scholarly journals Role of Uncoupling Protein-2 Up-Regulation and Triglyceride Accumulation in Impaired Glucose-Stimulated Insulin Secretion in a β-Cell Lipotoxicity Model Overexpressing Sterol Regulatory Element-Binding Protein-1c

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3566-3577 ◽  
Author(s):  
Tokuyuki Yamashita ◽  
Kazuhiro Eto ◽  
Yukiko Okazaki ◽  
Shigeo Yamashita ◽  
Toshimasa Yamauchi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Uncoupling Protein ◽  
Regulatory Element ◽  
Uncoupling Protein 2 ◽  
Β Cell ◽  
Triglyceride Accumulation ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Glutathionylation State of Uncoupling Protein-2 and the Control of Glucose-stimulated Insulin Secretion

2012 ◽  
Vol 287 (47) ◽  
pp. 39673-39685 ◽  
Author(s):  
Ryan J. Mailloux ◽  
Accalia Fu ◽  
Christine Robson-Doucette ◽  
Emma M. Allister ◽  
Michael B. Wheeler ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Glucose Stimulated Insulin Secretion

Corrigendum to “Reversion of hepatic steatosis by exercise training in obese mice: The role of sterol regulatory element-binding protein-1c” [Life Sci. 91(11–12) (2012) 395–401]

Life Sciences ◽  
2016 ◽  
Vol 152 ◽  
pp. 178-179
Author(s):  
Dennys E. Cintra ◽  
Eduardo R. Ropelle ◽  
Marcelo F. Vitto ◽  
Thais F. Luciano ◽  
Daniela R. Souza ◽  
...  
Keyword(s):  
Exercise Training ◽  
Hepatic Steatosis ◽  
Binding Protein ◽  
Regulatory Element ◽  
Obese Mice ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP

2016 ◽  
Vol 113 (38) ◽  
pp. E5685-E5693 ◽  
Author(s):  
Masami Shimizu-Albergine ◽  
Brian Van Yserloo ◽  
Martin G. Golkowski ◽  
Shao-En Ong ◽  
Joseph A. Beavo ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Leydig Cells ◽  
De Novo ◽  
Regulatory Element ◽  
De Novo Synthesis ◽  
Intracellular Lipid ◽  
Element Binding Protein ◽  
Short Palindromic Repeat ◽  
Sterol Regulatory Element

Luteinizing hormone (LH) stimulates steroidogenesis largely through a surge in cyclic AMP (cAMP). Steroidogenic rates are also critically dependent on the availability of cholesterol at mitochondrial sites of synthesis. This cholesterol is provided by cellular uptake of lipoproteins, mobilization of intracellular lipid, and de novo synthesis. Whether and how these pathways are coordinated by cAMP are poorly understood. Recent phosphoproteomic analyses of cAMP-dependent phosphorylation sites in MA10 Leydig cells suggested that cAMP regulates multiple steps in these processes, including activation of the SCAP/SREBP pathway. SCAP [sterol-regulatory element-binding protein (SREBP) cleavage-activating protein] acts as a cholesterol sensor responsible for regulating intracellular cholesterol balance. Its role in cAMP-mediated control of steroidogenesis has not been explored. We used two CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR associated protein 9) knockout approaches to test the role of SCAP in steroidogenesis. Our results demonstrate that SCAP is required for progesterone production induced by concurrent inhibition of the cAMP phosphodiesterases PDE4 and PDE8. These inhibitors increased SCAP phosphorylation, SREBP2 activation, and subsequent expression of cholesterol biosynthetic genes, whereas SCAP deficiency largely prevented these effects. Reexpression of SCAP in SCAP-deficient cells restored SREBP2 protein expression and partially restored steroidogenic responses, confirming the requirement of SCAP–SREBP2 in steroidogenesis. Inhibitors of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and isoprenylation attenuated, whereas exogenously provided cholesterol augmented, PDE inhibitor-induced steroidogenesis, suggesting that the cholesterol substrate needed for steroidogenesis is provided by both de novo synthesis and isoprenylation-dependent mechanisms. Overall, these results demonstrate a novel role for LH/cAMP in SCAP/SREBP activation and subsequent regulation of steroidogenesis.

The Potential Role of Sterol Regulatory Element Binding Protein Transcription Factors in Renal Injury

2007 ◽  
Vol 17 (1) ◽  
pp. 62-65 ◽  
Author(s):  
Marek Szolkiewicz ◽  
Michal Chmielewski ◽  
Anna Nogalska ◽  
Ewa Stelmanska ◽  
Julian Swierczynski ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Renal Injury ◽  
Potential Role ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Protein Transcription

Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis

2006 ◽  
Vol 291 (5) ◽  
pp. E982-E994 ◽  
Author(s):  
Laura E. Parton ◽  
Patrick J. McMillen ◽  
Yingnian Shen ◽  
Elizabeth Docherty ◽  
Erin Sharpe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Regulatory Element ◽  
Dominant Negative ◽  
Gene Profiling ◽  
Rat Islets ◽  
Zdf Rat ◽  
Element Binding Protein ◽  
Basal Insulin Secretion ◽  
Glucose Stimulated Insulin Secretion

Accumulation of intracellular lipid may contribute to defective insulin secretion in type 2 diabetes. Although Zucker diabetic fatty (ZDF; fa/fa) rat islets are fat-laden and overexpress the lipogenic master gene, sterol regulatory element binding protein 1c (SREBP-1c), the contribution of SREBP-1c to the secretory defects observed in this model remains unclear. Here we compare the gene expression profile of lean control ( fa/+) and ZDF rat islets in the absence or presence of dominant-negative SREBP-1c (SREBP-1c DN). ZDF islets displayed elevated basal insulin secretion at 3 mmol/l glucose but a severely depressed response to 17 mmol/l glucose. While SREBP-1c DN reduced basal insulin secretion from ZDF islets, glucose-stimulated insulin secretion was not improved. Of 57 genes differentially regulated in ZDF islets and implicated in glucose metabolism, vesicle trafficking, ion fluxes, and/or exocytosis, 21 were upregulated and 5 were suppressed by SREBP-1c DN. Genes underrepresented in ZDF islets were either unaffected ( Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca2+ channel subunit α1D, CPT2, SUR2, rab9, syt13), or inhibited ( syntaxin 7, secretogranin-2) by SREBP-1c inhibition. Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1α (HNF1α), HNF3β/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets. We conclude that upregulation of SREBP-1c and mild increases in triglyceride content do not explain defective glucose-stimulated insulin secretion from ZDF rats. However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model.

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