Production and Characterization of k-Carrageenan Films Incorporating Cymbopogon winterianus Essential Oil as New Food Packaging Materials.

The global production of synthetic plastics from petroleum-based raw ingredients exceeds 150 million metric tons. The environment is threatened by tons of plastic waste, thus endangering wildlife and the public's health. These consequences increased the interest in biodegradable polymers as potential substitutes for traditional packaging materials. This study aimed to produce and characterize k-carrageenan films incorporating Cymbopogon winterianus essential oil, in which citronellal was determined to be the major compound (41.12%). This essential oil presented remarkable antioxidant activity, as measured through DPPH (IC50 = 0.06 ± 0.01%, v/v; AAI = 85.60 ± 13.42) and ß-carotene bleaching (IC50 = 3.16 ± 0.48%, v/v) methods. The essential oil also showed antibacterial properties against Listeria monocytogenes LMG 16779 (diameter of inhibition zone = 31.67 ± 5.16 mm and MIC = 8 µL/mL), which were also observed when incorporated in the k-carrageenan films. Moreover, scanning electron microscopy showed the reduction of the biofilms of this bacterium, and even its inactivation, due to visible destruction and loss of integrity when the biofilms were created directly on the developed k-carrageenan films. This study also revealed the quorum sensing inhibition potential of Cymbopogon winterianus essential oil (diameter of violacein production inhibition = 10.93 ± 0.81 mm), where it could impede intercellular communication and, hence, lower violacein synthesis. The produced k-carrageenan films were transparent (>90%) and slightly hydrophobic (water contact angle > 90°). This work demonstrated the viability of using Cymbopogon winterianus essential oil to produce k-carrageenan bioactive films as new food packaging materials. Future work should focus on the scale-up production of these films.

Computational Simulation Tools to Support the Tissue Paper Furnish Management: Case Studies for the Optimization of Micro/Nano Cellulose Fibers and Polymer-Based Additives.

Tissue paper production frequently combines two main types of raw materials: cellulose fibers from renewable sources and polymer-based additives. The development of premium products with improved properties and functionalities depends on the optimization of both. This work focused on the combination of innovative experimental and computational strategies to optimize furnish. The main goal was to improve the functional properties of the most suitable raw materials for tissue materials and develop new differentiating products with innovative features. The experimental plan included as inputs different fiber mixtures, micro/nano fibrillated cellulose, and biopolymer additives, and enzymatic and mechanical process operations. We present an innovative tissue paper simulator, the SimTissue, that we have developed, to establish the correlations between the tissue paper process inputs and the end-use paper properties. Case studies with industrial interest are presented in which the tissue simulator was used to design tissue paper materials with different fiber mixtures, fiber modification treatments, micro/nano fibrillated cellulose, and biopolymer formulations, and to estimate tissue softness, strength, and absorption properties. The SimTissue was able to predict and optimize a broader range of formulations containing micro/nanocellulose fibers, biopolymer additives, and treated-fiber mixtures, saving laboratory and industrial resources.

An Innovative Computational Strategy to Optimize Different Furnish Compositions of Tissue Materials Using Micro/Nanofibrillated Cellulose and Biopolymer as Additives.

The furnish management of tissue materials is fundamental to obtain maximum quality products with a minimum cost. The key fiber properties and fiber modification process steps have a significant influence on the structural and functional properties of tissue paper. In this work, two types of additives, a commercial biopolymer additive (CBA) that replaces the traditional cationic starch and micro/nanofibrillated cellulose (CMF), were investigated. Different formulations were prepared containing eucalyptus fibers and softwood fibers treated mechanically and enzymatically and both pulps with these two additives incorporated independently and simultaneously with drainage in the tissue process range. The use of these additives to reduce the percentage of softwood fibers on tissue furnish formulations was investigated. The results indicated that a maximum of tensile strength was obtained with a combination of both additives at the expense of softness and water absorbency. With a reduction of softwood fibers, the incorporation of additives increased the tensile strength and water absorbency with a slight decrease in HF softness compared with a typical industrial furnish. Additionally, a tissue computational simulator was also used to predict the influence of these additives on the final end-use properties. Both additives proved to be a suitable alternative to reduce softwood fibers in the production of tissue products, enhancing softness, strength and absorption properties.

