Potential Binding Sites for Taurine on the Insulin Receptor: A Molecular Docking Study.

Taurine has been reported to improve the action of insulin in normal, pre-, and diabetic conditions. However, the mechanism by which this amino acid ameliorates insulin sensitivity is not yet completely understood. Insulin acts on target tissues by interacting with the extracellular portion of a tyrosine kinase receptor, whose structure is known as the ectodomain (ECD) of the insulin receptor (IR). Some studies indicate that taurine can bind to the IR, which would contribute to its beneficial actions on glucose homeostasis. However, the binding mode of the amino acid on the IR ECD is unknown. Herein, using in silico experiments, we aimed to verify whether taurine may be an agonist of the IR and also to demonstrate the potential binding sites of taurine on the IR ECD. Molecular modeling predicted that taurine might interact with the three largest pocket sites for ligands present in the IR ECD. Taurine demonstrated high-energy interactions with these pockets, showing the highest affinity and highest molecular interaction with pocket 1, followed by decreasing energies and binding to pockets 2 and 3 of the IR ECD. The taurine interaction sites on the IR were not the same as the insulin interaction sites. Thus, these data indicate that taurine may be an agonist of the IR ECD, acting with high affinity at pocket 1 of the ECD. The predicted binding sites observed in this study probably constitute the regions of interaction of taurine on the IR and contribute to the mechanism by which taurine ameliorates insulin signaling pathway activation, thereby improving glucose homeostasis and the other cellular functions that are regulated by this intracellular signaling cascade.

Dietary Protein Modulates the Efficacy of Taurine Supplementation on Adaptive Islet Function and Morphology in Obesity.

Adaptation of islet ß-cell mass and function under limiting or excess nutrient availability is critical for maintenance of glucose homeostasis. Taurine regulates islet function of obese mice in normal and low dietary protein conditions, but whether this involves remodeling of the endocrine pancreas architecture is not well understood. Here, we carried functional and morphometric evaluation of the endocrine pancreas of normal and protein-restricted mice fed a high-fat diet (HFD) and investigated the role of taurine supplementation. Weaned mice were placed in a normal (C) or a low-protein diet (R) for 6 weeks, followed by HFD for 8 weeks (CH and RH). Half of HFD groups received 5% taurine supplementation since weaning (CHT and RHT) until the end of the experiment. Isolated islets from both CH and RH groups showed increased insulin release in association with increased pancreas weight and independently of changes in islet or ß-cell area. In normal protein CHT mice, taurine supplementation prevented obesity-induced insulin hypersecretion and promoted increased islet and ß-cell areas in association with increased protein expression of the proliferation marker, PCNA. On a low-protein background, taurine effects on islet function and morphology were blunted, but it prevented obesity-induced DNA fragmentation. In summary, taurine regulates islet function and morphology to improve the adaptive response to diet-induced obesity, but these effects are dependent on adequate dietary protein levels.

Combined oral contraceptive in female mice causes hyperinsulinemia due to ß-cell hypersecretion and reduction in insulin clearance.

Oral contraception is the most commonly used interventional method in the world. However, several women employ the continuous use of these hormones to avoid pre- and menstruation discomforts. Some studies indicate that oral contraceptives are associated with disturbances in glycemia and the effects of the use of a continuous regime are poorly elucidated. Herein, we evaluated the effects of the continuous administration of a combined oral contraceptive (COC) composed by ethinyl estradiol (EE) and drospirenone (DRSP) on glucose homeostasis in female mice. Adult Swiss mice received 0.6 µg EE and 60 µg DRSP (COC group) or vehicle [control (CTL)] daily by gavage for 35 days. COC treatment had no effect on body weight or adiposity, but increased uterus weight and induced hepatomegaly. Importantly, COC females displayed normal glycemia and glucose tolerance, but hyperinsulinemia and lower plasma C-peptide/insulin ratio, indicating reduced insulin clearance. Furthermore, COC mice displayed reduced protein content of the ß subunit of the insulin receptor (IRß) in the liver. Additionally, pancreatic islets isolated from COC mice secreted more insulin in response to increasing glucose concentrations. This effect was associated with the activity of steroid hormones, since INS-1E cells incubated with EE plus DRSP also secreted more insulin. Therefore, we provide the first evidence that the continuous administration of EE and DRSP lead to hyperinsulinemia, due to enhancement of insulin secretion and the reduction of insulin degradation, which possibly lead to the down-regulation of hepatic IRß. These findings suggest that the continuous administration of COC could cause insulin resistance with the prolongation of treatment.

[Evaluating the existence of oral infection control in patients admitted in state hospitals in Rio de Janeiro]. / Avaliação da existência de controle de infecção oral nos pacientes internados em hospitais do estado do Rio de Janeiro.

The aim of the present study is to ascertain whether an oral infection control protocol is being used in Rio de Janeiro State hospitals. Sixty two hospitals, both public and private have been surveyed. When asked whether any procedure was being adopted with admitted patients (in case of ICU patients), 39% of the hospitals responded positively. Among all institutions surveyed, only 15% conduct a regular plaque control protocol in admitted patients. Studies have shown that there is an inter-relationship between periodontal disease and systemic diseases, such as cardiovascular disease, osteoporosis, preterm births and low birthweight, diabetes and respiratory diseases. The oral cavity is considered a potent reservoir of respiratory pathogens. Based on these findings, it has become evident that oral hygiene is an important means of preventing a number of diseases. Thus the need arises not only to create an oral cavity infection control protocol that will contribute to reduce mortality in admitted patients but also to propose preventive measures towards this end.