Abstract
BackgroundThere is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.MethodsFemale Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured.ResultsCompared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups.ConclusionsAndronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.
Highlights
There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS)
Body weight and blood glucose curves Andronate-treated two groups exhibited a significant increase in the mean body weight at the end of the study (Figure 4A)
We here demonstrate that andronate with high-fat diet (HFD) rats replicate both the ovarian and the metabolic syndrome features of human PCOS, including PCO morphology, irregular cycles, increased body weight, hyperlipidemia, and insulin resistance
Summary
There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age [1] and is the most frequent cause of hyperandrogenism and anovulation [2]. PCOS is strongly associated with abdominal obesity, hyperinsulinemia, insulin resistance, and type 2 diabetes [3]. Once a diagnosis of PCOS is confirmed, it is imperative to assess the woman for diabetes mellitus (DM) risk factors. Insulin resistance (IR) is increased in age-matched PCOS women and is linked to hyperandrogenism [8]. No consensus recommendation for the assessment of DM risk factors exists, measurement of glucose metabolism, lipid screening, and measurements of insulin concentrations have been suggested [9]
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