The incidence of obesity is increasing rapidly all over the world and results in numerous health detriments, including disruptions reproduction. However, mechanisms by which excess body fat interferes with reproductive functions are still not fully understood. After weaning, female rats were treated a cafeteria diet or chow (control group). Biometric metabolic parameters evaluated adulthood. Reproductive parameters, estradiol, progesterone, LH prolactin during proestrus afternoon, sexual...

Cachexia is one of the most important causes cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss muscle tissue, although few studies have examined effect this type nutritional supplementation on metabolism tumour-bearing host. Therefore, present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues Walker-256 rats (providing an experimental model cachexia).After 21 days...

Patients with type 1 diabetes (T1D) suffer from insufficient functional β-cell mass, which results infiltration of inflammatory cells and cytokine-mediated death. Previous studies demonstrated the beneficial effects agonists growth hormone-releasing hormone receptor (GHRH-R), such as MR-409 on preconditioning islets in a transplantation model. However, therapeutic potential protective mechanisms GHRH-R models T1D have not been explored. Using vitro vivo T1D, we assessed propertie GHRH...

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic morphofunctional regulation body nutrient homeostasis 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg weight) or saline [control (CTL) group] during first 5 days life. At 30 age, both groups were submitted to sham-surgery (CTL groups) subdiaphragmatic vagotomy (Cvag Mvag groups). presented...

Elevation of glucagon levels and increase in α-cell mass are associated with states hyperglycemia diabetes. Our previous studies have highlighted the role nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls secretion mass. In current we investigated effects activation by conditional deletion mTORC1 inhibitor, TSC2, α-cells (αTSC2KO). We showed is sufficient to induce chronic hyperglucagonemia as a result proliferation, cell size, expansion. Hyperglucagonemia αTSC2KO was...

Maintenance of pancreatic β-cell mass and function is fundamental to glucose homeostasis prevent diabetes. The PI3 K-Akt-mTORC1 pathway critical for β-cells function, while PDX1 has been implicated in development, maturation, function. Here we tested whether Akt signaling requires expression regulate mass, proliferation, homeostasis. In order address that, crossed a mouse model overexpressing constitutively active mutant (β-caAkt) with mice lacking one allele PDX1gene (β-caAkt/pdx1+/-)....

Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role amplifying pathway (AMP PATH) in β cells malnourished obese mice. C57Bl-6 mice were fed a control (C) or low-protein diet (R). The groups then high-fat (CH and RH). AMP PATH contribution to insulin secretion was upon incubating islets with diazoxide KCl. CH RH displayed increased glucose intolerance, resistance glucose-stimulated secretion. Only showed higher PATH. mitochondrial membrane potential...

PURPOSE: To evaluate the effects of duodenal-jejunal bypass (DJB) on serum and hepatic profiles obese rats fed a western diet (WD). METHODS: Twenty eight male Wistar were standard rodent chow (CTL group) or WD ad libitum. After 10 weeks, submitted to sham (WD SHAM) DJB). Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, TyG, lipids profile analyses evaluated two months after surgery. RESULTS: The SHAM group presented greater obesity, hyperglycemia, hyperinsulinemia, insulin...

Elevation of glucagon levels and increase in α cell proliferation is associated with states hyperglycemia diabetes. A better understanding the molecular mechanisms governing secretion could have major implications for abnormal responses to hypoglycemia patients diabetes provide novel avenues management. Using mice inducible induction Rheb1 cells (αRhebTg mice), we showed that short-term activation mTORC1 signaling sufficient induce hyperglucagonemia through increased secretion....

Nutrient malnutrition, during the early stages of development, may facilitate onset metabolic diseases later in life. However, consequences nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers mitochondrial function gastrocnemius muscle protein-restricted mice fed an HFD until adulthood. Male C57BL/6 were control (14% protein-control diet) or (6% for 6 weeks. Afterward, received...

Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in clearance, β-cell dysfunction. However, studies indicate that, for T2D development, disruptions glucagon physiology also occur. Herein, we investigated the involvement of impaired glycemia control monosodium glutamate (MSG)-obese mice. Male Swiss mice were subcutaneously injected daily, during first 5 days after birth, with MSG (4 mg/g body weight [BW])...

G protein–coupled receptors (GPCRs) are important modulators of glucose-stimulated insulin secretion, essential for maintaining energy homeostasis. Here we investigated the role Gβ5–R7, a protein complex consisting atypical β subunit Gβ5 and regulator signaling R7 family. Using mouse insulinoma MIN6 cell line pancreatic islets, effects 5 (Gnb5) knockout on secretion. Consistent with previous work, Gnb5 diminished secretion evoked by muscarinic cholinergic agonist Oxo-M. We found that also...

The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the mTORC1 function adaptation β-cells resistant state. Here, we use mice with heterozygous deletion (βraHet) assess whether reduced is critical for normal conditions or during high-fat diet (HFD). Deletion a allele showed no differences at metabolic level, islets morphology, fed regular chow. Surprisingly, only one...

The aim of this study was to investigate the effect subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early life, followed exposure high-fat adulthood. Weaned 30-day-old C57Bl/6 mice were submitted (6% protein). After 4 weeks, distributed into three groups: LP group, which continued receiving diet; + HF started receive HFvag underwent also kept at diet. Glucose-stimulated secretion (GSIS) isolated islets,...

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans rodents. Since these strategies fail treat hypothalamic obesity, we have assessed possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism morphophysiology pancreatic islets, (HyO) rats. During first 5 days life, male Wistar rats received subcutaneous injections monosodium glutamate (4 g/kg body weight,...

In both T1DM and T2DM, glucagon secretion is impaired no longer inhibited by hyperglycemia nor insulin, suggesting a defect in the insulin signaling via IRS/PI3k/Akt on pancreatic α-cells. Using mouse model with constitutive activation of Akt α-cells (αpCall), we investigated impact at different glucose concentrations. The αpCall mice exhibited lower body weight hypoglycemia early life. Given mosaic expression transgene α-cells, displayed normal homeostasis, glucagon, secretion. isolated...