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Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle.

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Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks. Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry. Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced. Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

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The purposes of the present study were to analyze liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) for 6 months or a SRD for 3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time developed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. Hepatic NAS, IL-1ß, NFκB p65, PAI-1, and F4-80 expression, as well as MPO activity were significantly increased and IL-10 expression was significantly decreased; this was accompanied by increased plasma IL-6 and TNF-α levels in rats fed a SRD. In addition, serum and liver nitric oxide (NO) levels and nitric oxide synthase (NOS) were significantly increased in the SRD group. In addition, a significant increase in hepatic iNOS expression and a positive correlation of this with liver NFκB p65 was found. We observed a significant increase in hepatic intercellular adhesion molecule (ICAM), and a negative correlation of this with liver Nrf2 was found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. In the liver tissue, NAS, IL-1ß, IL-10, NFκB p65, PAI-1, and F4-80 expression and MPO activity were normalized. Serum and liver NO and NOS levels and hepatic iNOS expression were decreased and this last one was associated with a decrease in liver NFκB p65 levels. Hepatic ICAM-1 was normalized and negatively correlated with liver NrF2 levels. This study showed new aspects of liver inflammation and endothelial dysfunction in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. In addition, we demonstrated new properties and molecular mechanisms associated with beneficial effects on inflammation and endothelial dysfunction of chia seed as a therapeutic strategy.

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The effects of microcapsules containing brewer's spent grain (BSG) peptides were evaluated on a hypertensive/insulin-resistant rat model induced by a sucrose-rich diet (SRD) administration. Animals received for 100 days the control diet (CD), SRD, and CD and SRD diets supplemented with microencapsulated peptides (CD-P and SRD-P). During the experimental period, blood pressure was monitored. Glycemia, tissue glycogen content, nitric oxide, and the activity of enzymes related to hypertensive and diabetogenic mechanisms were determined. The consumption of SRD caused hypertensive and hyperglycemic effects compared to CD. However, the SRD-P group presented lower systolic pressure at the middle of ingestion, achieving similar values than the CD. The SRD-P rats decreased all enzymes' activities compared to the SRD reaching the values of CD, except for those of α-amylase in cecal content and DPP-IV in serum. It was possible to corroborate potential antihypertensive and antidiabetogenic in vivo effects of the microencapsulated BSG peptides. PRACTICAL APPLICATIONS: Brewer's spent grain (BSG) is the main waste obtained from brewing industry. Bioactive peptides obtained after an enzymatic hydrolysis of proteins with in vitro antihypertensive and antidiabetogenic activity have been described. However, to corroborate the action of these bioactive peptides, in vivo studies are necessary. In the present work, microcapsules containing bioactive peptides from BSG were administered on the rat model with induced hypertension and insulin-resistance, corroborating an in vivo antihypertensive and antidiabetogenic effects by inhibition of enzymes related with blood pressure regulation and glucose metabolism. This work demonstrated that microcapsules of BSG peptides could be included into functional foods formulations, or used as dietary supplement for improving health and the prevention of non-communicable diseases, adding value to the brewing process by-product.

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The aim of this study was to analyze the liver injury and oxidative stress in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) -6 months- or a SRD -3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD+CHIA). The results showed that rats fed with a SRD for a long period of time developed dyslipidemia, hyperglycemia, hepatic lipid accumulation, liver injury, hepatic lipid peroxidation and oxidative stress. Hepatic NrF2 expression was significantly decreased. In addition, a significant increase in hepatic NFκB p65 expression and a positive correlation of this with plasma TNFα levels were found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, lipid accumulation, liver injury, lipid peroxidation and oxidative stress. In the liver tissue, NrF2 expression was normalized and NFκB p65 expression was decreased, the latter was associated with a decrease in plasma TNFα levels. The present study showed new aspects of liver damage, lipid peroxidation and oxidative stress in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. However, we demonstrated new properties and molecular mechanisms associated with the beneficial anti-oxidant effects of chia seed consumption.

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The aim of this study was to analyze blood coagulation, endothelial dysfunction and liver fibrosis in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) - 6 months - or a SRD - 3 months. Then, the last group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as the source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time develop dyslipidemia, visceral adiposity, insulin resistance, and a hypercoagulable and hypofibrinolytic basal state. Hepatic VCAM-1 (main adhesion molecules involved in endothelial dysfunction) expression was significantly increased. In addition, the SRD group presented hepatic steatosis, a significant increase in interstitial collagen deposition and hydroxyproline content. Liver TGF-ß1 (a key cytokine involved in fibrogenesis) levels increased and a negative correlation with PPARα protein mass levels was found. The administration of chia seed for 3 months reversed dyslipidemia, visceral adiposity and insulin resistance. Platelet count, coagulation parameters and plasma fibrinogen levels were normalized. In the liver tissue, VCAM-1 expression, steatosis, interstitial collagen deposition and the hydroxyproline content decreased. TGF-ß1 expression was decreased and this was associated with an increase in the PPARα protein levels. The present study showed new aspects in the progression from liver steatosis to fibrosis in dyslipidemic insulin-resistant rats chronically fed a sucrose-rich diet. Chia seed supplementation could be used as a functional food and a potential dietary strategy to prevent or ameliorate disorders related to atherothrombotic cardiovascular events and NASH.

