Protein malnutrition early in life increased apoptosis but did not alter the ß-cell mass during gestation.

We evaluated whether early-life protein restriction alters structural parameters that affect ß-cell mass on the 15th day and 20th day of gestation in control pregnant (CP), control non-pregnant (CNP), low-protein pregnant (LPP) and low-protein non-pregnant (LPNP) rats from the fetal to the adult life stage as well as in protein-restricted rats that recovered after weaning (recovered pregnant (RP) and recovered non-pregnant). On the 15th day of gestation, the CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. The ß-cell mass was lower in the low-protein group than that in the recovered and control groups. Gestation increased the ß-cell mass, ß-cell proliferation frequency and neogenesis frequency independently of the nutritional status. The apoptosis frequency was increased in the recovered groups compared with that in the other groups. On the 20th day of gestation, a higher proportion of islets smaller than the median was observed in the non-pregnant groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. ß-Cell mass was lower in the low-protein group than that in the recovered and control groups, regardless of the physiological status. The ß-cell proliferation frequency was lower, whereas the apoptosis rate was higher in recovered rats compared with those in the low-protein and control rats. Thus, protein malnutrition early in life did not alter the mass of ß-cells, especially in the first two-thirds of gestation, despite the increase in apoptosis.

Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice.

BACKGROUND: Interesterified fats have largely replaced the partially hydrogenated oils which are the main dietary source of trans fat in industrialized food. This process promotes a random rearrangement of the native fatty acids and the results are different triacylglycerol (TAG) molecules without generating trans isomers. The role of interesterified fats in metabolism remains unclear. We evaluated metabolic parameters, glucose homeostasis and inflammatory markers in mice fed with normocaloric and normolipidic diets or hypercaloric and high-fat diet enriched with interesterified palm oil. METHODS: Male Swiss mice were randomly divided into four experimental groups and submitted to either normolipidic palm oil diet (PO), normolipidic interesterified palm oil diet (IPO), palm oil high-fat diet (POHF) or interesterified palm oil high-fat diet (IPOHF) during an 8 weeks period. RESULTS: When compared to the PO group, IPO group presented higher body mass, hyperglycemia, impaired glucose tolerance, evidence of insulin resistance and greater production of glucose in basal state during pyruvate in situ assay. We also observed higher protein content of hepatic PEPCK and increased cytokine mRNA expression in the IPO group when compared to PO. Interestingly, IPO group showed similar parameters to POHF and IPOHF groups. CONCLUSION: The results indicate that substitution of palm oil for interesterified palm oil even on normocaloric and normolipidic diet could negatively modulate metabolic parameters and glucose homeostasis as well as cytokine gene expression in the liver and white adipose tissue. This data support concerns about the effects of interesterified fats on health and could promote further discussions about the safety of the utilization of this unnatural fat by food industry.

Protein restriction during pregnancy impairs intra-islet GLP-1 and the expansion of ß-cell mass.

We evaluated whether protein restriction during pregnancy alters the morphometry of pancreatic islets, the intra-islet glucagon-like peptide-1 (GLP-1) production, and the anti-apoptotic signalling pathway modulated by GLP-1. Control non-pregnant (CNP) and control pregnant (CP) rats were fed a 17% protein diet, and low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) groups were fed a 6% protein diet. The masses of islets and ß-cells were similar in the LPNP group and the CNP group but were higher in the CP group than in the CNP group and were equal in the LPP group and the LPNP group. Both variables were lower in the LPP group than in the CP group. Prohormone convertase 2 and GLP-1 fluorescence in α-cells was lower in the low-protein groups than in the control groups. The least PC2/glucagon colocalization was observed in the LPP group, and the most was observed in the CP group. There was less prohormone convertase 1/3/glucagon colocalization in the LPP group than in the CP group. GLP-1/glucagon colocalization was similar in the LPP, CP and CNP groups, which showed less GLP-1/glucagon colocalization than the LPNP group. The mRNA Pka, Creb and Pdx-1 contents were higher in islets from pregnant rats than in islets from non-pregnant rats. Protein restriction during pregnancy impaired the mass of ß-cells and the intra-islet GLP-1 production but did not interfere with the transcription of genes of the anti-apoptotic signalling pathway modulated by GLP-1.

Early protein restriction increases intra-islet GLP-1 production and pancreatic ß-cell proliferation mediated by the ß-catenin pathway.

