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Propolis is a natural resinous mixture produced by honeybees with numerous biological activities. Considering the recently reported potential of propolis as an adjuvant in COVID-19 treatment, a methodology for the fractionation of the hexane extract of Brazilian green propolis (HEGP) was developed for the obtention of prenylated biomarkers by countercurrent chromatography. The inhibition of the interaction between the receptor binding domain (RBD) of spike and ACE2 receptor was evaluated by the Lumitáµá´¹ immunoassay. Fractionation of HEGP was performed by both normal (CCC1 and CCC2, with extended elution) and reversed (CCC3) phase elution-extrusion modes with the solvent system hexane-ethanol-water 4:3:1. The normal elution mode of CCC1 (471 mg HEGP in a 80 mL column volume, 1.6 mm id) was scaled-up (CCC5, 1211 mg HEGP in a 112 mL column volume, 2.1 mm id), leading to the isolation of 89.9 mg of artepillin C, 1; 52.7 mg of baccharin, 2; and 26.6 mg of chromene, with purities of 93 %, 83 % and 88 %, respectively, by HPLC-PDA. Among the isolated compounds, artepillin C, 1, and baccharin, 2, presented the best results in the Lumitáµá´¹ immunoassay, showing 67% and 51% inhibition, respectively, at the concentration of 10 µM. This technique proved to be of low operational cost and excellent reproducibility.
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The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections.
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Peptídeos Antimicrobianos , Venenos de Vespas , Venenos de Vespas/farmacologia , Venenos de Vespas/química , Peptídeos/químicaRESUMO
Bacterial inoculants have been used in agriculture to improve plant performance. However, laboratory and field requirements must be completed before a candidate can be employed as an inoculant. Therefore, this study aimed to evaluate the parameters for inoculant formulation and the potential of Bacillus subtilis (B70) and B. pumilus (B32) to improve phosphorus availability in maize (Zea mays L.) crops. In vitro experiments assessed the bacterial ability to solubilize and mineralize phosphate, their adherence to roots, and shelf life in cassava starch (CS), carboxymethyl cellulose (CMC), peat, and activated charcoal (AC) stored at 4 °C and room temperature for 6 months. A field experiment evaluated the effectiveness of strains to increase the P availability to plants growing with rock phosphate (RP) and a mixture of RP and triple superphosphate (TS) and their contribution to improving maize yield and P accumulation in grains. The B70 was outstanding in solubilizing RP and phytate mineralization and more stable in carriers and storage conditions than B32. However, root adherence was more noticeable in B32. Among carriers, AC was the most effective for preserving viable cell counts, closely similar to those of the initial inoculum of both strains. Maize productivity using the mixture RPTS was similar for B70 and B32. The best combination was B70 with RP, which improved the maize yield (6532 kg ha-1) and P accumulation in grains (15.95 kg ha-1). Our results indicated that the inoculant formulation with AC carrier and B70 is a feasible strategy for improving phosphorus mobilization in the soil and maize productivity.
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Bacillus , Fosfatos , Fosfatos/metabolismo , Bacillus/metabolismo , Raízes de Plantas/microbiologia , Fósforo/metabolismo , Bacillus subtilis/metabolismo , Solo , Zea mays/microbiologiaRESUMO
Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.
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Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.
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Throughout evolution, plants have developed a highly complex defense system against different threats, including phytopathogens. Plant defense depends on constitutive and induced factors combined as defense mechanisms. These mechanisms involve a complex signaling network linking structural and biochemical defense. Antimicrobial and pathogenesis-related (PR) proteins are examples of this mechanism, which can accumulate extra- and intracellular space after infection. However, despite their name, some PR proteins are present at low levels even in healthy plant tissues. When they face a pathogen, these PRs can increase in abundance, acting as the first line of plant defense. Thus, PRs play a key role in early defense events, which can reduce the damage and mortality caused by pathogens. In this context, the present review will discuss defense response proteins, which have been identified as PRs, with enzymatic action, including constitutive enzymes, ß-1,3 glucanase, chitinase, peroxidase and ribonucleases. From the technological perspective, we discuss the advances of the last decade applied to the study of these enzymes, which are important in the early events of higher plant defense against phytopathogens.
