Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion

β-Cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism (14CO2 and 3H2O production from D-[U-14C]- and D-[5-3H]-glucose) and HK/GK activity (G-6-P production), transcription (RTPCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, β-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon β-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked β-cell mass reduction.Centro de Endocrinología Experimental y Aplicad

Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion

β-Cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism (14CO2 and 3H2O production from D-[U-14C]- and D-[5-3H]-glucose) and HK/GK activity (G-6-P production), transcription (RTPCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, β-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon β-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked β-cell mass reduction.Centro de Endocrinología Experimental y Aplicad

Ontogénesis y evolución de la masa de células INGAP (Islet Neogenesis Associated Protein) positivas en el período intrauterino y en adultos con insulinorresistencia fisiológica (ratas preñadas)

Objetivos: Estudiar la cronología de aparición de células INGAP positivas en fetos de ratas normales y la evolución simultánea de su masa y la de las células β en ratas preñadas y su presencia en el páncreas de rata.Facultad de Ciencias Médica

Rol de la actvidad del NADPH oxidasa insular sobre los cambios en la secreción de insulina inducidos por una dieta rica en fructuosa

La dieta rica en fructosa (DRF) induce estrés oxidativo (EO), insulinorresistencia, tolerancia a la glucosa alterada y disminución de la masa de células β. Previamente ha sido demostrada la presencia de NADPHoxidasa (NOXi) a nivel insular; por otro lado, su actividad varía en función de diferentes estímulos de la secreción de insulina. Hasta el momento se desconoce el rol de la NOXi sobre los cambios inducidos por DRF en la función insular.Facultad de Ciencias Médica

A comprehensive analysis of the genetic diversity and environmental adaptability in worldwide Merino and Merino-derived sheep breeds

BACKGROUND: To enhance and extend the knowledge about the global historical and phylogenetic relationships between Merino and Merino-derived breeds, 19 populations were genotyped with the OvineSNP50 BeadChip specifically for this study, while an additional 23 populations from the publicly available genotypes were retrieved. Three complementary statistical tests, Rsb (extended haplotype homozygosity between-populations), XP-EHH (cross-population extended haplotype homozygosity), and runs of homozygosity (ROH) islands were applied to identify genomic variants with potential impact on the adaptability of Merino genetic type in two contrasting climate zones. RESULTS: The results indicate that a large part of the Merino's genetic relatedness and admixture patterns are explained by their genetic background and/or geographic origin, followed by local admixture. Multi-dimensional scaling, Neighbor-Net, Admixture, and TREEMIX analyses consistently provided evidence of the role of Australian, Rambouillet and German strains in the extensive gene introgression into the other Merino and Merino-derived breeds. The close relationship between Iberian Merinos and other South-western European breeds is consistent with the Iberian origin of the Merino genetic type, with traces from previous contributions of other Mediterranean stocks. Using Rsb and XP-EHH approaches, signatures of selection were detected spanning four genomic regions located on Ovis aries chromosomes (OAR) 1, 6 and 16, whereas two genomic regions on OAR6, that partially overlapped with the previous ones, were highlighted by ROH islands. Overall, the three approaches identified 106 candidate genes putatively under selection. Among them, genes related to immune response were identified via the gene interaction network. In addition, several candidate genes were found, such as LEKR1, LCORL, GHR, RBPJ, BMPR1B, PPARGC1A, and PRKAA1, related to morphological, growth and reproductive traits, adaptive thermogenesis, and hypoxia responses. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive dataset that includes most of the Merino and Merino-derived sheep breeds raised in different regions of the world. The results provide an in-depth picture of the genetic makeup of the current Merino and Merino-derived breeds, highlighting the possible selection pressures associated with the combined effect of anthropic and environmental factors. The study underlines the importance of Merino genetic types as invaluable resources of possible adaptive diversity in the context of the occurring climate changes

Posible efecto de los canabinoides endógenos y el rimonabant sobre la insulinorresistencia y la función de las células β

El propósito del trabajo es estudiar el posible papel regulador del sistema canabinoide sobre la secreción de insulina y los cambios endocrino-metabólicos inducidos en ratas normales por una dieta rica en fructosa (DRF).Facultad de Ciencias Médicas (FCM

A Fuzzy Linguistic Summarization Technique for TV Recommender Systems

is resulting in a soaring number of broadcast programs available to viewers. To alleviate this problem, Personal Video Recorders (multimedia platforms which record TV programs on a hard disk) should integrate a recommender system, which purpose is to filter programs according to their relevance. These systems are based on a user profile, acting as a representative for the user's interests. An important research issue resides in going beyond explicitly userdefined profiles

Effect of gradation on volumetric and mechanical properties of cold recycled mixtures (CRM)

In recent times, recycling using cold bituminous mixtures has become one of the most interesting techniques in pavement engineering from sustainability aspect. This study focuses on the clarification of the steps concerned with the cold mixture mix design to determine the initial aggregate gradation of the mixture. The study has been developed involving procedures followed in Canada and Italy. In both the cases, three different gradations, normally employed in the production of traditional bituminous mixtures, were compared. The effect conferred by the gradation type has been studied in terms of workability, compactability and mechanical properties. Results show that in both the procedures the gradation influenced the workability and the compaction behaviour of the mixtures studied. At the same time, in terms of mechanical properties, the gradation influenced the strength of the final mixture in only one of the procedures applied

Influence of Curing on the Mechanical Properties of Cement-Bitumen Treated Materials Using Foamed Bitumen: An Interlaboratory Test Program

The use of reclaimed asphalt (RA) in road pavements is continuously gaining interest thanks to the technical, economic and environmental advantages guaranteed by such sustainable practice. Cold recycling techniques compared to traditional asphalt mixes allow a significant reduction of energy, fume emissions, use of natural resources, etc. In this perspective, the Task Group 1 on \u201cCold Recycling\u201d of the RILEM Technical Committee on \u201cAsphalt Pavement Recycling\u201d (TC 264-RAP) launched an interlaboratory test program (ITP) aimed at ensuring a better understanding for cold recycled mixtures. The paper presents the results collected by a restricted group of the participating laboratories testing cement-bitumen treated materials that included a single RA source and prepared with foamed bitumen. Gyratory compacted specimens were used to evaluate the influence of curing (free, partial or restricted-surface drying for 14\ua0days at 40\ua0\ub0C at a relative humidity of 55 \ub1 5%). Stiffness was evaluated as a function of the curing stage and the corresponding water loss; strength was tested after 14\ua0days of curing testing specimens in both dry and wet conditions to also determine the water sensitivity. As expected, the different curing conditions clearly influenced the rate of water loss of tested samples with clear effects on mechanical properties and durability