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Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Am J Physiol Heart Circ Physiol 289(4):H1335-H1342

Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.
AJP Heart and Circulatory Physiology (Impact Factor: 4.01). 11/2005; 289(4):H1335-42. DOI: 10.1152/ajpheart.00399.2005
Source: PubMed

ABSTRACT Differences in gender are in part responsible for the development of insulin resistance (IR) and associated hypertension. Currently, it is unclear whether these differences are dictated by gender itself or by the relative changes in plasma estrogen and/or testosterone. We investigated the interrelationships between testosterone and estrogen in the progression of IR and hypertension in vivo in intact and gonadectomized fructose-fed male rats. Treatment with estrogen significantly reduced the testosterone levels in both normal chow-fed and fructose-fed rats. Interestingly, fructose feeding induced a relative increase in estradiol levels, which did not affect IR in both intact and gonadectomized fructose-fed rats. However, increasing the estrogen levels improved insulin sensitivity in both intact and gonadectomized fructose-fed rats. In intact males, fructose feeding increased the blood pressure (140 +/- 2 mmHg), which was prevented by estrogen treatment. However, the blood pressure in the fructose-fed estrogen rats (125 +/- 1 mmHg) was significantly higher than that of normal chow-fed (113 +/- 1 mmHg) and fructose-fed gonadectomized rats. Estrogen treatment did not affect the blood pressure in gonadectomized fructose-fed rats (105 +/- 2 mmHg). These data suggest the existence of a threshold value for estrogen below which insulin sensitivity is unaffected. The development of hypertension in this model is dictated solely by the presence or absence of testosterone. In summary, the development of IR and hypertension is governed not by gender per se but by the interactions of specific sex hormones such as estrogen and testosterone.

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    • "10 weeks allopurinol 6 weeks [62] Thromboxane synthase inhibitors: 60% fructose in diet 7 weeks dazmegrel 7 weeks ↓ blood pressure [86] Lipid-lowering agents: 66% fructose in diet 6 weeks rosuvastatin 5 weeks ↓ plasma insulin [87] Sex hormones: 66% fructose in diet 10 weeks gonadectomy 6 weeks ↓ blood pressure [88] 60% fructose in diet 9 weeks 9 weeks [89] 6-7 weeks estrogen 6-7 weeks [90] Gene therapy: 10% fructose in drinking water 5 weeks human tissue kallikrein cDNA 3 weeks ↓ plasma insulin, ↓ blood pressure [91] "
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    • "10 weeks allopurinol 6 weeks [62] Thromboxane synthase inhibitors: 60% fructose in diet 7 weeks dazmegrel 7 weeks ↓ blood pressure [86] Lipid-lowering agents: 66% fructose in diet 6 weeks rosuvastatin 5 weeks ↓ plasma insulin [87] Sex hormones: 66% fructose in diet 10 weeks gonadectomy 6 weeks ↓ blood pressure [88] 60% fructose in diet 9 weeks 9 weeks [89] 6-7 weeks estrogen 6-7 weeks [90] Gene therapy: 10% fructose in drinking water 5 weeks human tissue kallikrein cDNA 3 weeks ↓ plasma insulin, ↓ blood pressure [91] "
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    • "Female B6 mice have better glucose tolerance and insulin sensitivity than males because of better sensitivity of liver and fat tissues to insulin in the females (Goren et al., 2004). This differential regulation of insulin resistance by gender is likely because of gonadal production of estrogen in females (Vasudevan et al., 2005; Yakar et al., 2006). We used HOMA-IR calculated from fasting plasma glucose and insulin to estimate insulin resistance. "
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