Preventive Nutrition and Food Science

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Ovariectomy on Insulin Resistance and β-Cell Function and Mass

  • Choi, Soo-Bong (Department of Internal Medicine, Konkuk University) ;
  • Park, Chun-Hee (Department of Food Science and Nutrition, Hoseo University) ;
  • Jun, Dong-Wha (Department of Food Science and Nutrition, Hoseo University) ;
  • Jang, Jin-Sun (Department of Food Science and Nutrition, Hoseo University) ;
  • Park, Sun-Min (Department of Food Science and Nutrition, Hoseo University)
  • Published : 2004.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

The prevalence of type-2 diabetes increases remarkably in post-menopausal women, possibly because insulin secretion fails to compensate for the insulin resistance induced in various tissues by estrogen insufficiency. However, this has not been fully defined. Therefore, the present study investigated whether an ovariectomy (OVX) would increase insulin resistance and decrease the $\beta$-cell function and mass in female rats with and without a $90\%$ pancreatectomy (Px). Female rats aged 15 weeks were divided into four groups: 1) OVX + Px, 2) SOVX (sham operation of OVX) + Px, 3) OVX + SPx (sham operation of Px), and 4) SOVX + SPx, and given a $30\%$ fat diet for 8 weeks. At the end of the experimental period, the islet function and insulin resistance were determined using a hyperglycemic clamp and a euglycemic hyperinsulinemic clamp, respectively. The OVX only increased the body weight in the SPx rats, which was partially related to the food intake. Yet, the OVX did increase the peripheral insulin resistance, while the Px increased this resistance further. The OVX and Px both exacerbated the islet function, as measured by the insulin secretion pattern, while delaying and decreasing the first-phase insulin secretion. The OVX only decreased the proliferation of $\beta$-cells in the Px rats, while increasing apoptosis in both the Px and SPx rats. As a result, the OVX decreased the $\beta$-cell mass in the Px rats, but increased the mass in the SPx rats. In conclusion, an OVX was found to accelerate the development and progression of diabetes by increasing the insulin resistance and decreasing the $\beta$-cell mass. Therefore, menopause can be a risk factor for type-2 diabetes, mainly due to a deceased proliferation of $\beta$-cells.

