Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment.
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.
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil.
Francielle Garghetti
FG
Battiston
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil.
Cristiane
C
Dos Santos
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil.
Amanda Marreiro
AM
Barbosa
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil.
Sibele
S
Sehnem
Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ. Estadual Paulista-IBILCE/UNESP, São José do Rio Preto, SP, Brazil.
Ellen Cristina Rivas
ECR
Leonel
Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ. Estadual Paulista-IBILCE/UNESP, São José do Rio Preto, SP, Brazil.
Sebastião Roberto
SR
Taboga
Department of Morphology, Center of Biological Sciences, School of Dentistry of Ribeirão Preto, São Paulo University-USP, Ribeirão Preto, SP, Brazil.
Janete A
JA
Anselmo-Franci
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil.
Fernanda Barbosa
FB
Lima
Department of Physiological Sciences and Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Florianópolis, Brazil. Electronic address: alex.rafacho@ufsc.br.
Alex
A
Rafacho
D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016922:Cellular Senescence; D053138:Cyclohexenes / Q000009:adverse effects*; D003907:Dexamethasone / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000737:chemistry; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology; D008099:Liver / Q000378:metabolism; D006080:Ovarian Follicle / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000009:adverse effects; D014753:Vinyl Compounds / Q000009:adverse effects*
D001786:Blood Glucose; D053138:Cyclohexenes; D005938:Glucocorticoids; D007328:Insulin; D013256:Steroids; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide; D003907:Dexamethasone; D006003:Glycogen; D005947:Glucose
Aging; Female; Metabolism; Ovarian failure; Senescence; Steroid hormones