PURPOSE: In the present study, we investigated whether intra-islet GLP-1 production and its modulation have a role in apoptosis, proliferation or neogenesis that is compromised by protein restriction during the foetal and suckling periods. METHODS: Exendin-4, a GLP-1 receptor agonist (treated groups), or saline (non-treated groups) was intraperitoneally administered for 15 days from 75 to 90 days of age in female adult rats consisting of offspring born to and suckled by mothers fed a control diet (control groups) and who had the same diet until 90 days of age or offspring born to and suckled by mothers fed a low-protein diet and who were fed the control diet after weaning until 90 days of age (protein-restricted group). RESULTS: The ß-cell mass was lower in the protein-restricted groups than in the control groups. Exendin-4 increased ß-cell mass, regardless of the mother's protein intake. The colocalization of GLP-1/glucagon was higher in the protein-restricted rats than in control rats in both the exendin-4-treated and non-treated groups. The frequency of cleaved caspase-3-labelled cells was higher in the non-treated protein-restricted group than in the non-treated control group and was similar in the treated protein-restricted and treated control groups. Regardless of treatment with exendin-4, Ki67-labelled cell frequency and ß-catenin/DAPI colocalization were elevated in the protein-restricted groups. Exendin-4 increased the area of endocrine cell clusters and ß-catenin/DAPI and FoxO1/DAPI colocalization regardless of the mother's protein intake. CONCLUSIONS: Protein restriction in early life increased intra-islet GLP-1 production and ß-cell proliferation, possibly mediated by the ß-catenin pathway.

Early weaning induces short- and long-term effects on pancreatic islets in Wistar rats of both sexes.

KEY POINTS: The World Health Organization recommends exclusive breastfeeding until 6 months of age as an important strategy to reduce child morbidity and mortality. Studies have associated early weaning with the development of obesity and type 2 diabetes in adulthood. In our model, we demonstrated that early weaning leads to increased insulin secretion in adolescent males and reduced insulin secretion in adult offspring. Early weaned males exhibit insulin resistance in skeletal muscle. Early weaning did not change insulin signalling in the muscle of female offspring. Taking into account that insulin resistance is one of the primary factors for the development of type 2 diabetes mellitus, this work demonstrates the importance of breastfeeding in the fight against this disease. ABSTRACT: Early weaning (EW) leads to short- and long-term obesity and diabetes. This phenotype is also observed in experimental models, in which early-weaned males exhibit abnormal insulinaemia in adulthood. However, studies regarding the effect of EW on pancreatic islets are rare. We investigated the mechanisms by which glycaemic homeostasis is altered in EW models through evaluations of insulin secretion and its signalling pathway in offspring. Lactating Wistar rats and their pups were divided into the following groups: non-pharmacological EW (NPEW): mothers were wrapped with an adhesive bandage on the last 3 days of lactation; pharmacological EW (PEW): mothers received bromocriptine to inhibit prolactin (1 mg/kg body mass/day) on the last 3 days of lactation; and control (C): pups underwent standard weaning at PN21. Offspring of both sexes were euthanized at PN45 and PN180. At PN45, EW males showed higher insulin secretion (vs. C). At PN170, PEW males exhibited hyperglycaemia in an oral glucose tolerance test (vs. C and NPEW). At PN180, EW male offspring were heavier; however, both sexes showed higher visceral fat. Insulin secretion was lower in EW offspring of both sexes. Males from both EW groups had lower glucokinase in islets, but unexpectedly, PEW males showed higher GLUT2, than did C. EW males exhibited lower insulin signalling in muscle. EW females exhibited no changes in these parameters compared with C. We demonstrated distinct alterations in the insulin secretion of EW rats at different ages. Despite the sex dimorphism in insulin secretion in adolescence, both sexes showed impaired insulin secretion in adulthood due to EW.

Protein restriction in early life increases intracellular calcium and insulin secretion, but does not alter expression of SNARE proteins during pregnancy.