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Due to inadequate treatment and incorrect management, wastewater with dyes has a great toxic potential as an environmental liability, representing a major concern. In this context, this work aims to investigate the potential application of nanostructured powdery systems (nanocapsules and liposomes) in the photodegradation of Rhodamine B (RhB) dye, under UV and visible irradiation. Curcumin nanocapsules and liposomes containing ascorbic acid and ascorbyl palmitate were prepared, characterized, and dried using the spray drying technique. The drying processes of the nanocapsule and the liposome showed yields of 88% and 62%, respectively, and, after aqueous resuspension of the dry powders, it was possible to recover the nanocapsule size (140 nm) and liposome size (160 nm). The dry powders were characterized by Fourier transform infrared spectroscopy (FTIR), N2 physisorption at 77 K, X-ray diffraction (XRD), and diffuse reflectance spectroscopy (DRS-UV). Under UV irradiation, 64.8% and 58.48% of RhB were removed with nanocapsules and liposomes, respectively. While under visible radiation, nanocapsules and liposomes were able to degrade 59.54% and 48.79% of RhB, respectively. Under the same conditions, commercial TiO2 showed degradation of 50.02% (UV) and 42.14% (visible). After 5 cycles of reuse, there was a decrease of about 5% for dry powders under UV irradiation and 7.5% under visible irradiation. Therefore, the nanostructured systems developed have potential application in heterogeneous photocatalysis for the degradation of organic pollutants, such as RhB, as they demonstrated superior photocatalytic performance to commercial catalysts (nanoencapsulated curcumin > ascorbic acid and ascorbyl palmitate liposomal > TiO2).
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Curcumina , Nanocápsulas , Pós , Corantes , Lipossomos , Ácido AscórbicoRESUMO
OBJECTIVES: Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and severe asthma would have a higher prevalence of obstructive sleep apnea. METHODS: Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test. RESULTS: The authors studied 80 consecutive patients, 7-18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity. CONCLUSIONS: Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.
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Asma , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Masculino , Adolescente , Humanos , Criança , Feminino , Estudos Transversais , Prevalência , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Asma/complicações , Asma/epidemiologia , Fatores de RiscoRESUMO
Abstract Objectives: Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and severe asthma would have a higher prevalence of obstructive sleep apnea. Methods: Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test. Results: The authors studied 80 consecutive patients, 7-18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity. Conclusions: Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.
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Pancreatic islet beta cells are essential for maintaining glucose homeostasis. To understand the impact of aging on beta cells, we performed meta-analysis of single-cell RNA sequencing datasets, transcription factor (TF) regulon analysis, high-resolution confocal microscopy, and measured insulin secretion from nondiabetic donors spanning most of the human life span. This revealed the range of molecular and functional changes that occur during beta cell aging, including the transcriptional deregulation that associates with cellular immaturity and reorganization of beta cell TF networks, increased gene transcription rates, and reduced glucose-stimulated insulin release. These alterations associate with activation of endoplasmic reticulum (ER) stress and autophagy pathways. We propose that a chronic state of ER stress undermines old beta cell structure function to increase the risk of beta cell failure and type 2 diabetes onset as humans age.
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Gossypium hirsutum L. represents the best cotton species for fiber production, thus computing the largest cultivated area worldwide. Meloidogyne incognita is a root-knot nematode (RKN) and one of the most important species of Meloidogyne genus, which has a wide host range, including cotton plants. Phytonematode infestations can only be partially controlled by conventional agricultural methods, therefore, more effective strategies to improve cotton resistance to M. incognita disease are highly desirable. The present study employed functional genomics to validate the involvement of two previously identified candidate genes, encoding dirigent protein 4-GhDIR4 and peroxiredoxin-2-GhPRXIIB, in cotton defense against M. incognita. Transgenic A. thaliana plant lines overexpressing GhDIR4 and GhPRXIIB genes were generated and displayed significantly improved resistance against M. incognita infection in terms of female nematode abundance in the roots when compared to wild-type control plants. For our best target-gene GhDIR4, an in-silico functional analysis, including multiple sequence alignment, phylogenetic relationship, and search for specific protein motifs unveiled potential orthologs in other relevant crop plants, including monocots and dicots. Our findings provide valuable information for further understanding the roles of GhDIR and GhPRXIIB genes in cotton defense response against RKN nematode. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03282-4.
