Biological context of Insig1

• These findings suggest that the regulation of Insig-1 by PPARgamma agonists could in turn regulate SREBP processing and thus couple insulin sensitizers with the regulation of lipid homeostasis [9].
• Furthermore, a PPARgamma antagonist repressed the transactivation of the INSIG-1 promoter-reporter construct [9].
• Insulin-induced Akt1 and Akt2 phosphorylation was reduced in myotubes treated with siIRS-1, but only Akt2 phosphorylation was reduced in myotubes treated with siIRS-2 [10].
• Insulin-induced adipocyte differentiation. Activation of CREB rescues adipogenesis from the arrest caused by inhibition of prenylation [11].
• Betaine feeding prevented partially the alcohol-induced changes of hepatic lipids and injury in both genotypes. mRNA of Insig-1 was reduced in both genotypes fed alcohol [12].

Anatomical context of Insig1

• Insig-1 and -2 are closely related proteins of the endoplasmic reticulum (ER) that block proteolytic activation of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate the synthesis of cholesterol and fatty acids in liver and other organs [13].
• Insig-1 was identified as a PPARgamma target gene using microarray analysis of mRNA from the white adipose tissue of diabetic (db/db) animals treated with PPARgamma agonists [9].
• Insulin induced a marked glycogen synthase activity in wild-type and heterozygous primary hepatocytes; interestingly, this response was absent in IRS-2(-/-) cells but was rescued by infection with adenoviral IRS-2 [14].
• In differentiating 3T3-L1 cells, insig-1 and -2 rose in parallel with aP2 mRNA during differentiation [15].
• Transfection of mouse or human insig-1 into 3T3-L1 preadipocytes completely prevented oil red O staining and blocked upregulation of aP2, peroxisome proliferator-activated receptor gamma2, and carbohydrate response element-binding protein, while reducing down-regulation of preadipocyte factor 1 [15].

Associations of Insig1 with chemical compounds

• We demonstrated that Insig-1 is regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) providing a link between insulin sensitization/glucose homeostasis and lipid homeostasis [9].
• Insig-1 was induced in subcutaneous (9-fold) and epididymal (4-fold) fat pads from db/db mice treated for 8 days with the PPARgamma agonist rosiglitazone (30 mg/kg/day) [9].
• Insulin-induced tyrosine autophosphorylation of the IR beta-chain was augmented in IGF-IR--deficient cells [16].
• Insulin-induced p21ras activation does not require protein kinase C, but a protein sensitive to phenylarsine oxide [17].
• Insulin-induced receptor down-regulation was abolished after 12 h of dexamethasone treatment, when the intracellular receptor level was elevated [18].

Regulatory relationships of Insig1

• Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K [19].

Other interactions of Insig1

• Insulin-induced protein synthesis was both wortmannin sensitive and insensitive in wild-type and IRS-1 deficient mice [20].
• Insulin induced a strong, rapid (within 2 h) but transient fivefold increase in leptin mRNA levels [21].
• Insulin-induced accumulation of p21 mRNA and protein was inhibited by the addition of U0126 and SB203580 [22].
• Insulin-induced tyrosine phosphorylation of a M(r) 70,000 protein revealed by association with the Src homology 2 (SH2) and SH3 domains of p120GAP and Grb2 [23].
• Insulin-induced receptor internalization was dependent upon cellular energy production, protein synthesis, and endocytosis, but was insensitive to agents which primarily affect lysosomal, cytoskeletal, or transglutaminase activities [24].

Analytical, diagnostic and therapeutic context of Insig1

• Insulin induced in organ culture of a mouse mammary adenocarcinoma the expression of two cytoplasmic proteins of molecular size 72 and 49 kD [25].

References