Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls

Endocrine Journal

Volumn 61, Issue 2, 2014, Pages 111-117

  Heimark, Douglas ^a   McAllister, Jan ^b   Larner, Joseph ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Chiro Inositol; Epimerase; Myo Inositol; Polycystic ovary syndrome; Theca

Indexed keywords

EPIMERASE; INOSITOL;

ADULT; ANALYTICAL PARAMETERS; ARTICLE; CONTROLLED STUDY; DISEASE ASSOCIATION; ENZYME ACTIVITY; ENZYME REGULATION; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; INSULIN RESISTANCE; INSULIN SENSITIVITY; MYOINOSITOL TO CHIROINOSITOL RATIO; OVARY POLYCYSTIC DISEASE; THECA CELL;

ADULT; CARBOHYDRATE EPIMERASES; FEMALE; HUMANS; INOSITOL; INSULIN RESISTANCE; POLYCYSTIC OVARY SYNDROME; STEREOISOMERISM; THECA CELLS;

EID: 84896855238     PISSN: 09188959     EISSN: 13484540     Source Type: Journal    
DOI: 10.1507/endocrj.EJ13-0423     Document Type: Article

References (45)

1. Franks S, Gharani N, Waterworth D, Batty S, White D, et al. (1997) The genetic basis of polycystic ovary syndrome. Hum Reprod 12: 2641-2648.
2. Goldzieher J (1981) Polycystic ovarian disease. Fertil Steril 35: 371-394.
3. Barnes R, Rosenfield RL (1989) The polycystic ovary syndrome: pathogenesis and treatment. Ann Intern Med 110: 386-399.
4. Barnes RB, Rosenfield RL, Burstein S, Ehrmann DA (1989) Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N Engl J Med 320: 559-565.
5. Goldzeiher JW, Green JA (1962) The polycystic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab 22: 325-338.
6. Erickson GF, Magoffin DA, Dyer CA, Hofeditz C (1985) The ovarian androgen producing cells: a review of structure/function relationships. Endocr Rev 6: 371-399.
7. Larner J, Craig J (1996) Urinary myo-inositol-to-chiroinositol ratios and insulin resistance. Diabetes Care 19: 76-78.
8. Kennington A, Hill C, Craig J, Bogardus C, Raz I, et al. (1990) Low urinary chiro-inositol excretion in noninsulin-dependent diabetes mellitus. N Engl J Med 323: 373-378.
9. Asplin I, Galasko G, Larner J (1993) chiro-inositol deficiency and insulin resistance: a comparison of the chiroinositol-and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects. Proc Natl Acad Sci U S A 90: 5924-5928.
10. Suzuki S, Kawasaki H, Satoh Y, Ohtomo M, Hirai M, et al. (1994) Urinary chiro-inositol excretion is an index marker of insulin sensitivity in Japanese type II diabetes. Diabetes Care 17: 1465-1468.
11. Shashkin P, Shashkina E, Fernqvist-Forbes E, Zhou Y, Grill V, et al. (1997) Insulin mediators in man: effects of glucose ingestion and insulin resistance. Diabetologia 40: 557-563.
12. Baillargeon J-P, Iuorno MJ, Apridonidze T, Nestler JE (2010) Uncoupling Between Insulin and Release of a D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator of Insulin Action in Obese Women With Polycystic Ovary Syndrome. Metab Syndr Relat Disord 8: 127-136.
13. Scioscia M, Gumaa K, Kunjara S, Paine M, Selvaggi L, et al. (2006) Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and-2. J Clin Endocrinol Metab 91: 709-717.
14. Larner J, Price J, Heimark D, Smith L, Rule G, et al. (2003) Isolation, structure, synthesis, and bioactivity of a novel putative insulin mediator. A galactosamine chiro-inositol pseudo-disaccharide Mn2+ chelate with insulin-like activity. J Med Chem 46: 3283-3291.
15. Pak Y, Hong Y, Kim S, Piccariello T, Farese RV, et al. (1998) In vivo chiro-Inositol metabolism in the rat: A defect in chiro-Inositol synthesis from myo-Inositol and an increased incorporation of chiro-[3H]Inositol into phospholipid in the Goto-Kakizaki (G.K.) rat. Mol Cells 8: 301-309.
16. Sun T, Heimark D, Nguygen T, Nadler J, Larner J (2002) Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem Biophys Res Commun 293: 1092-1098.
17. McAllister J, Simpson E. Human theca interna cells in culture. Methods in Toxicology. 3. San Diego: Academic Press; 1993. p. 330-339.
18. Nelson VL, Legro RS, Strauss JF, McAllister JM (1999) Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 13: 946-957.
19. Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, Wood JR, Legro RS, et al. (2004) Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology 145: 799-808.
20. Wickenheisser JK, Quinn PG, Nelson VL, Legro RS, Strauss JF, et al. (2000) Differential activity of the cytochrome P450 17α-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells. J Clin Endocrinol Metab 85: 2304-2311.
