The function of pancreatic β-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ERα and ERβ, are important molecules involved in glucose metabolism, yet their role in pancreatic β-cell physiology is still greatly unknown. In this report we show that both ERα and ERβ are present in pancreatic β-cells. Long term exposure to physiological concentrations of 17β-estradiol (E2) increased β-cell insulin content, insulin gene expression and insulin release, yet pancreatic β-cell mass was unaltered. The up-regulation of pancreatic β-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ERα and ERβ agonists as well as ERαKO and ERβKO mice suggests that the estrogen receptor involved is ERα. The up-regulation of pancreatic insulin content by ERα activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.

Melatonin is an indolamine mostly produced in the pineal gland, soluble in water, and highly lipophilic, which allows it to readily cross the blood-brain barrier. Melatonin possesses antioxidant properties and its long-term administration in rodents has not been found to cause noteworthy side effects. In the present work, we found that millimolar concentrations of this indolamine reduced cell growth of C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression from G₁ to S phase of the cell cycle. Intraperitoneal administration of 15 mg/kg body weight of melatonin to rats previously injected in the flank with C6 glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of cell growth does not depend on melatonin membrane receptor activation whereas it seemingly relates to the reduction of intracellular basal free radical levels by 30%. Increase of basal redox state of the cells and constitutive activation of tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the extracellular signal–regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase C (PKC) signaling pathways, contribute to the progression of the gliomas leading to the constitutive activation of the redox-dependent survival transcription factor nuclear factor κB (NF-κB). The antioxidant effect of melatonin in C6 cells is associated to inhibition of NF-κB and Akt, but not of ERK1/2. The antiproliferative effect of the indolamine on these cells is partially abolished when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate, thus indicating that the ability of melatonin to change cellular redox state may be inactivating the pathway RTK/PKC/Akt/NF-κB. (Cancer Res 2006; 66(2): 1081-8)

Preventing the onset of dementia and Alzheimer’s disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these diseases and different sociodemographic and clinical features. In this regard, a case-control study was conducted in Spain in 2018–2019. The definition of a case was: A person ≥ 65 years old with dementia and/or AD and a score of 5–7 on the Global Deterioration Scale (GDS). The sample consisted of 125 controls; among the cases, 96 had dementia and 74 had AD. The predictor variables were depression, dyslipidemia, type 2 diabetes mellitus, and hypertension. The results showed that depression, diabetes mellitus, and older age were associated with an increased likelihood of developing AD, with an Odds Ratio (OR) of 12.9 (95% confidence interval (CI): 4.3–39.9), 2.8 (95% CI: 1.1–7.1) and 1.15 (95% CI: 1.1–1.2), respectively. Those subjects with treated dyslipidemia were less likely to develop AD (OR 0.47, 95% CI: 0.22–1.1). Therefore, depression and diabetes mellitus increase the risk of dementia, whereas treated dyslipidemia has been shown to reduce this risk.