Genetic obesity increases pancreatic expression of mitochondrial proteins which regulate cholesterol efflux in BRIN-BD11 insulinoma cells

Bioscience Reports
Anna-Maria CaridisAnnette Graham

Abstract

Pancreatic β-cells are sensitive to fluctuations in cholesterol content, which can damage the insulin secretion pathway, contributing to the aetiology of type 2 diabetes mellitus. Cholesterol efflux to (apo)lipoproteins, via ATP-binding cassette (ABC) transporter A1 (ABCA1), can prevent intracellular cholesterol accumulation; in some peripheral cells, ABCA1-dependent efflux is enhanced by promotion of cholesterol trafficking to, and generation of Liver X receptor (LXR) ligands by, mitochondrial sterol 27-hydroxylase (Cyp27A1 (cytochrome P450 27 A1/sterol 27-hydroxylase)) and its redox partners, adrenodoxin (ADX) and ADX reductase (ADXR). Despite this, the roles of mitochondrial cholesterol trafficking (steroidogenic acute regulatory protein [StAR] and 18-kDa translocator protein [TSPO]) and metabolising proteins in insulin-secreting cells remain wholly uncharacterised. Here, we demonstrate an increase in pancreatic expression of Cyp27A1, ADXR, TSPO and LXRα, but not ADX or StAR, in obese (fa/fa) rodents compared with lean (Fa/?) controls. Overexpression of Cyp27A1 alone in BRIN-BD11 cells increased INS2 expression, without affecting lipid metabolism; however, after exposure to low-density lipoprotein (LDL), cholesterol efflux t...Continue Reading

References

Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M X ZuberM R Waterman
Feb 4, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·N H McClenaghan, P R Flatt
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·A T RemaleyH B Brewer
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J KluckenG Schmitz
Aug 16, 2001·The Journal of Biological Chemistry·X FuE G Lund
Jul 26, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Robert C Tuckey, Madeleine J Headlam
Jan 18, 2003·The Journal of Biological Chemistry·Genevieve EscherDmitri Sviridov
Feb 21, 2003·The Journal of Biological Chemistry·Marc-Estienne RoehrichGérard Waeber
Feb 25, 2003·The Biochemical Journal·Zufan ArayaKjell Wikvall
Aug 4, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yvonne LangeTheodore L Steck
Sep 24, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shunlin RenWilliam M Pandak
Oct 30, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Jenny WongAndrew J Brown
Jul 4, 2006·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·G N GallusA Federico
Aug 30, 2008·The International Journal of Biochemistry & Cell Biology·Andrew J Brown
Sep 27, 2008·Biochimica Et Biophysica Acta·Wanjin TangKjell Wikvall
Jul 4, 2009·Molecular Endocrinology·Jannick PétremandGérard Waeber
May 15, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Michelle A FryirsKerry-Anne Rye
Jun 10, 2010·The Journal of Clinical Investigation·Jeffrey M SturekCatherine C Hedrick
Jan 25, 2012·Nature Reviews. Endocrinology·Brian G DrewBronwyn A Kingwell
May 9, 2012·PloS One·Sabine RuttiMarc Y Donath

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding
ELISA

Software Mentioned

Image Studio

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.