21. Zawadzki J, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Hazeltine F, Merriam G, editors. Polycystic ovary syndrome Current issues in endocrinology and metabolism Boston: Blackwell. Boston: Blackwell Scientific; 1992. p. 377-384.
22. Legro RS, Driscoll D, Strauss III JF, Fox J, Dunaif A (1998) Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 95: 14956-14960.
23. Wickenheisser JK, Biegler JM, Nelson-DeGrave VL, Legro RS, Strauss JF, et al. (2012) Cholesterol Side-Chain Cleavage Gene Expression in Theca Cells: Augmented Transcriptional Regulation and mRNA Stability in Polycystic Ovary Syndrome. PLoS One 7: e48963.
24. Gilling-Smith C, Story H, Rogers V, Franks S (1997) Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin Endocrinol (Oxf) 47: 93-99.
25. Jakubowicz D, Nestler J (1997) 17 α-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome offer dietary weight loss. J Clin Endocrinol Metab 82: 556-560.
26. Nestler J (1998) Inositolphosphoglycans (IPGs) as mediators of insulin's steroidogenic actions. J Basic Clin Physiol Pharmacol 9: 197-204.
27. Nelson VL, Qin K, Rosenfield RL, Wood JR, Penning TM, et al. (2001) The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab 86: 5925-5933.
28. Daneshmand S, Weitsman SR, Navab A, Jakimiuk AJ, Magoffin DA (2002) Overexpression of theca-cell messenger RNA in polycystic ovary syndrome does not correlate with polymorphisms in the cholesterol side-chain cleavage and 17α-hydroxylase/C17-20 lyase promoters. Fertil Steril 77: 274-280.
29. Wickenheisser JK, Nelson-DeGrave VL, McAllister JM (2005) Dysregulation of cytochrome P450 17α-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J Clin Endocrinol Metab 90: 1720-1727.
30. Nestler JE, Jakubowicz DJ, Falcon de Vargas A, Brik C, Quintero N, et al. (1998) Insulin Stimulates Testosterone Biosynthesis by Human Thecal Cells from Women with Polycystic Ovary Syndrome by Activating Its Own Receptor and Using Inositolglycan Mediators as the Signal Transduction System. J Clin Endocrinol Metab 83: 2001-2005.
31. Alvarez JF, Varela I, Ruiz-Albusac JM, Mato JM (1988) Localisation of the insulin-sensitive phosphatidylinositol glycan at the outer surface of the cell membrane. Biochem Biophys Res Commun 152: 1455-1462.
32. Alvarez J, Sánchez-Arias J, Guadaño A, Estévez F, Varela I, et al. (1991) Transport in isolated rat hepatocytes of the phospho-oligosaccharide that mimics insulin action. Effects of adrenalectomy and glucocorticoid treatment. Biochem J 274 369-374.
33. Hans SK, Camara F, Altiti A, Martín-Montalvo A, Brautigan DL, et al. (2010) Synthesis of C-glycoside analogues of β-galactosamine-(1-->4)-3-O-methyl-Dchiro-inositol and assay as activator of protein phosphatases PDHP and PP2Cα. Bioorg Med Chem 18: 1103-1110.
34. Livingstone C, Collison M (2002) Sex steroids and insulin resistance. Clin Sci 102: 151-166.
35. Bhasin S (2003) Effects of Testosterone Administration on Fat Distribution, Insulin Sensitivity, and Atherosclerosis Progression. Clin Infect Dis 37: S142-S149.
36. Mårin P, Holmäng S, Jönsson L, Sjöström L, Kvist H, et al. (1992) The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 16: 991-997.
37. Diamanti-Kandarakis E, Dunaif A (2012) Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications. Endocr Rev 33: 981-1030.
38. Book C-B, Dunaif A (1999) Selective Insulin Resistance in the Polycystic Ovary Syndrome. J Clin Endocrinol Metab 84: 3110-3116.
39. Eriksen M, Pørneki AD, Skov V, Burns JS, Beck-Nielsen H, et al. (2010) Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS. PLoS One 5: e14469.
40. Carlomagno G, Unfer V, Roseff S (2011) The D-chiroinositol paradox in the ovary. Fertil Steril 95: 2515-2516.
41. Farese RV, Rosic N, Babischkin J, Farese MG, Foster R, et al. (1986) Dual activation of the inositol-triphosphate-calcium and cyclic nucleotide intracellular signaling systems by adrenocorticotropin in rat adrenal cells. Biochem Biophys Res Commun 135: 742-748.
42. York SJ, Armbruster BN, Greenwell P, Petes TD, York JD (2005) Inositol Diphosphate Signaling Regulates Telomere Length. J Biol Chem 280: 4264-4269.
43. Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, et al. (2010) Inositol Pyrophosphates Inhibit Akt Signaling, Thereby Regulating Insulin Sensitivity and Weight Gain. Cell 143: 897-910.
44. Brautigan D, Brown M, Grindrod S, Chinigo G, Kruszewski A, et al. (2005) Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action. Biochemistry 44: 11067-11073.
45. Lin X, Ma L, Gopalan C, Ostlund RE (2009) D-chiro-Inositol is absorbed but not synthesised in rodents. Br J Nutr 102: 1426-1434.