NEW FINDINGS: What is the central question of this study? Does protein restriction in early life modify glucose-induced insulin secretion by altering [Ca2+ ]i and the expression of SNARE proteins in pancreatic islets from pregnant rats? What is the main finding and its importance? Protein restriction in early life increased the first phase of glucose-induced insulin secretion and [Ca2+ ]i without altering the expression of SNARE proteins during pregnancy. This finding contributes to our understanding of the mechanisms of altered insulin secretion and might provide new perspectives for the development of therapeutic tools for gestational diabetes. ABSTRACT: We investigated the kinetics of glucose-induced insulin secretion and their relationship with [Ca2+ ]i and the expression of protein from exocytotic machinery in islets from recovered pregnant and long-term protein-deficient pregnant rats. Isolated islets were evaluated from control-fed pregnant (CP), protein-deficient pregnant (DP), control-fed non-pregnant (CNP) and protein-deficient non-pregnant (DNP) female adult rats, and from protein-deficient pregnant (RP) and non-pregnant (RNP) rats that were recovered after weaning. The insulin responses to glucose during the first phase of secretion were higher in RP than in CP groups, and both were higher than in the DP group. Islets from RP rats displayed a rapid increase in insulin release (first phase), followed by a plateau that was maintained thereafter. The [Ca2+ ]i in islets from the protein-deficient groups was lower than in the control groups, and both were lower than in the RP and RNP groups. SNAP-25 was increased in islets from pregnant rats independently of their nutritional status, and the syntaxin-1A content was reduced in islets from the RP rats compared with the RNP rats. The VAMP2 content was similar among the groups. Thus, protein restriction during intrauterine life and lactation increased insulin secretion during pregnancy, attributable, in part, to increased [Ca2+ ]i , and independent of an alteration of expression of SNARE proteins.

Nutritional recovery from a low-protein diet during pregnancy does not restore the kinetics of insulin secretion and Ca2+ or alterations in the cAMP/PKA and PLC/PKC pathways in islets from adult rats.

We investigated the insulin release induced by glucose, the Ca2+ oscillatory pattern, and the cyclic AMP (cAMP)/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC) pathways in islets from adult rats that were reared under diets with 17% protein (C) or 6% protein (LP) during gestation, suckling, and after weaning and in rats receiving diets with 6% protein during gestation and 17% protein after birth (R). First-phase glucose-induced insulin secretion was reduced in LP and R islets, and the second phase was partially restored in the R group. Glucose stimulation did not modify intracellular Ca2+ concentration, but it reduced the Ca2+ oscillatory frequency in the R group compared with the C group. Intracellular cAMP concentration was higher and PKA-Cα expression was lower in the R and LP groups compared with the C group. The PKCα content in islets from R rats was lower than that in C and LP rats. Thus, nutritional recovery from a low-protein diet during fetal life did not repair the kinetics of insulin release, impaired Ca2+ handling, and altered the cAMP/PKA and PLC/PKC pathways.

Segunda opinião formativa: o que é e como orientar o cuidado de uma criança com brotoeja?

Brotoeja é o nome popular da miliária, uma dermatite inflamatória causada pela obstrução das glândulas sudoríparas, que impede a saída do suor. As bolhas podem ser pequenas, transparentes e sem sinal de inflamação. Quando observamos pus, provavelmente, está ocorrendo uma infecção bacteriana secundária. O tratamento da brotoeja leva em conta as características das lesões, o local onde se instalaram e a idade do paciente.

Segunda opinião formativa: como proceder na UBS com uma gestante que relata ser Rh negativo apenas na sua 5ª gestação?

A Doença Hemolítica Perinatal (DHP) caracteriza-se pela hemólise fetal, com suas múltiplas e graves repercussões sobre a vitalidade do feto. É imprescindível que o diagnóstico se antecipe à Doença Hemolítica Perinatal (DHP). É importante avaliar se houve alguma das principais formas de exposição materna ao sangue fetal,para que intervenções e medidas de prevenção sejam realizadas.

Segunda opinião formativa: quais os sintomas envolvidos e como manejar a síndrome da respiração oral?

O paciente respirador oral apresenta semi-obstrução nasal intermitente ou persistente, respiração ruidosa e roncos. A dificuldade respiratória varia entre formas mais leves de ronco até quadros de apneia. A síndrome da respiração oral se inclui dentro dos distúrbios respiratórios obstrutivos do sono. Associa-se com vários problemas na saúde e com a piora da qualidade de vida na infância e adolescência.

Segunda opinião formativa: qual importância da hidratação para os casos com arboviroses, mesmo que não apresentem diarreia e vômito?