Application of Solidago chilensis and laser improved the repair of burns in diabetic rats.

BACKGROUND: The repair of burns in diabetic patients is a clinical problem. It is relevant to study alternative therapies that can improve the healing process. Our aim was to investigate the effects of Solidago chilensis associated or not with laser on burns in diabetic rats. METHODS: The animals were divided in four groups (n = 30): C- without treatment; S- S. chilensis extract; L-laser irradiated; LS- laser and S. chilensis. In 7, 14 and 21 days samples were collected after the injury to structural, morphometric and molecular analysis. RESULTS: Our results demonstrate the association of S. chilensis and laser reduced the inflammatory infiltrate and favored the angiogenesis. In the groups treated only with laser or with the plant extract showed higher levels of VEGF. The low-level laser therapy (LLLT) promoted higher collagen I and reduction of collagen III. It was also observed higher MMP-2 activation and a decreasing of the active isoform of MMP-9 in the S, L and LS groups. CONCLUSIONS: The treatments improved the repair of burns in diabetic rats, since it reduced the inflammatory infiltrate and favored the collagen organization presenting similar effects in the burn repair of the diabetics.

Experimental 3D fibre data for tissue papers applications.

Tissue paper consumption has been growing for the past years, with a forecasted increase in demand for premium products. Premium tissue paper products are obtained with a balance among softness, strength, and absorption properties, optimized for each kind of tissue paper. These properties are influenced by the three-dimensional structure, made from the spatial distribution of cellulose fibres. To our knowledge, the efforts made to date to improve the softness, strength and absorption properties have overlooked the 3D structure. There is an absence of 3D experimental data in the literature for the simultaneous characterization of individual eucalyptus fibres and the paper structure made from these fibres. The 2D fibre morphology determination, including fibre length and fibre width, was obtained by an image analysis method for pulp fibre suspensions, using the MorFiⓇ equipment. The third fibre dimension, the fibre thickness morphology in the out-of-plane direction, was obtained using SEM images of non-pressed isotropic laboratory-made paper sheets. The effective fibre thickness morphology, consisting of the fibre wall and lumen, was measured in the paper structure, as this is precisely the key fibre parameter, influencing not only the structure-related properties, such as paper thickness, bulk, and porosity, but also the final end-use properties. The paper structures were produced using an ISO standard adapted method, for tissue paper structures, without pressing, with a basis weight range from 20 to 150 g/m2. These data are important, among other possible uses, for paper property optimization and simulation studies with 3D fibre based simulators.

Characterization data of pulp fibres performance in tissue papers applications.

The data presented in this article are related to the original research paper entitled "Comparative characterization of eucalyptus fibres and softwood fibres for tissue papers applications" available in Materials Letter: X Journal [1]. In this article, six eucalyptus hardwood pulps and six softwood pulps were characterized in terms of morphological, chemical and water-related (by drainability and water retention index) properties. In addition, using these pulps, unpressed laboratory isotropic handsheets were produced with a basis weight of approximately 20 g/m2, similarly to tissue papers. The key properties of tissue papers, namely structural properties, tensile index, absorption, and handfeel softness were analysed in these handsheets.

New Insights on Water Buffalo Genomic Diversity and Post-Domestication Migration Routes From Medium Density SNP Chip Data.

The domestic water buffalo is native to the Asian continent but through historical migrations and recent importations, nowadays has a worldwide distribution. The two types of water buffalo, i.e., river and swamp, display distinct morphological and behavioral traits, different karyotypes and also have different purposes and geographical distributions. River buffaloes from Pakistan, Iran, Turkey, Egypt, Romania, Bulgaria, Italy, Mozambique, Brazil and Colombia, and swamp buffaloes from China, Thailand, Philippines, Indonesia and Brazil were genotyped with a species-specific medium-density 90K SNP panel. We estimated the levels of molecular diversity and described population structure, which revealed historical relationships between populations and migration events. Three distinct gene pools were identified in pure river as well as in pure swamp buffalo populations. Genomic admixture was seen in the Philippines and in Brazil, resulting from importations of animals for breed improvement. Our results were largely consistent with previous archeological, historical and molecular-based evidence for two independent domestication events for river- and swamp-type buffaloes, which occurred in the Indo-Pakistani region and close to the China/Indochina border, respectively. Based on a geographical analysis of the distribution of diversity, our evidence also indicated that the water buffalo spread out of the domestication centers followed two major divergent migration directions: river buffaloes migrated west from the Indian sub-continent while swamp buffaloes migrated from northern Indochina via an east-south-eastern route. These data suggest that the current distribution of water buffalo diversity has been shaped by the combined effects of multiple migration events occurred at different stages of the post-domestication history of the species.

