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INS — SREBF1

Pathways - manually collected, often from reviews:

• WikiPathways White fat cell differentiation: INS → SREBF1 (activation)

Text-mined interactions from Literome

Foretz et al., Mol Cell Biol 1999 : We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability
Fleischmann et al., Biochem J 2000 : Thus acute activation of PKB is sufficient to induce SREBP1 mRNA accumulation in primary hepatocytes, and might be the major signalling event by which insulin induces SREBP1 gene expression in the liver
Hasty et al., J Biol Chem 2000 : 5 to 25 mm and are also regulated by insulin , with the amount of insulin in the fetal bovine serum being sufficient for maximal stimulation of SREBP-1 expression
Xu et al., J Biol Chem 2001 : Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA
Lacasa et al., J Biol Chem 2001 : Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c ( adipocyte determination and differentiation 1/sterol regulatory element binding protein 1c ), through insulin mediated stimulation of ADD1/SREBP1c expression
Palmer et al., Biochem Biophys Res Commun 2002 : In hepatocytes, insulin stimulates a rapid increase in transcription of SREBP-1c and the appearance of the SREBP-1c protein in the nucleus
Botolin et al., J Biol Chem 2003 : In adult animals, insulin and oxysterols induce SREBP-1c gene transcription, whereas polyunsaturated fatty acids suppress the nuclear content of SREBP-1c through pre-translational regulatory mechanisms
Yang et al., Exp Cell Res 2003 (Breast Neoplasms) : SREBP-1c expression is induced in liver and adipose tissue by insulin and by fasting/refeeding and is critical for nutritional regulation of lipogenic gene expression
Matsumoto et al., J Clin Invest 2003 : PKClambda in liver mediates insulin induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity ... Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant negative form of PKClambda and was mimicked by overexpression of WT PKClambda
Ribaux et al., Biochem J 2003 : This resulted in the inhibition of insulin dependent increases in GCK and SREBP1 mRNAs ... The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin dependent induction of GCK and SREBP1
Diraison et al., Biochem J 2004 : In the present study, we determine whether over-expression in rat islets of the lipogenic transcription factor SREBP1c ( sterol-regulatory-element binding protein-1c ) affects insulin release, and whether changes in islet lipid content may be reversed by activation of AMPK ( AMP activated protein kinase )
Koistinen et al., Obes Res 2004 (Diabetes Mellitus, Type 2) : Our results provide evidence that insulin action on SREBP-1c is dysregulated in adipose tissue from type 2 diabetic subjects
Sekar et al., Am J Physiol Endocrinol Metab 2004 : Involvement of Sp1 and SREBP-1a in transcriptional activation of the LDL receptor gene by insulin and LH in cultured porcine granulosa-luteal cells
Kim et al., J Biol Chem 2004 : SREBP-1c could bind to these SREs and activate the LGK promoter, and insulin activated the LGK promoter in Alexander cells ... Insulin selectively increased SREBP-1c and LGK expression in primary hepatocytes
Nagata et al., J Biol Chem 2004 (Genetic Predisposition to Disease) : In hepatocytes from CBA/JN, the activity of CBA-SREBP-1c promoter was significantly increased by 2.4- and 2.2-fold, in response to 30 mm fructose or 10 nm insulin , respectively, whereas the activity of DBA-SREBP-1c promoter responded to insulin but not to fructose ... In hepatocytes from DBA/2N, both types of SREBP-1c promoter activities in response to insulin were attenuated
Louveau et al., J Endocrinol 2004 : No change in SREBP-1 mRNA levels was observed in response to GH and/or insulin