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AIMS: Synthetic glucocorticoids, including dexamethasone (DEX), are clinically prescribed due to their immunoregulatory properties. In excess they can perturb glucose homeostasis, with individuals predisposed to glucose intolerance more sensitive to these negative effects. While DEX is known to negatively impact ß-cell function, it is unclear how. Hence, our aim was to investigate the effect of DEX on ß-cell function, both alone and in combination with a diabetogenic milieu in the form of elevated glucose and palmitate. MAIN METHODS: Human pancreatic EndoC-ßH1 cells were cultured in the presence of high glucose and palmitate (glucolipotoxicity) and/or a pharmacological concentration of DEX, before functional and molecular analyses. KEY FINDINGS: Either treatment alone resulted in reduced insulin content and secretion, while the combination of DEX and glucolipotoxicity promoted a strong synergistic effect. These effects were associated with reduced insulin biosynthesis, likely due to downregulation of PDX1, MAFA, and the proinsulin converting enzymes, as well as reduced ATP response upon glucose stimulation. Genome-wide DNA methylation analysis found changes on PDE4D, MBNL1 and TMEM178B, all implicated in ß-cell function, after all three treatments. DEX alone caused very strong demethylation of the glucocorticoid-regulated gene ZBTB16, also known to influence the ß-cell, while the combined treatment caused altered methylation of many known ß-cell regulators and diabetes candidate genes. SIGNIFICANCE: DEX treatment and glucolipotoxic conditions separately alter the ß-cell epigenome and function. The combination of both treatments exacerbates these changes, showing that caution is needed when prescribing potent glucocorticoids in patients with dysregulated metabolism.
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Glucocorticoides , Células Secretoras de Insulina , Trifosfato de Adenosina/metabolismo , Dexametasona/metabolismo , Dexametasona/toxicidade , Epigenoma , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Glucose/metabolismo , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Palmitatos/farmacologia , Proinsulina/metabolismo , Proinsulina/farmacologiaRESUMO
Nisin was encapsulated in silica through sol-gel process by acid-catalyzed routes. The silica xerogels were characterized through nitrogen adsorption isotherms, small-angle X-ray scattering (SAXS), zeta potential, X-ray diffraction (XRD), scanning electron microscopy (SEM), diffuse reflectance spectroscopy (DRS), and Fourier transform infrared spectroscopy (FTIR). SAXS results showed that the particle diameters in a second level of aggregation varied from 4.78 to 5.86 nm. Zeta potential of silica particles were from -9.6 to -25.3 mV, while the surface area and pore diameters ranged from 216 to 598 m2 g-1 and 2.53 to 2.90 nm, respectively, indicating the formation of mesoporous nanostructures. Nisin retained the antimicrobial activity against all microorganisms tested after encapsulation in silica materials. These novel silica-based structures can be valuable carriers for nisin delivery in food systems.
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Bacteriocinas , Nisina , Espalhamento a Baixo Ângulo , Dióxido de Silício , Difração de Raios XRESUMO
AIMS: Glucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism. MATERIALS AND METHODS: Adult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses. KEY FINDINGS: Dexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances. SIGNIFICANCE: Coadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats.
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Dexametasona/efeitos adversos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Fosfato de Sitagliptina/administração & dosagem , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Teste de Tolerância a Glucose , Masculino , Ratos , Ratos WistarRESUMO
COVID-19 implications are still a threat to global health. In the face of this pandemic, food and nutrition are key issues that can boost the immune system. The bioactivity of functional foods and nutrients (probiotics, prebiotics, water- and fat-soluble vitamins, minerals, flavonoids, glutamine, arginine, nucleotides, and PUFAs) contributes to immune system modulation, which establishes the status of nutrients as a factor of immune competence. These foods can contribute, especially during a pandemic, to the minimization of complications of SARS-CoV-2 infection. Therefore, it is important to support the nutritional strategies for strengthening the immune status, associated with good eating habits, as a way to confront COVID-19.