Free-breathing whole-heart 3D cine magnetic resonance imaging with prospective respiratory motion compensation.

PURPOSE: To develop and validate a new prospective respiratory motion compensation algorithm for free-breathing whole-heart 3D cine steady-state free precession (SSFP) imaging. METHODS: In a 3D cine SSFP sequence, 4 excitations per cardiac cycle are re-purposed to prospectively track heart position. Specifically, their 1D image is reconstructed and routed into the scanner's standard diaphragmatic navigator processing system. If all 4 signals are in end-expiration, cine image data from the entire cardiac cycle is accepted for image reconstruction. Prospective validation was carried out in patients (N = 17) by comparing in each a conventional breath-hold 2D cine ventricular short-axis stack and a free-breathing whole-heart 3D cine data set. RESULTS: All 3D cine SSFP acquisitions were successful and the mean scan time was 5.9 ± 2.7 min. Left and right ventricular end-diastolic, end-systolic, and stroke volumes by 3D cine SSFP were all larger than those from 2D cine SSFP. This bias was < 6% except for right ventricular end-systolic volume that was 12%. The 3D cine images had a lower ventricular blood-to-myocardium contrast ratio, contrast-to-noise ratio, mass, and subjective quality score. CONCLUSION: The novel prospective respiratory motion compensation method for 3D cine SSFP imaging was robust and efficient and yielded slightly larger ventricular volumes and lower mass compared to breath-hold 2D cine imaging. Magn Reson Med 80:181-189, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A puzzle used to teach the cardiac cycle.

The aim of the present article is to describe a puzzle developed for use in teaching cardiac physiology classes. The puzzle presents figures of phases of the cardiac cycle and a table with five columns: phases of cardiac cycle, atrial state, ventricular state, state of atrioventricular valves, and pulmonary and aortic valves. Chips are provided for use to complete the table. Students are requested to discuss which is the correct sequence of figures indicating the phases of cardiac cycle. Afterward, they should complete the table with the chips. Students of biology, dentistry, medicine, pharmacy, and nursing graduation courses from seven institutions performed the puzzle evaluation. They were invited to indicate whether the puzzle had been useful for learning about the subject by filling one of four alternatives. Of the students, 4.6% answered that it was not necessary but helped them to confirm what they had learned, 64.5% reported that although they had previously understood the cardiac cycle, the puzzle helped them to solve doubts and promoted a better understanding of it, and 30.9% said that they needed the puzzle to understand the cardiac cycle, without differences among courses, institutions, and course semesters. The results of the present study suggest that a simple and inexpensive puzzle may be useful as an active learning methodology applied after the theoretical lecture, as a complementary tool for studying cardiac cycle physiology.

Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity.

In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through the activation of toll-like receptors 2/4 and endoplasmic reticulum stress to induce cytokine expression in the hypothalamus of rodents. According to our results, long-chain saturated fatty acids activate predominantly toll-like receptor 4 signaling, which determines not only the induction of local cytokine expression but also promotes endoplasmic reticulum stress. Rats fed on a monounsaturated fat-rich diet do not develop hypothalamic leptin resistance, whereas toll-like receptor 4 loss-of-function mutation and immunopharmacological inhibition of toll-like receptor 4 protects mice from diet-induced obesity. Thus, toll-like receptor 4 acts as a predominant molecular target for saturated fatty acids in the hypothalamus, triggering the intracellular signaling network that induces an inflammatory response, and determines the resistance to anorexigenic signals.

TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient--effects on leptin and insulin signaling pathways.

Acting in the hypothalamus, tumor necrosis factor-alpha (TNF-alpha) produces a potent anorexigenic effect. However, the molecular mechanisms involved in this phenomenon are poorly characterized. In this study, we investigate the capacity of TNF-alpha to activate signal transduction in the hypothalamus through elements of the pathways employed by the anorexigenic hormones insulin and leptin. High dose TNF-alpha promotes a reduction of 25% in 12h food intake, which is an inhibitory effect that is marginally inferior to that produced by insulin and leptin. In addition, high dose TNF-alpha increases body temperature and respiratory quotient, effects not reproduced by insulin or leptin. TNF-alpha, predominantly at the high dose, is also capable of activating canonical pro-inflammatory signal transduction in the hypothalamus, inducing JNK, p38, and NFkappaB, which results in the transcription of early responsive genes and expression of proteins of the SOCS family. Also, TNF-alpha activates signal transduction through JAK-2 and STAT-3, but does not activate signal transduction through early and intermediary elements of the insulin/leptin signaling pathways such as IRS-2, Akt, ERK and FOXO1. When co-injected with insulin or leptin, TNF-alpha, at both high and low doses, partially impairs signal transduction through IRS-2, Akt, ERK and FOXO1 but not through JAK-2 and STAT-3. This effect is accompanied by the partial inhibition of the anorexigenic effects of insulin and leptin, when the low, but not the high dose of TNF-alpha is employed. In conclusion, TNF-alpha, on a dose-dependent way, modulates insulin and leptin signaling and action in the hypothalamus.

Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets.

During pregnancy and the perinatal period of life, prolactin (PRL) and other lactogenic substances induce adaptation and maturation of the stimulus-secretion coupling system in pancreatic beta-cells. Since the SNARE molecules, SNAP-25, syntaxin 1, VAMP-2, and synaptotagmins participate in insulin secretion, we investigated whether the improved secretory response to glucose during these periods involves alteration in the expression of these proteins. mRNA was extracted from neonatal rat islets cultured for 5 days in the presence of PRL and from pregnant rats (17th-18th days of pregnancy) and reverse transcribed. The expression of genes was analyzed by semi-quantitative RT-PCR assay. The expression of proteins was analyzed by Western blotting and confocal microscopy. Transcription and expression of all SNARE genes and proteins were increased in islets from pregnant and PRL-treated neonatal rats when compared with controls. The only exception was VAMP-2 production in islets from pregnant rats. Increased mRNA and protein expression of synaptotagmin IV, but not the isoform I, also was observed in islets from pregnant and PRL-treated rats. This effect was not inhibited by wortmannin or PD098059, inhibitors of the PI3-kinase and MAPK pathways, respectively. As revealed by confocal laser microscopy, both syntaxin 1A and synaptotagmin IV were immunolocated in islet cells, including the insulin-containing cells. These results indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion.

Inducible-NOS but not neuronal-NOS participate in the acute effect of TNF-alpha on hypothalamic insulin-dependent inhibition of food intake.

TNF-alpha acts on the hypothalamus modulating food intake and energy expenditure through mechanisms incompletely elucidated. Here, we explore the hypothesis that, to modulate insulin-induced anorexigenic signaling in hypothalamus, TNF-alpha requires the synthesis of NO. TNF-alpha activates signal transduction through JNK and p38 in hypothalamus, peaking at 10(-8) M. This is accompanied by the induction of expression of the inducible and neuronal forms of NOS, in both cases peaking at 10(-12) M. In addition, TNF-alpha stimulates NOS catalytic activity. Pre-treatment with TNF-alpha at a low dose (10(-12) M) inhibits insulin-dependent anorexigenic signaling, and this effect is abolished in iNOS but not in nNOS knockout mice.

Leptin inhibits apoptosis in thymus through a janus kinase-2-independent, insulin receptor substrate-1/phosphatidylinositol-3 kinase-dependent pathway.

