Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents β cell failure in rodent models of type 2 diabetes

Journal of Clinical Investigation

Volumn 121, Issue 8, 2011, Pages 3331-3342

  Tiano, Joseph P ^a   Delghingaro Augusto, Viviane ^b   Le May, Cedric ^a   Liu, Suhuan ^a   Kaw, Meenakshi K ^c   Khuder, Saja S ^c   Latour, Martin G ^b   Bhatt, Surabhi A ^a   Korach, Kenneth S ^d   Najjar, Sonia M ^c   Prentki, Marc ^b   Mauvais Jarvis, Franck ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

^c MEDICAL COLLEGE OF OHIO   (United States)

^d NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIACYLGLYCEROL; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FATTY ACID SYNTHASE; G PROTEIN COUPLED RECEPTOR 30; GLYCEROLIPID; MONOACYLGLYCEROL; PHOSPHOLIPID; STAT3 PROTEIN; TRIACYLGLYCEROL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL DIFFERENTIATION; CELL SURVIVAL; CONTROLLED STUDY; DETOXIFICATION; DOWN REGULATION; DRUG PELLET; ESTERIFICATION; ESTROGEN RESPONSIVE ELEMENT; FATTY ACID OXIDATION; FATTY ACID SYNTHESIS; FEMALE; HUMAN; HYPERGLYCEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIPID STORAGE; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS INSUFFICIENCY; PANCREAS ISLET BETA CELL; PANCREAS ISLET BETA CELL FAILURE; PANCREAS ISLET CELL FUNCTION; PRIORITY JOURNAL; RAT; ZUCKER DIABETIC FATTY RAT;

ANIMALS; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; FATTY ACID SYNTHETASE COMPLEX; GENE DELETION; HUMANS; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; LIPIDS; MALE; MICE; RATS; RATS, ZUCKER; RECEPTORS, ESTROGEN; STAT3 TRANSCRIPTION FACTOR;

EID: 79960977229     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI44564     Document Type: Article

References (45)

1. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116(7):1802-1812. (Pubitemid 44033300)
2. Liu S, Mauvais-Jarvis F. Minireview: Estrogenic protection of beta-cell failure in metabolic diseases. Endocrinology. 2010;151(3):859-864.
3. Le May C, et al. Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proc Natl Acad Sci U S A. 2006;103(24):9232-9237. (Pubitemid 43902561)
4. Liu S, et al. Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes. 2009;58(10):2292-2302.
5. Wong WP, et al. Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the insulin promoter and favors insulin synthesis. Proc Natl Acad Sci U S A. 2010;107(29):13057-13062.
6. Pick A, et al. Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes. 1998;47(3):358-364. (Pubitemid 28104196)
7. Mauvais-Jarvis F, et al. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. Diabetes. 2004;53(3):645-653. (Pubitemid 38270633)
8. Louet JF, et al. Gender and neurogenin3 influence the pathogenesis of ketosis-prone diabetes. Diabetes Obes Metab. 2008;10(10):912-920.
9. Gao Q, et al. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine. 2007;13(1):89-94. (Pubitemid 46067391)
10. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH. Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Proc Natl Acad Sci U S A. 1994;91(23):10878-10882.
11. Jonas JC, et al. Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem. 1999;274(20):14112-14121.
12. Nolan CJ, et al. Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia. 2006;49(9):2120-2130. (Pubitemid 44168480)
13. Delghingaro-Augusto V, et al. Islet beta cell failure in the 60% pancreatectomised obese hyperlipidaemic Zucker fatty rat: severe dysfunction with altered glycerolipid metabolism without steatosis or a falling beta cell mass. Diabetologia. 2009;52(6):1122-1132.
14. Kang L, et al. Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling. Mol Endocrinol. 2010;24(4):709-721.
15. Stauffer SR, et al. Pyrazole ligands: structure-affinity/ activity relationships and estrogen receptor-alpha-selective agonists. J Med Chem. 2000;43(26):4934-4947. (Pubitemid 32040974)
16. Bologa CG, et al. Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat Chem Biol. 2006;2(4):207-212.
17. Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor-beta potency-selective ligands: structureactivity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem. 2001;44(24):4230-4251. (Pubitemid 33095330)
18. Wakil SJ. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry. 1989;28(11):4523-4530. (Pubitemid 19151020)
19. Nilsson S, et al. Mechanisms of estrogen action. Physiol Rev. 2001;81(4):1535-1565. (Pubitemid 32951806)
20. Jakacka M, Ito M, Martinson F, Ishikawa T, Lee EJ, Jameson JL. An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. Mol Endocrinol. 2002;16(10):2188-2201. (Pubitemid 35155533)
21. Harrington WR, et al. Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action. Mol Endocrinol. 2006;20(3):491-502. (Pubitemid 43291204)
22. Chambliss KL, et al. Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice. J Clin Invest. 2010;120(7):2319-2330.
23. Inoue H, et al. Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo. Nat Med. 2004;10(2):168-174. (Pubitemid 38524887)
24. Ueki K, Kondo T, Tseng YH, Kahn CR. Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. Proc Natl Acad Sci U S A. 2004;101(28):10422- 10427. (Pubitemid 38924941)
25. Kinoshita S, et al. Role of hepatic STAT3 in the regulation of lipid metabolism. Kobe J Med Sci. 2008;54(4):E200-E208.
26. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet. 1996;14(1):95-97. (Pubitemid 26301554)
27. Lee JY, Hennighausen L. The transcription factor Stat3 is dispensable for pancreatic beta-cell development and function. Biochem Biophys Res Commun. 2005;334(3):764-768. (Pubitemid 41033187)
28. Griffen SC, Wang J, German MS. A genetic defect in beta-cell gene expression segregates independently from the fa locus in the ZDF rat. Diabetes. 2001;50(1):63-68. (Pubitemid 32047982)
29. Mauvais-Jarvis F. Estrogen and androgen receptors: regulators of fuel homeostasis and emerging targets for diabetes and obesity. Trends Endocrinol Metab. 2011;22(1):24-33.
30. Sreenan S, Sturis J, Pugh W, Burant CF, Polonsky KS. Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone. Am J Physiol. 1996;271(4 pt 1):E742-E747.
31. Pickavance LC, Brand CL, Wassermann K, Wilding JP. The dual PPARalpha/gamma agonist, ragaglitazar, improves insulin sensitivity and metabolic profile equally with pioglitazone in diabetic and dietary obese ZDF rats. Br J Pharmacol. 2005;144(3):308-316. (Pubitemid 40313676)
32. D'Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS. Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem. 2005;280(43):35983-35991. (Pubitemid 41633867)
33. Gao H, et al. Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol. 2006;20(6):1287-1299. (Pubitemid 43801232)
34. Buettner C, et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med. 2008;14(6):667-675. (Pubitemid 351809549)
35. Margolis KL, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004;47(7):1175-1187. (Pubitemid 39093314)
36. Kanaya AM, et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/ progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138(1):1-9. (Pubitemid 36232088)
37. Carr MC, et al. Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy. Diabetes Care. 2005;28(7):1555-1561. (Pubitemid 40923064)
38. Chadwick CC, et al. Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity. Proc Natl Acad Sci U S A. 2005;102(7):2543-2548. (Pubitemid 40279413)
39. Raz R, Lee CK, Cannizzaro LA, d'Eustachio P, Levy DE. Essential role of STAT3 for embryonic stem cell pluripotency. Proc Natl Acad Sci U S A. 1999;96(6):2846-2851. (Pubitemid 29148806)
40. Dupont S, Krust A, Gansmuller A, Dierich A, Chambon P, Mark M. Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development. 2000;127(19):4277-4291.
41. Wang C, et al. GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol. 2008;22(3):636-648. (Pubitemid 351397791)
42. Najjar SM, et al. Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab. 2005;2(1):43-53. (Pubitemid 43239824)
43. Hohmeier HE, Mulder H, Chen G, Henkel-Rieger R, Prentki M, Newgard CB. Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion. Diabetes. 2000;49(3):424-430. (Pubitemid 30131788)
44. Mauvais-Jarvis F, et al. Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest. 2002;109(1):141-149. (Pubitemid 34052550)
45. Cariou B, et al. Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin receptor knockout mice. Endocrinology. 2004;145(4):1926-1932. (Pubitemid 38402402)