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COVID-19/imunologia , Alimento Funcional , Imunomodulação , Nutrientes/administração & dosagem , Estado Nutricional/imunologia , Arginina , Ácidos Graxos Ômega-3 , Glutamina , Humanos , Fenóis , Prebióticos , Probióticos , SARS-CoV-2 , OligoelementosRESUMO
Since prenatal glucocorticoids (GC) excess increases the risk of metabolic dysfunctions in the offspring and its effect on ß-cell recovery capacity remains unknown we investigated these aspects in offspring from mice treated with dexamethasone (DEX) in the late pregnancy. Half of the pups were treated with streptozotocin (STZ) on the sixth postnatal day (PN). Functional and molecular analyses were performed in male offspring on PN25 and PN225. Prenatal DEX treatment resulted in low birth weight. At PN25, both the STZ-treated offspring developed hyperglycemia and had lower ß-cell mass, in parallel with higher α-cell mass and glucose intolerance, with no impact of prenatal DEX on such parameters. At PN225, the ß-cell mass was partially recovered in the STZ-treated mice, but they remained glucose-intolerant, irrespective of being insulin sensitive. Prenatal exposition to DEX predisposed adult offspring to sustained hyperglycemia and perturbed islet function (lower insulin and higher glucagon response to glucose) in parallel with exacerbated glucose intolerance. ß-cell-specific knockdown of the Hnf4α in mice from the DS group resulted in exacerbated glucose intolerance. We conclude that high GC exposure during the prenatal period exacerbates the metabolic dysfunctions in adult life of mice exposed to STZ early in life, resulting in a lesser ability to recover the islets' function over time. This study alerts to the importance of proper management of exogenous GCs during pregnancy and a healthy postnatal lifestyle since the combination of adverse factors during the prenatal and postnatal period accentuates the predisposition to metabolic disorders in adult life.
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Dexametasona/toxicidade , Glucocorticoides/toxicidade , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Dexametasona/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Teste de Tolerância a Glucose , Insulina/farmacologia , Camundongos , Neoplasias Experimentais , Gravidez , Efeitos Tardios da Exposição Pré-Natal , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Antibiotics are essential molecules for the treatment and prophylaxis of many infectious diseases. However, drugs that combat microbial infections can become a human health threat due to their high and often indiscriminate consumption, considered one of the factors of antimicrobial resistance (AMR) emergence. The AMR crisis, the decrease in new drug development by the pharmaceutical industry, and reduced economic incentives for research have all reduced the options for treating infections, and new strategies are necessary, including the return of some traditional but "forgotten" antibiotics. However, prescriptions for these older drugs including nitrofurantoin and oral fosfomycin, have been based on the results of pioneer studies, and the limited knowledge generated 50-70 years ago may not be enough. To avoid harming patients and further increasing multidrug resistance, systematic evaluation is required, mainly for the drugs prescribed for community-acquired infections, such as urinary tract infections (UTI). Therefore, this review has the objective of reporting the use of two classic drugs from the nitrofuran and phosphonic acid classes for UTI control nowadays. Furthermore, we also explore new approaches used for these antibiotics, including new combination regimes for spectral amplification, and the prospects for reducing bacterial resistance in the fight against bacteria responsible for UTI.
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Antibacterianos/farmacologia , Fosfomicina/farmacologia , Nitrofurantoína/farmacologia , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Desenvolvimento de Medicamentos/tendências , Indústria Farmacêutica/tendências , Farmacorresistência Bacteriana Múltipla , Fosfomicina/administração & dosagem , Humanos , Nitrofurantoína/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologiaRESUMO
AIMS: Pregnancy is associated with the development of a transitory insulin resistance that parallels with the upregulation of pancreatic ß-cell function and mass. These metabolic adaptations guarantee the higher insulin demand, but there is no evidence of whether insulin clearance contributes to this process. Thus, we investigated some of the hepatic parameters related to insulin clearance during rat pregnancy. We also investigated some molecular parameters in the hypothalamus. MAIN METHODS: We evaluated the body mass and food intake, insulin sensitivity, ß- and α-cell masses, insulin clearance based on an exogenous insulin load, hepatic insulin-degrading enzyme (IDE) activity, and hepatic and hypothalamic protein content of IDE and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) in three periods of gestation in Wistar rats. KEY FINDINGS: In the first week of pregnancy, both insulin sensitivity and clearance increased, a pattern that inverted in the third week of gestation (reduced insulin sensitivity and clearance). Diminished insulin clearance was associated with lower hepatic IDE activity and higher pancreatic ß- and α-cell masses. No alteration in the hepatic IDE and CEACAM protein content was observed throughout pregnancy, but hypothalamic IDE protein content was significantly reduced in the late gestation period. SIGNIFICANCE: In conclusion, elevated insulin demand in the late period of gestation occurs not only as a result of increased ß-cell mass and function but also by a potential reduction in hepatic insulin clearance. Knowing this physiological process may be valuable when considering gestational diabetes mellitus results from a failure in insulin supply during pregnancy.