The cytokine-like hormone leptin is known to exert important functions on the modulation of immune responses. Some of these effects are dependent on the property of leptin to modulate the apoptosis of thymic cells. In the present study, we used Wistar rats to investigate the molecular mechanisms involved in leptin-dependent control of apoptosis in thymus. Apoptosis was evaluated by flow cytometry and ELISA for nucleosome determination, whereas signal transduction was evaluated by immunoprecipitation, immunoblot, and confocal microscopy. The Ob receptor (ObR) was expressed in most thymic cells and its relative amount reduced progressively during thymocyte maturation. ObR expression was colocalized with Janus kinase (JAK)-2 and signal transducer and activator of transcription-3, and an acute, in vivo, injection of leptin promoted the tyrosine phosphorylation of JAK-2 and the engagement of signal transducer and activator of transcription-3. The treatment with leptin also led to the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and serine phosphorylation of Akt. Chronic treatment with leptin reduced thymic apoptosis, an effect that was not inhibited by the JAK inhibitor AG(490) but was significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY(294002) and an antisense oligonucleotide to IRS-1. Thus, leptin inhibits the apoptosis of thymic cells through a mechanism that is independent of the activation of JAK-2 but depends on the engagement of the IRS-1/phosphatidylinositol 3-kinase pathway.

ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion.

The adaptation of pancreatic islets to pregnancy includes increased beta cell proliferation, expansion of islet mass, and increased insulin synthesis and secretion. Most of these adaptations are induced by prolactin (PRL). We have previously described that in vitro PRL treatment increases ERK3 expression in isolated rat pancreatic islets. This study shows that ERK3 is also upregulated during pregnancy. Islets from pregnant rats treated with antisense oligonucleotide targeted to the PRL receptor displayed a significant reduction in ERK3 expression. Immunohistochemical double-staining showed that ERK3 expression is restricted to pancreatic beta cells. Transfection with antisense oligonucleotide targeted to ERK3 abolished the insulin secretion stimulated by glucose in rat islets and by PMA in RINm5F cells. Therefore, we examined the participation of ERK3 in the activation of a cellular target involved in secretory events, the microtubule associated protein MAP2. PMA induced ERK3 phosphorylation that was companied by an increase in ERK3/MAP2 association and MAP2 phosphorylation. These observations provide evidence that ERK3 is involved in the regulation of stimulus-secretion coupling in pancreatic beta cells.

Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets

During pregnancy and the perinatal period of life, prolactin (PRL) and other lactogenic substances induce adaptation and maturation of the stimulus-secretion coupling system in pancreatic â-cells. Since the SNARE molecules, SNAP-25, syntaxin 1, VAMP-2, and synaptotagmins participate in insulin secretion, we investigated whether the improved secretory response to glucose during these periods involves alteration in the expression of these proteins. mRNA was extracted from neonatal rat islets cultured for 5 days in the presence of PRL and from pregnant rats (17th-18th days of pregnancy) and reverse transcribed. The expression of genes was analyzed by semi-quantitative RT-PCR assay. The expression of proteins was analyzed by Western blotting and confocal microscopy. Transcription and expression of all SNARE genes and proteins were increased in islets from pregnant and PRL-treated neonatal rats when compared with controls. The only exception was VAMP-2 production in islets from pregnant rats. Increased mRNA and protein expression of synaptotagmin IV, but not the isoform I, also was observed in islets from pregnant and PRL-treated rats. This effect was not inhibited by wortmannin or PD098059, inhibitors of the PI3-kinase and MAPK pathways, respectively. As revealed by confocal laser microscopy, both syntaxin 1A and synaptotagmin IV were immunolocated in islet cells, including the insulin-containing cells. These results indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion.

Cross-talk between the insulin and leptin signaling systems in rat hypothalamus.

