Signal transduction of the insulin secretion induced by the chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, and its role in glucose and lipid metabolism.

A chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (DMU 101), was synthesized using classic base catalysis and Claisen-Schmidt condensation, and then screened for its antidiabetic properties. The compound's effects on glucose and lipid metabolism were assayed in rats that were treated acutely and for a short time to elucidate its mechanism of action, evaluating glucose tolerance and lactate dehydrogenase activity in response to chalcone analogue administration. The chalcone's in vitro and ex vivo effects on glycogen, glucose, lipid and lipolysis were also investigated, as well as the mechanism by which it induces 45Ca2+ influx-mediated insulin secretion. The analogue (10 mg/kg) diminished glycemia, without inducing acute cell damage, increased glycogen content in the skeletal muscle and reduced serum triacylglycerol and total cholesterol, but did not alter high-density lipoprotein or low-density lipoprotein. Chalcone (10 µM) stimulated glucose uptake in the soleus muscle and did not modulate in vitro or ex vivo lipolysis. This analogue also increased insulin secretion by triggering calcium influx and blocking ATP-sensitive K+ channels and voltage-dependent calcium channels. However, it also modulated stored calcium via sarco/endoplasmic reticulum calcium ATPase (SERCA) and ryanodine receptor (RYR) activity. These findings indicate that this chalcone may induce cellular repolarization via a mechanism mediated by calcium-dependent potassium channels.

1α,25-(OH)2 vitamin D3 prevents insulin resistance and regulates coordinated exocytosis and insulin secretion.

Vitamin D3 is associated with improvements in insulin resistance and glycemia. In this study, we investigated the short-term effect of 1α,25(OH)2 Vitamin D3 (1,25-D3) and cholecalciferol (vitamin D3) on the glycemia and insulin sensitivity of control and dexamethasone-induced insulin-resistance rats. 45Ca2+ influx responses to 1,25-D3 and its role in insulin secretion were investigated in isolated pancreatic islets from control rats. In vivo, 5 d treatment with 1,25-D3 (i.p.) prevented insulin resistance in dexamethasone-treated rats. Treatment with 1,25-D3 improved the activities of hepatic enzymes, serum lipids and calcium concentrations in insulin-resistant rats. 25-D3 (o.g.) does not affect insulin resistance. In pancreatic islets, 1,25-D3 increased insulin secretion and stimulated rapid response 45Ca2+ influx. The stimulatory effect of 1,25-D3 on 45Ca2+ influx was decreased by diazoxide, apamine, thapsigargin, dantrolene, 2-APB, nifedipine, TEA, PKA, PKC, and cytoskeleton inhibitor, while it was increased by glibenclamide and N-ethylmaleimide. The stimulatory effect of 1,25-D3 on 45Ca2+ influx involves the activation of L-type VDCC, K+-ATP, K+-Ca2+, and Kv channels, which augment cytosolic calcium. These ionic changes mobilize calcium from stores and downstream activation of PKC, PKA tethering vesicle traffic and fusion at the plasma membrane for insulin secretion. This is the first study highlighting the unprecedented role of 1,25-D3 (short-term effect) in the regulation of glucose homeostasis and on prevention of insulin resistance. Furthermore, this study shows the intracellular ß-cell signal transduction of 1,25-D3 through the modulation of pivotal ionic channels and proteins exhibiting a coordinated exocytosis of vesicles for insulin secretion.

Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle.

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.

Cuidados à pessoa suspeita de COVID-19 com sinais de gravidade na Atenção Primária à Saúde / Care of suspected person of covid-19 with severe signs in primary health care

Objetivo: Descrever o processo de elaboração e a implementação de um checklist de cuidados à pessoa suspeita do novo coronavírus com sinais de gravidade na Atenção Primária à Saúde. Métodos: Relato de experiência de um Centro de Saúde da região da Grande Florianópolis, Santa Catarina, desenvolvida em duas etapas: elaboração e implementação de um checklist de cuidados para pessoas com sintomas respiratórios graves. Resultados: O checklist, elaborado coletivamente por enfermeiros e médicos em quatro versões, constituiu-se, na sua versão final dos itens: sinais vitais, ventilação, procedimentos, medicação, biossegurança, cuidados com a família, alergia medicamentosa, comunicação com outros pontos da Rede de Atenção à Urgência e observações. Implementado no atendimento a uma pessoa com sintomas respiratórios graves suspeita do novo coronavírus, o checklist proporcionou maior segurança no cuidado, acesso rápido às informações e com garantia de que nenhum dado fosse negligenciado, ademais favoreceu o diálogo entre os profissionais durante o atendimento, a comunicação com a família e com outros pontos da Rede de Atenção às Urgências. Conclusões: O checklist elaborado, claro e objetivo na sua implementação, supriu a necessidade de se garantir, na Atenção Primária à Saúde, uma assistência à pessoa suspeita do novo coronavírus com sinais de gravidade com mais qualidade e segurança. (AU)