Nadeau et al., J Biol Chem 2004 (Insulin Resistance...) : Expression of SREBP-1 is enhanced by insulin ; however, the actual insulin signaling cascades employed are yet unclear ... We determined the roles of the phosphatidylinositol (PI) 3-kinase and mitogen activated protein ( MAP ) kinase dependent pathways in the effect of mediating insulin on SREBP-1 in L-6 skeletal muscle cells and 3T3 L1 adipocytes, using wortmannin or LY294002 to inhibit the PI 3-kinase pathway, and PD98059 to inhibit the MAP kinase dependent pathway ... In myocytes, insulin increased SREBP-1 protein in a dose dependent manner ... 1 and 10 nm insulin significantly increased expression of total cellular SREBP-1 protein at 24 and 48 h, nuclear SREBP-1 protein at 24 h, and SREBP-1a mRNA at 24 h ... Transfection of a dominant negative mutant of Ras similarly blocked the insulin effect on SREBP-1 ... In contrast, in adipocytes, the insulin effect on SREBP-1 was mediated via the PI 3-kinase and not the MAP kinase pathway ... In conclusion, although insulin increases skeletal muscle SREBP-1 expression in a dose dependent fashion via the MAP kinase dependent signaling pathway, insulin action on adipocyte SREBP-1 is mediated via the PI 3-kinase signaling pathway
Chen et al., Proc Natl Acad Sci U S A 2004 : Central role for liver X receptor in insulin mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver ... We conclude that insulin activates the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly through production of a ligand that activates LXRs or their heterodimerizing partner, the retinoid X receptor
Cagen et al., Biochem J 2005 : Insulin increases the expression of the SREBP-1c gene in intact liver and in hepatocytes cultured in vitro ... We have found that each of these sites is required for the full stimulatory response of the SREBP-1c promoter to insulin ... Ectopic expression of LXRalpha or SREBP-1c increased activity of the SREBP-1c promoter, and this effect is further enhanced by insulin ... The Sp1 and NF-Y sites adjacent to the SRE are also required for full activation of the SREBP-1c promoter by insulin
Deng et al., Endocrinology 2004 (Body Weight...) : Induction of SREBP-1c by insulin is dependent on liver x receptor (LXR)alpha
Iynedjian et al., Biochem J 2005 : The induction by insulin of the mRNAs encoding glucokinase and SREBF1 ( sterol-regulatory-element binding factor 1 ) were also normal in TRB3/NIPK hepatocytes
Bobard et al., J Biol Chem 2005 : Studies have shown that SREBP-1c expression is dependent on insulin but also on the availability of oxysterols, ligands of the nuclear liver X receptor ( LXR )
Datta et al., J Biol Chem 2005 : In addition, the results support a model where changes in SREBP-1c protein expression that occur in response to insulin signaling and liver X receptor signaling would be predicted to increase or decrease overall SREBP activity in a tissue-specific fashion depending on the initial fractional contribution of SREBP-1c to total cellular levels of SREBP
Eberlé et al., Biochimie 2004 : In vivo studies using transgenic and knockout mice suggest that SREBP-1c is involved in FA synthesis and insulin induced glucose metabolism ( particularly in lipogenesis ), whereas SREBP-2 is relatively specific to cholesterol synthesis
Hegarty et al., Proc Natl Acad Sci U S A 2005 : Both insulin and liver X receptor alpha ( LXRalpha ) induce SREBP-1c transcription ; however, the respective roles of these factors and the mechanism responsible for proteolytic cleavage of this SREBP isoform are not known
Takahashi et al., Diabetes 2005 (Glucose Intolerance...) : beta-Cell-specific expression of SREBP-1c caused reduction in islet mass and impaired glucose stimulated insulin secretion and was associated with accumulation of triglycerides, suppression of pancreas duodenal homeobox-1, and upregulation of uncoupling protein 2 gene expression
Kuriyama et al., Cell Metab 2005 (Body Weight) : This response is mediated by an insulin dependent increase in adipocyte SREBP-1c and its target mRNAs
Amemiya-Kudo et al., J Biol Chem 2005 : Promoter analyses of rat insulin I gene in non-beta cells revealed that nuclear SREBP-1c activates the insulin promoter through three novel SREBP binding sites ( SREs ), two of which overlap with E-boxes, binding sites for BETA2/E47 ... SREBP-1c mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low ... This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity
Wang et al., J Cell Sci 2005 (Diabetes Mellitus, Type 2) : Both high-glucose treatment and SREBP-1c activation in INS-1 cells resulted in lipid accumulation, impaired glucose stimulated insulin secretion, apoptosis, and strikingly similar gene expression patterns, including upregulation of lipogenic and pro-apoptotic genes and downregulation of IRS2, Bclxl and Pdx1
Achouri et al., Biochimie 2005 (Diabetes Mellitus, Experimental) : The dietary and SREBP-1c mediated insulin regulation of ACS-5 expression indicate that ACS-5 is involved in the anabolic fate of fatty acids
Nadeau et al., Am J Physiol Endocrinol Metab 2006 : SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction
Zitzer et al., Endocrinology 2006 (Glucose Intolerance...) : Down-regulation of SREBP-1 expression with the specific small interfering RNA blocked basal and LXRbeta induced expression of pancreatic duodenal homeobox 1 (PDX-1), insulin , and Glut2 genes ... These data support the role of LXRbeta, SREBP-1 , and cataplerosis/anaplerosis pathways in the control of insulin secretion in pancreatic beta-cells
Parton et al., Am J Physiol Endocrinol Metab 2006 (Body Weight...) : Limited role for SREBP-1c in defective glucose induced insulin secretion from Zucker diabetic fatty rat islets : a functional and gene profiling analysis ... However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model
Dif et al., Biochem J 2006 : In the present study, we aimed to decipher the mechanisms involved in the transcriptional effect of insulin on the SREBP-1c specific promoter of the human srebf-1 gene ... Furthermore, insulin increases the binding of SREBP-1 ( sterol-regulatory-element binding protein-1 ) to this promoter region in chromatin immunoprecipitation assay
Hansmannel et al., Biochem J 2006 : The transcription activator SREBP-1c ( sterol-regulatory-element binding protein-1c ) is induced by insulin in the liver and is considered a master regulator of lipogenic genes such as FASN ( fatty acid synthase ) ... Insulin and T0901317 triggered the accumulation of precursor and processed forms of SREBP-1c to similar levels and with comparable kinetics, and both effectors together caused synergistic increases in SREBP-1c protein levels
Li et al., J Biol Chem 2006 : Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes ... Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin ... We conclude that insulin has dual effects on human CYP7A1 gene transcription ; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c , which inhibits human CYP7A1 gene transcription
Yan et al., Arterioscler Thromb Vasc Biol 2007 (Carcinoma, Hepatocellular...) : Importantly, silencing of OSBP in hepatocytes suppressed the induction of SREBP1-c by insulin and resulted in a reduction of TG synthesis
Deng et al., J Biol Chem 2007 : SREBP-1c is directly regulated by insulin by transcriptional and post-transcriptional mechanisms ... Introduction of a small interfering RNA against Sp1 reduced both basal and insulin induced activation of the SREBP-1c promoter ... These studies identify a novel mechanism by which maximal activation of the rat SREBP-1c gene expression by insulin is mediated by Sp1 and its enhanced ability to interact with other transcriptional regulatory proteins
Boonsong et al., Biochem Soc Trans 2007 : Effect of exercise and insulin on SREBP-1c expression in human skeletal muscle : potential roles for the ERK1/2 and Akt signalling pathways
Roth et al., Pharmacogenet Genomics 2008 : Here we report that the activation of SREBP-1 by insulin or cholesterol in mouse liver and primary human hepatocytes inhibits the transcriptional effects in PXR and CAR
Kohjima et al., Int J Mol Med 2008 (Fatty Liver) : These data indicate that, in NAFLD, insulin signaling via IRS-1 causes the up-regulation of SREBP1-c , leading to the increased synthesis of fatty acids by the hepatocytes ; negative feedback regulation via AMPK does not occur and the activation of Foxa2, following a decrease of IRS-2, up-regulates fatty acid oxidation