Keywords

References

  1. Rahier J, Goebbels RM, Henquin JC. 1983. Cellular com-position of the human diabetic pancreas. Diabetologia 24: 366-371
  2. White MF. 1998. The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182: 3-11 https://doi.org/10.1023/A:1006806722619
  3. Kulkami RN, Jhala US, Wimiay JN, Krajewski S, Montminy M, Kahn CR. 2004. PDX-l haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 114: 828-836 https://doi.org/10.1172/JCI21845
  4. Withers DJ, Gutien-ez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bemal D, Pons S, Shulman GI, Bonner-Weir S, White MF. 1998. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391: 900-904 https://doi.org/10.1038/36116
  5. Hirose H, Lee YH, Inman LR, Nagasawa Y, Johnson JH, Unger RH. 1996. Defective fatty acid-mediated beta-cell compensation in Zucker diabetic fatty rats. Pathogenic implications for obesity-dependent diabetes. J Biol Chem 271: 5633-5637 https://doi.org/10.1074/jbc.271.10.5633
  6. Milbum JL Jr, Hirose H, Lee YH, Nagasawa Y, Ogawa A, Ohneda M, BeltrandelRio H, Newgard CB, Johnson JH, Unger RH. 1995. Pancreatic beta-cells in obesity. Ev-idence for induction of functional, morphologic, and met-abolic abnormalities by increased long chain fatty acids. J Biol Chem 270: 1295-1299 https://doi.org/10.1074/jbc.270.3.1295
  7. Lee CC, Kasa-Vubu JZ, Supiano MA. 2004. Androgenicity and obesity are independently associated with insulin sen-sitivity in postmenopausal women. Metabolism 53: 507-512 https://doi.org/10.1016/j.metabol.2003.10.018
  8. Shoelson SE, Lee J, Yuan M. 2003. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27: S49-52 https://doi.org/10.1038/sj.ijo.0802501
  9. Axen KV, Dikeakos A, Sclafani A. 2003. High dietary fat promotes syndrome X in nonobese rats. J Nutr 133: 2244-2449
  10. Friday KE, Dong C, Fontenot RU. 2001. Conjugated equine estrogen improves glycemic control and blood lipoproteins in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 86: 48-52 https://doi.org/10.1210/jc.86.1.48
  11. Andersson B, Mattsson L, Hahn L, Marin P, Lapidus L, Holm G, Bengtsson BA, Bjorntorp P. 1997. Estrogen replacement therapy decreases hyperandrogenicity and im-proves glucose homeostasis and plasma lipids in post-menopausal women with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82: 638-643 https://doi.org/10.1210/jc.82.2.638
  12. Hosokawa YA, Hosokawa H, Chen C, Leahy JL. 1996. Mechanism of impaired glucose-potentiated insulin-secretion in diabetic 90 percent pancreatectomy rats-Study using glucagon-like peptide-l (7-37). J Clin Invest 97: 180-186 https://doi.org/10.1172/JCI118387
  13. Picard F, Deshaies Y, Lalonde J, Samson P, Labrie C, Belanger A, Labrie F, Richard D. 2000. Effects of the estrogen antagonist EM-652. HCI on energy balance and lipid metabolism in ovahectomized rats. Int J Obes Relat Metab Disord 24: 830-840 https://doi.org/10.1038/sj.ijo.0801240
  14. Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y, Uchino H, Giacca A, McGarry JD. 2002. The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51: 1825-1833 https://doi.org/10.2337/diabetes.51.6.1825
  15. Choi SB, Park S. 2002. Does fluoxetine administration influence insulin resistance in 90% pancreatectomized rats? Metabolism 51: 38-43 https://doi.org/10.1053/meta.2002.26712
  16. Oddeti PR, Borgrglio A, Pascal AD, Rolandi R, Adezati L. 1990. Prevention of diabetes-increased aging effect on rat collagen linked fluorescence by ammoguanine and rutin. Diabetes 39: 796-802 https://doi.org/10.2337/diabetes.39.7.796
  17. Hennige AM, Burks DJ, Ozcan U, Kulkarm RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, Zakaria M, Mossa-Basha M, White MF. 2003. Upregulation of insulin receptor substrate-2 in pancreatic beta cells pre-vents diabetes. J Clin Invest 112: 1521-1532 https://doi.org/10.1172/JCI18581
  18. Committee of SAS Institute. 1985. Guide for personal com-puters. SAS Institutes Inc, Cary, NC. p 257-260
  19. Park S, Park CH, Jun DW, Choi SB. 2004. A high car-bohydrate diet induces insulin resistance through decreased glucose utilization in ovanectomized rats. Kr J InternalMed 19: 87-92
  20. Kimura M, Irahara M, Yasui T, Saito S, Tezuka M, Yamano S, Kamada M, Aono T. 2002. The obesity m bilateral ovanectomized rats is related to a decrease in the ex-pression of leptin receptors in the brain. Biochem Biophys Res Comm 290: 1349-1353 https://doi.org/10.1006/bbrc.2002.6355
  21. Burguera B, Hofbauer LC, Thomas T, Gori F, Evans GL, Khosla S, Riggs BL, Tumer RT. 2001. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology 142: 3546-3553 https://doi.org/10.1210/en.142.8.3546
  22. Friday KE, Dong C, Fontenot RU. 2001. Conjugated equine estrogen improves glycemic control and blood lipoproteins in postmenopausal women with type 2 diabetes. J Ctin Endocrin Metab 86: 48-52 https://doi.org/10.1210/jc.86.1.48
  23. Hirose H, Lee YH, Inman LR, Nagasawa Y, Johnson YH, Unger RH. 1996. Defective fatty acid-mediated $\beta$-cell compensation in Zucker diabetic fatty rats. pathogenic implications for obesity-dependent diabetes. J Biol Chem 271: 5633-5637 https://doi.org/10.1074/jbc.271.10.5633
  24. Pansini F, Bonaccorsi G, Genovesi F, Folegatti MR, Bagni B, Bergamini CM, Mollica G. 1990. Influence of estrogens on serum free fatty acid levels in women. J Clin Endo-crinol Metab 71: 1387-1389 https://doi.org/10.1210/jcem-71-5-1387
  25. Shimabukuro M, Zhou YT, Levi M, Unger RH. 1998. Fatty acid-induced $\beta$ cell apoptosis: A link between obesity and diabetes. Proc Natl Acad Sci USA 95: 2498-2502 https://doi.org/10.1073/pnas.95.5.2498