A Hidratação é recomendada para pacientes com suspeita de dengue, chikungunya e zika (arboviroses) com a finalidade de prevenir o surgimento de desidratação e ajudar na recuperação do paciente.

Segunda opinião formativa: quais as orientações de enfermagem para crianças com alguma alergia ou intolerância alimentar?

Apesar do risco das reações alérgicas serem graves e mesmo fatais, até o momento, o método mais efetivo para a prevenção dos sintomas e tratamento tanto das alergias como das intolerâncias alimentares é a retirada do alimento "agressor" da dieta, sendo necessário substituí-los por alimentos tolerados. A completa eliminação do alimento alergênico é a única forma comprovada, atualmente disponível de tratamento.

Segunda opinião formativa: a notificação de casos de HIV é obrigatória?

Os profissionais de saúde dos serviços públicos e privados devem notificar regularmente às autoridades de saúde os casos de infecção por HIV, a partir de confirmação de diagnóstico desde 2014. Os profissionais de saúde terão que notificar todos os casos de aids em adultos e crianças, mesmo que tenham sido comunicados anteriormente com infecção pelo HIV. A partir de agora, terão que ser notificados os portadores por HIV e as pessoas que vivem com AIDS.

Segunda opinião formativa: que condutas adotar para uma paciente gestante com quadro de nefrolitíase?

O diagnóstico de nefrolitíase assintomática durante a gestação não requer medidas adicionais, apenas o seguimento do pré-natal normal. Contudo, quando ocorre cólica renal ou complicações decorrentes da nefrolitíase, medidas adicionais tornam-se necessárias. Nestes eventos, mais comuns nos últimos meses de gestação, há particularidades relacionadas ao quadro clínico, diagnóstico e tratamentos específicos.

Segunda opinião formativa: como deve ser feito o manejo do uso de corticoide em casos de febre chikungunya?

Os corticosteroides são contraindicados na fase aguda da febre Chikungunya e a medicação padrão para uso oral é a prednisona. Nas fases subaguda e crônica, o uso de corticóides está indicado apenas para os casos com dor articular não responsiva a AINE (Anti-Inflamatórios Não Esteroidais) e analgésicos, em pacientes com dor moderada a intensa, poliarticular e debilitante. Para os casos onde haja evidência de processo inflamatório articular, com dor associada a edema, pode ser iniciado corticosteroide na forma oral.

Segunda opinião formativa: qual a diferença entre intolerância a lactose e alergia a leite?

A alergia ao leite envolve mecanismos imunológicos contra as proteínas do leite enquanto que, a intolerância é um processo secundário à deficiência da enzima responsável pela digestão do principal açúcar do leite, a lactose. É muito importante a consulta com o médico da equipe de saúde da família que poderá solicitar exames específicos para auxiliar o diagnóstico.

Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation.

Low-protein diet disrupts the crosstalk between the PKA and PKC signaling pathways in isolated pancreatic islets.

Protein restriction in the early stages of life can result in several changes in pancreatic function. These alterations include documented reductions in insulin secretion and in cytoplasmic calcium concentration [Ca(2+)]i. However, the mechanisms underlying these changes have not been completely elucidated and may result, in part, from alterations in signaling pathways that potentiate insulin secretion in the presence of glucose. Our findings suggest that protein restriction disrupts the insulin secretory synergism between Cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and Ca(2+)-dependent protein kinase C (PKC) in isolated islets. Western blot analysis demonstrated reduced levels of both phospho-cAMP response element-binding protein (phospho-CREB) at Ser-133 and substrates phosphorylated by PKCs (Phospho-(Ser) PKC substrate), suggesting that PKA and PKC activity was impaired in islets from rats fed a low-protein diet (LP). cAMP levels and global Ca(2+) entry were also reduced in LP islets. In summary, our findings showed that protein restriction altered the crosstalk between PKA and PKC signaling pathways, resulting in the alteration of secretory synergism in isolated islets.

A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets.

BACKGROUND: Gap junctions between ß-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between ß-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1-15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls. RESULTS: The low-protein diet reduced the levels of connexin 36 and ß-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser(279/282)]-connexin 43, and it decreased the levels of connexin 36, ß-catenin and beta-actin mRNA as well as the levels of connexin 36 and ß-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser(279/282)]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status. CONCLUSION: Short-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion.

A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets

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