OBJECTIVE: To investigate whether insulin and leptin share common intracellular signal transduction pathways and to determine whether these hormonal signaling systems modulate each other's action in rat hypothalamus. RESEARCH METHODS AND PROCEDURES: Male Wistar rats were studied after chronic implantation of an intracerebroventricular catheter into the third ventricle. Immunoprecipitation and immunoblotting were used to examine the activation of insulin and leptin signaling molecules in the rat hypothalamus. RESULTS: Insulin alone is able to produce molecular activation of insulin receptor substrates (IRSs)/phosphatidylinositol 3-kinase (PI 3-kinase)/Akt and mitogen-activated protein (MAP) kinase signaling pathways in hypothalamus, whereas leptin alone activates MAP kinase and IRSs/PI 3-kinase signaling with no effect on Akt. Combined infusion of leptin and insulin provokes a dual action. There was no quantitative potentialization of any single hormone's action on the elements of the insulin signaling pathway, IRSs/PI 3-kinase/Akt, and MAP kinase. Conversely, leptin plus insulin leads to quantitative potentialization of molecular signaling through the Janus kinase/signal transducer and activator of transcription pathway. DISCUSSION: We provide evidence for a convergence of leptin and insulin signaling at the level of IRSs-PI 3-kinase and a divergence at the level of Akt. Moreover, our results indicate a direct and positive cross-talk between insulin and leptin at the level of Janus kinase 2 and signal transducer and activator of transcription 3 tyrosine phosphorylation. This mechanism may serve to potentiate the activity of both insulin and leptin pathways and to increase stimulation in physiological processes such as the control of food intake and body weight, which are under the combined control of insulin and leptin.

Participation of prolactin receptors and phosphatidylinositol 3-kinase and MAP kinase pathways in the increase in pancreatic islet mass and sensitivity to glucose during pregnancy.

Prolactin (PRL) exerts its biological effects mainly by activating the Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling pathway. We have recently demonstrated that PRL also stimulates the insulin receptor substrates/phosphatidylinositol 3-kinase (IRSs/PI3K) and SH2-plekstrin homology domain (SHC)/ERK pathways in islets of neonatal rats. In the present study, we investigated the involvement of the PI3K and MAP kinase (MAPK) cascades in islet development and growth in pregnant rats. The protein expression of AKT1, p70S6K and SHC was higher in islets from pregnant compared with control rats. Higher basal levels of tyrosine phosphorylation were found in classic transducers of insulin cell signaling (IRS1, IRS2 and SHC). Increased levels of threonine/tyrosine phosphorylation of ERK1/2 and serine phosphorylation of AKT and p70S6K were also detected. To assess the participation of PRL in these phenomena, pregnant and control rats were treated with an antisense oligonucleotide to reduce the expression of the PRL receptor (PRLR). Phosphorylation of AKT was reduced in islets from pregnant and control rats, whereas p70S6K protein levels were reduced only in islets from treated pregnant rats. Finally, glucose-induced insulin secretion was reduced in islets from pregnant but not from control rats treated with the PRLR antisense oligonucleotide. In conclusion, downstream proteins of the PI3K (AKT and p70S6K) and MAPK (SHC and ERK1/2) cascades are regulated by PRL signaling in islets from pregnant rats. These findings indicate that these pathways participate in the increase in islet mass and the sensitivity to glucose during pregnancy.

Prolactin-modulated gene expression profiles in pancreatic islets from adult female rats.

The effects of prolactin (PRL) on transcript profile expression in 24h cultured pancreatic adult rat islets were investigated by cDNA expression array analysis to identify possible candidate mRNA species that encode proteins involved in the maturation and growth of the endocrine pancreas. The expression of 54 out of 588 genes was altered by treatment with PRL. The differentially expressed transcripts identified were distributed in six main categories involved in cell proliferation and differentiation, namely, cell cycle regulation, signal transduction, transcription factors and coactivators, translational machinery, Ca(2+)-mediated exocytosis, and immuno-response. Treatment with PRL also reduced the expression of genes related to apoptosis. Several genes, whose expression was previously not known to be modulated by PRL were also identified including macrophage migration inhibitory factor and Ca(2+)/calmodulin-dependent protein kinase IV. These genes have recently been shown to play a crucial role in insulin secretion and insulin gene expression, respectively. Treatment with PRL also modified the expression of AKT2 and bone morphogenetic protein receptor 1A that control glucose homeostasis and directly affect the behavior of endocrine pancreas and/or the sensitivity of target tissues to insulin. In conclusion, PRL induces several patterns of gene expression in pancreatic islet cells. The analysis of these different patterns will be useful for understanding the complex mechanism of action of PRL in the maturation and differentiation of pancreatic islets.