Mauvoisin et al., Journal of cell communication and signaling 2007 : The latter binds both NF-Y and SREBP-1 transcription factors in response to insulin ... The most 3 ' IRE is localized between -372 and -297 bp and binds the NF-Y and SREBP-1 transcription factors in response to insulin
Park et al., Hepatology 2008 (Carcinoma, Hepatocellular...) : ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant negative AMPK partially prevented ALA induced suppression of insulin stimulated SREBP-1c expression
Qin et al., J Nutr Biochem 2009 (Insulin Resistance) : Taken together, our data suggest that the postprandial hypertriglycerides and the overproduction of apoB48 can be acutely inhibited by a CE by a mechanism involving improvements of insulin sensitivity of intestinal enterocytes and regulation of MTP and SREBP1c levels
Yellaturu et al., J Biol Chem 2009 : Furthermore, chemical and molecular inhibitors of the phosphoinositide 3-kinase pathway and its downstream kinase protein kinase B (PKB)/Akt prevented both insulin mediated phosphorylation of nascent SREBP-1c protein and its posttranslational processing
Sajan et al., J Lipid Res 2009 (Disease Models, Animal...) : In support of a critical mediatory role of aPKC, in both models, inhibition of hepatic aPKC by adenovirally mediated expression of kinase-inactive aPKC markedly diminished diet/insulin dependent activation of hepatic SREBP-1c and NFkappaB, and concomitantly improved hepatosteatosis, hypertriglyceridemia, hyperinsulinemia, and hyperglycemia
Del Mar Romero et al., Biosci Rep 2010 (Overweight) : In conclusion, the results presented suggest that the effect of OE on liver metabolism may be ( at least in part ) mediated through an insulin-sensitivity dependent modulation of the expression of SREBP-1c ( sterol-regulatory-element binding protein-1c ), resulting in the unique combined effect of mildly increased ( or maintained ) glucose disposal but also limited enhancement of lipogenesis
Palaniappan et al., Biol Reprod 2009 : Inhibition of the phosphatidylinositol 3-kinase pathway did not block the insulin induced increase in SREBF1a , whereas mitogen activated protein kinase inhibition reduced the insulin response
Kammoun et al., J Clin Invest 2009 (Fatty Liver...) : Hepatic lipogenesis depends on the insulin induced activation of the transcription factor SREBP-1c
Kim et al., J Biol Chem 2009 : LXRalpha increases SREBP-1c expression and then insulin stimulates the processing of the membrane bound precursor SREBP-1c protein, and it activates LGK expression through SREBP sites in its promoter
Han et al., J Exp Biol 2009 : Insulin at 200 nmol l ( -1 ) had an inhibiting effect on TG accumulation and the activity of ACC and FAS, but increased the gene expression of SREBP-1 , FAS and ACCalpha
Howell et al., Biochim Biophys Acta 2009 : N-3 polyunsaturated fatty acids suppress insulin induced SREBP-1c transcription via reduced trans activating capacity of LXRalpha ... We therefore examined the ability of n-3 PUFA to mitigate induction of SREBP-1c and its downstream lipogenic targets by insulin in primary rat hepatocyte cultures ... Insulin induced expression of SREBP-1c mRNA 5-6 fold as well as rat SREBP-1c promoter activity ... DHA effectively prevented LXRalpha dependent activation of both the wild type SREBP-1c promoter and the synthetic LXRE-driven promoter, and significantly blunted LXRalpha dependent activation of a Gal4-LXRalpha chimeric protein thus demonstrating that n-3 PUFA effectively mitigate induction of SREBP-1c by insulin via reduced trans-activation of LXRalpha
Suzuki et al., Endocrinology 2009 : RT-PCR analysis showed that insulin regulated expression of srebp1c , fas, glut4, and adiponectin is impaired in Uchl3 ( -/- ) cells
Elam et al., Metabolism 2010 (Insulin Resistance...) : Consistent with these findings, we found that the human SREBP-1c promoter was positively regulated by insulin and negatively regulated by STAT3
Taghibiglou et al., Nat Med 2009 (Brain Ischemia...) : The NMDAR mediated activation of SREBP-1 is a result of increased insulin induced gene-1 (Insig-1) degradation, which can be inhibited with an Insig-1 derived interference peptide ( Indip ) that we have developed
Li et al., Proc Natl Acad Sci U S A 2010 (Insulin Resistance) : In contrast, subnanomolar concentrations of rapamycin, an inhibitor of the mTORC1 kinase, blocked insulin induction of SREBP-1c , but had no effect on insulin suppression of PEPCK ... A specific inhibitor of S6 kinase, a downstream target of mTORC1, did not block insulin induction of SREBP-1c , suggesting a downstream pathway distinct from S6 kinase
Yamamoto et al., J Lipid Res 2010 (Diabetes Mellitus, Experimental) : Although regulation of SREBP-1c is known to occur at the transcriptional level, the precise mechanism by which insulin signaling activates SREBP-1c promoter remains to be elucidated ... Here we show that protein kinase C beta (PKCbeta) is a key mediator of insulin mediated activation of hepatic SREBP-1c and its target lipogenic genes
Wang et al., Biochem J 2010 : Taken together, these results suggest that SREBP-1c directly mediates the effect of insulin on Cidea in hepatocytes and that Cidea, at least in part, mediates SREBP-1c dependent lipid accumulation
Dubuquoy et al., J Hepatol 2011 (Fatty Liver) : We show that in the mouse liver, adiponutrin/PNPLA3 gene expression is under the direct transcriptional control of ChREBP ( carbohydrate-response element binding protein ) and SREBP1c ( sterol regulatory element binding protein1c ) in response to glucose and insulin , respectively
Ning et al., Endocrinology 2011 (Hyperinsulinism...) : Knockdown of either the IRE1a or XBP1 gene by small interfering RNA prevented the insulin stimulated promoter activities of both SREBP-1 and FAS genes
Fernández-Alvarez et al., J Biol Chem 2011 : Serial deletion and mutation assays reveal that both SREBP ( SRE ) and LXR ( LXRE ) response elements are involved in SREBP1c transcription regulation mediated by insulin and cholesterol derivatives
Qiao et al., Hepatology 2011 : Furthermore, SREBP-1c mediated the insulin and liver X receptor agonist TO901317 dependent induction of PNPLA3 gene expression in hepatocytes
Ge et al., International journal of biological sciences 2011 : Berberine hydrochloride at 25 µM attenuated insulin suppressed Pck1 ( ZL/ZF cells ), and insulin induced Srebp-1c expression ( SD/ZL/ZF cells ), suggesting modulation of insulin action
Deng et al., J Biol Chem 2012 : Similarly, in primary hepatocytes, CA-FoxO1 suppressed SREBP1-c expression and inhibited basal and insulin induced SREBP-1c promoter activity
Kwan et al., J Gastroenterol 2013 (Colorectal Neoplasms) : Upregulation of SREBP1 and FAS expression by insulin rescued these cells from oridonin induced apoptosis
Owen et al., Proc Natl Acad Sci U S A 2012 : The data reveal that insulin mediated stimulation of SREBP-1c processing requires the mechanistic target of rapamycin complex 1 ( mTORC1 ), which also is required for insulin mediated SREBP-1c mRNA induction
Henkel et al., Lab Invest 2012 (Disease Models, Animal...) : PGE ( 2 ) attenuated the insulin dependent induction of SREBP-1c and its target genes glucokinase and fatty acid synthase
Ito et al., J Lipid Res 2013 (MAP Kinase Signaling System) : The JNK inhibitor SP600125 blocked insulin induced upregulation of SREBP-1c expression ... Small interfering RNA mediated depletion of JNK2 suppressed insulin induced nuclear accumulation of the active form of SREBP-1 protein and upregulation of SREBP-1c
Boden et al., Obesity (Silver Spring) 2013 : Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue ... To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects ... Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue ... These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins ... We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation
Streicher et al., J Biol Chem 1996 : SREBP-1 mediates activation of the low density lipoprotein receptor promoter by insulin and insulin-like growth factor-I