PPAR-gamma agonists directly stimulate progesterone and IGFBP-1 production, inhibit estradiol and testosterone production, abolish insulin-induced stimulation of testosterone production and insulin-dependent stimulation of estradiol production in the presence of FSH, and enhance insulin-induced inhibition of IGFBP-1 production in human ovarian cells. PPAR-gamma represents a novel system of ovarian regulation.

IntroductionType 2 diabetes mellitus (T2DM) is caused by insulin resistance and pancreatic islet insufficiency. Vitamin D deficiency and T2DM share common demographic characteristics for their risk groups (elderly, darkskinned individuals, obese), and patients with T2DM are reported to have higher rates of vitamin D deficiency.1 Epidemiological studies also suggest a higher prevalence of metabolic syndrome and its components (central obesity, hypertension, dyslipidemia, and glucose intolerance) among individuals with low circulating vitamin D concentrations. AbstractBackground: Epidemiological studies suggest a higher prevalence of metabolic syndrome and its components among individuals with vitamin D deficiency. The aim of the present study was to determine whether vitamin D treatment improves glucose control and insulin sensitivity in Type 2 diabetes mellitus (T2DM). Methods: Subjects with T2DM and serum 25-hydroxyvitamin D (25(OH)D) concentrations <25 ng ⁄ mL were randomized to receive 400 IU (Group 1) or 1200 IU (Group 2) cholecalciferol for 4 months. Fasting plasma glucose, glycosylated hemoglobin (HbA1c), Quantitative Insulin Sensitivity Check Index (QUICKI), serum lipid levels and serum adiponectin were measured at baseline and at 4 months. Results: Mean 25(OH)D levels increased in both groups (from 17.6 ± 1.5 to 25.5 ± 1.8 ng ⁄ mL in Group 1 and from 15.6 ± 1.4 to 27.4 ± 2.4 ng ⁄ mL in Group 2; P £ 0.001 vs baseline for each group). No significant differences were noted in fasting plasma glucose, HbA1c, QUICKI, serum adiponectin, and lipid levels compared with baseline within groups or between the two groups. Conclusions: In the present pilot study, conventional vitamin D treatment at a level improving, but not optimizing, serum 25(OH)D did not improve glycemia, insulin sensitivity, or lipid profile. However, diabetes and lipids were relatively well controlled at baseline. Future studies should be designed to achieve optimal concentrations of serum 25(OH)D (at least >32 ng ⁄ mL) and should include subjects showing more abnormal parameters of glycemia, lipid, and insulin sensitivity at baseline.

Insulin and TZDs independently stimulate expression of PPAR-gamma, insulin receptor, IRS-1, and StAR protein in human ovarian cells. Thus, PPAR-gamma, insulin receptor with its signaling pathways, and StAR protein constitute a novel human ovarian regulatory system with complex interactions among its components.

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