Objective: To describe the elaboration process and implementation of a care checklist to suspected persons of the new coronavirus with severe signs in Primary Health Care. Methods: Report of experience of a health center in the region of the greater Florianópolis, Santa Catarina, developed in two phases: elaboration and implementation of a checklist for care of people with severe respiratory symptoms. Results: The checklist was elaborated collectively by nurses and physicians in four versions, and its final version consists of the items: vital signs, ventilation, procedures, medication, biosafety, family care, drug allergy, communication with other branches within the Urgent Care Network, and observations. Implemented in the care of persons with severe respiratory symptoms suspected of the new coronavirus, the checklist provided greater safety in care, quick access to information and it guaranteed that no data was neglected, in addition it facilitated the dialogue between professionals during the service, the communication with the family and with other branches within the Urgent Care Network. Conclusions: The elaborated checklist was clear and objective in its implementation, and fulfilled the need to guarantee more quality and safety in assistance of suspected person of the new coronavirus with severe signs in Primary Health Care. (AU)

Objetivo: Describir el proceso de elaboración y la implementación de un checklist de cuidados a la persona sospechosa del nuevo coronavirus con signos de gravedad en la Atención Primaria de Salud. Método: Relato de experiencia de un Centro de Salud de la región de la Grande Florianópolis, Santa Catarina, desarrollada en dos etapas: elaboración e implementación de un checklist de cuidados para personas con síntomas respiratorios severos. Resultados: El checklist elaborado colectivamente por enfermeras y médicos en cuatro versiones, consistió en su versión final de los ítems: signos vitales, ventilación, procedimientos, medicamentos, bioseguridad, cuidados con la familia, alergia a medicamentos, comunicación con otros puntos de la Red de Atención de Urgencia y observaciones. Implementado en la atención de una persona con síntomas respiratorios severos y sospechosa del nuevo coronavirus, el checklist proporcionó una mayor seguridad en el cuidado, acceso rápido a la información y garantía que ningún dato fuera desestimado. Además favorecer el diálogo entre profesionales durante la atención, la comunicación con la familia y con otros puntos de la Red de Atención de Urgencias. Conclusiones: El checklist elaborado, claro y objetivo en su implementación, cumplió la necesidad de garantizar en la Atención Primaria de Salud, la asistencia a la persona sospechosa del nuevo coronavirus con signos de gravedad con más calidad y seguridad. (AU)

Sulfonyl(thio)urea derivative induction of insulin secretion is mediated by potassium, calcium, and sodium channel signal transduction.

AIM: To investigate the mechanism of action of sulfonyl(thio)urea derivative (SD) on glycemia and on insulin secretion in pancreatic islets. METHODS: Wistar rats were divided into hyperglycemic control group, rats received 4 g/kg body weight glucose plus sitagliptin 10 mg/kg (p.o.); hyperglycemic plus SD 10 mg/kg (p.o.); hyperglycemic plus SD plus sitagliptin. Blood was collected before glucose overloading (zero time), and at 15, 30, 60, and 180 min after glucose, from the afore mentioned groups for glycemia and glucagon-like peptide 1 (GLP-1) measurements and intestinal disaccharidases activity. Pancreatic islets were isolated for the calcium influx and insulin secretion in in vitro studies. RESULTS: SD reduced glycemia and increased GLP-1 secretion, while inhibited sucrase and lactase activity. This SD (1.0 and 10.0 µM) stimulated calcium influx in a similar percentile to that of glibenclamide, and in a nonsynergic manner. In addition, the trigger effect of SD on calcium influx was through the K+ -ATP-dependent channels, and partially by activating voltage-dependent K + channels and voltage-dependent calcium channels. Furthermore, SD-stimulated Na + and Ca 2+ entry, induced by the transient receptor potential ankyrin 1 and by modulation of Na + /Ca 2+ exchange. The activation of these pathways by SD culminated in in vitro insulin secretion, reinforcing the critical role of K + -ATP channels in the secretagogue effect of SD. CONCLUSIONS: SD diminish glycemia by inducing GLP-1 secretion and inhibiting disaccharidases. To our knowledge, this is the first report of an insulin secretagogue effect of SD that is mediated by potassium and calcium, as well as sodium, signal transduction.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin.