Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

Santos, Cristiane dos; Ferreira, Francielle Batista D.; Gonçalves-Neto, Luiz M.; Taboga, Sebastião Roberto; Boschero, Antônio Carlos; Rafacho, Alex

doi:10.1139/cjpp-2014-0259

Cited by 17 publications

(26 citation statements)

References 45 publications

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“…injection of dexamethasone as DEX group. The 4-VCD and dexamethasone dosing were based on previous publications [28][29][30][31]. Administration of 4-VCD during post-weaning window is known to render a state of early perimenopause and menopause when rats exceed around 60 and 120 days [8,15], which made this an useful experimental model for investigation of the effects of reduced ovarian function without aging as a confounding factor or the abrupt cessation of circulating ovarian hormones in ovariectomized rats [1].…”

Section: -Vcd and Dexamethasone Treatmentsmentioning

confidence: 99%

“…Administration of 4-VCD during post-weaning window is known to render a state of early perimenopause and menopause when rats exceed around 60 and 120 days [8,15], which made this an useful experimental model for investigation of the effects of reduced ovarian function without aging as a confounding factor or the abrupt cessation of circulating ovarian hormones in ovariectomized rats [1]. Dexamethasone at the dose and period administered is known to produce significant glucose metabolism side effects including glucose intolerance and reduction of insulin sensitivity, which make this a valuable tool for challenging glucose metabolism experimentally [23,24,[30][31][32].…”

Section: -Vcd and Dexamethasone Treatmentsmentioning

confidence: 99%

“…A 50% glucose solution pre-warmed at 36 C (2 g/kg, b.w., i.p.) was immediately administered, and blood samples were collected from the tail tip at 20, 40, 80 and 120 min for blood glucose measurements [23,30,31]. At minute 20, additional blood volume (60 mL) was collected in EDTA-NaF-containing tubes for plasma separation and posterior quantification of insulin as a measure of the in vivo glucosestimulated insulin secretion [23,24].…”

Section: Intraperitoneal Glucose Tolerance Test (Ipgtt) and In Vivo Gmentioning

confidence: 99%

“…To study morphological and morphometrical aspects of ovary and endocrine pancreas, 6 pars of ovaries and 6 pancreases (splenic fragment) from each group in a random selection were excised and processed according to a previous description [24,31] with the exception that the fixative solution used for ovaries' fixation was 4% paraformaldehyde and for pancreases' fixation was 10% neutral buffered formalin. The organs were withdrawn from rats subjected to the oral glucose challenging.…”

Section: Ovarian and Pancreas Tissue Morphology And Morphometrymentioning

confidence: 99%

“…Histology and immunostaining: Ovary morphology was observed in hematoxylin & eosin stained sections. Pancreas sections were immunostained with insulin by the immunoperoxidase method and counterstained with hematoxylin according previous publication [24,31]. Follicular ovarian morphometry: For identification of 4-VCD effects on follicular development, three interspaced (250 mm) sections per ovary were cut and had preantral follicles and Corpus luteum counted, according to the classification described by Luo and collaborators [35].…”

Section: Ovarian and Pancreas Tissue Morphology And Morphometrymentioning

confidence: 99%

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Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment

Battiston

Santos

Barbosa

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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4-vinilcyclohexene diepoxide (4-VCD) causes premature ovarian failure and may result in estrogen deficiency, characterizing the transition to estropause in rodents (equivalent to menopause in women). Estropause/menopause is associated with metabolic derangements such as glucose intolerance and insulin resistance. Glucocorticoids (GCs) are known to exert diabetogenic effects. Thus, we aimed to investigate whether rats with premature ovarian failure are more prone to the diabetogenic effects of GC. For this, immature female rats received daily injections of 4-VCD [160mg/kg body weight (b.w.), intraperitoneally (i.p.)] for 15 consecutive days, whereas control rats received vehicle. After 168days of the completion of 4-VCD administration, rats were divided into 4 groups: CTL-received daily injections of saline (1mL/kg, b.w., i.p.) for 5days; DEX-received daily injections of dexamethasone (1mg/kg, b.w., i.p.) for 5days; VCD-treated as CTL group; VCD+DEX-treated as DEX group. Experiments and euthanasia occurred one day after the last dexamethasone injection. 4-VCD-treated rats exhibited ovary hypotrophy and reduced number of preantral follicles (p<0.05). Premature ovarian failure had no impact on the body weight gain or food intake, but both were reduced by the effects of dexamethasone. The increase in blood glucose, plasma insulin and triacylglycerol levels as well as the reduction in insulin sensitivity caused by dexamethasone treatment was not exacerbated in the VCD+DEX group of rats. Premature ovarian failure did change neither the hepatic content of glycogen and triacylglycerol nor the glycerol release from perigonadal adipose tissue. Glucose intolerance was observed in the VCD group after an ipGTT (p<0.05), but not after an oral glucose challenge. Glucose intolerance and compensatory pancreatic β-cell mass caused by GC were not modified by ovarian failure in the VCD+DEX group. We conclude that reduced ovarian function has no major implications on the diabetogenic effects promoted by GC treatment, indicating that other factors related to aging may make rats more vulnerable to GC side effects on glucose metabolism.

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