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The aim of this study was to analyze the effects of Salvia hispanica L. (chia) seed upon metabolic pathways that play a key role in adipose tissue lipid handling which could be involved in visceral adiposity reduction developed in rats fed a sucrose-rich diet (SRD). Male Wistar rats were fed with a reference diet (RD) -6 months- or SRD-3 months. Then, the last group was randomly divided into two subgroups. One subgroup continued receiving the SRD up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as the source of dietary fat for the next 3 months (SRD + CHIA). Results showed that chia seed in the SRD-fed rat reduced the abdominal and thoracic circumferences, carcass fat content, adipose tissue weights, and visceral adiposity index. This was accompanied by an improvement in insulin sensitivity and plasma lipid profile. In epididymal adipose tissue, the decreased fat cell triglyceride content was associated with a reduction in both, FAT/CD 36 plasma membrane levels and the fat synthesis enzyme activities. There were not changes in oxidative CPT enzyme activities. PKCß and the precursor and mature forms of SREBP-1 protein levels were decreased, while pAMPK was increased. Our findings suggest that chia seed supplementation can modulate essential pathways of lipid metabolism in adipose tissue, contributing to reduced visceral fat accumulation in SRD-fed rats.

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Introducción: el acúmulo de lípidos en el músculo esquelético se encuentra estrechamente vinculado con el desarrollo de la resistencia insulínica. Esta última cumple un rol patogénico central en el desarrollo de numerosos desórdenes metabólicos incluidos en el síndrome metabólico. Objetivos: analizar algunas vías metabólicas implicadas en el acúmulo de lípidos en el músculo esquelético y su asociación con la resistencia insulínica en un modelo experimental que mimetiza el fenotipo del síndrome metabólico humano. Materiales y métodos: ratas macho Wistar recibieron una dieta control (DC) o una dieta rica en sacarosa (DRS) durante seis meses. Al final del período experimental se analizó en músculo esquelético gastrocnemio: contenido de triglicéridos (TG), acil-CoA de cadena larga y diacilglicerol, actividad enzimática carnitina palmitoil transferasa muscular (M-CPT1, M-CPT2 y M-CPT total) y masa proteica del PPARα, AMPK y AMPKp. Se determinaron los niveles séricos de TG, AGNE, glucosa, insulina, TNFα y adiponectina. La sensibilidad insulínica se midió por la técnica clamp euglucémica-hiperinsulinémica. Resultados: en los animales alimentados con DRS la dislipemia, hiperglucemia moderada, insensibilidad insulínica e incremento del contenido de especies lipídicas en el músculo esquelético se acompañaron de una disminución en la actividad enzimática M-CPT1 y M-CPT total, y un descenso de la masa proteica del PPARα. Además se observó una reducción de la masa proteica de la AMPKp, la cual se correlacionó con bajos niveles de adiponectina y elevados niveles de TNFα séricos. Conclusiones: los resultados aportan nuevos datos sobre algunos mecanismos involucrados en el desarrollo de la lipotoxicidad en el músculo esquelético en ratas dislipémicas insulinorresistentes

Introduction: the skeletal muscle lipid accumulation is closely linked to the development of insulin resistance. The latter plays a central pathogenic role in the development of numerous metabolic disorders included in the metabolic syndrome. Objectives: to analyze some metabolic pathways involved in the skeletal muscle lipid accumulation and its association with insulin resistance in an experimental model that mimics the phenotype of the human metabolic syndrome. Materials and methods: male Wistar rats received a control diet (CD) or a sucrose rich diet (SRD) for six months. At the end of the experimental period, in gastrocnemius skeletal muscle were analyzed: triglyceride (TG), long chain acyl-CoA and diacylglycerol (DAG) contents, muscle carnitine palmitoyl transferase enzymes activities (M-CPT1, M-CPT2 and total M-CPT) and protein mass levels of PPARα, AMPK and AMPKp. Serum levels of TG, AGNE, glucose and insulin, TNFα and adiponectin were determined. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp technique. Results: in SRD fed animals, dyslipidemia, moderate hyperglycemia, insulin insensitivity and the increased content of lipid species in the skeletal muscle were accompanied by a decrease in the enzymes activities of both M-CPT1 and total M-CPT and protein mass levels of PPARα. In addition, a reduction in the protein mass levels of AMPKp was observed, which was correlated with low serum levels of adiponectin and high levels of TNFα. Conclusions: the results provide new data on some mechanisms involved in the development of lipotoxicity in skeletal muscle in insulin resistant dyslipidemic rats

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Introducción: la enfermedad celíaca (EC) es un trastorno sistémico, mediado inmunológicamente y desencadenado por la ingestión de gluten en individuos genéticamente susceptibles. El único tratamiento es una dieta libre de gluten estricta y de por vida, que requiere cambiar un hábito tan cotidiano y consolidado como la alimentación. Objetivos: conocer los servicios gastronómicos comerciales del distrito centro de la ciudad de Santa Fe que brindan alimentos libres de gluten, la variedad de preparaciones aptas y el conocimiento de los manipuladores sobre la enfermedad y la manipulación segura de estos alimentos. Materiales y métodos: estudio descriptivo, observacional y transversal, aplicado a una muestra de 80 servicios gastronómicos. Se realizaron dos encuestas (una al manipulador de alimentos y otra al encargado del establecimiento) y una observación directa de la lista de menús. Resultados: el 90% de los manipuladores informó conocer qué es la EC. El 10% (n=8) de los establecimientos contaba con al menos un menú libre de gluten, y de éstos, sólo el 12,5% (1) cumplía con todas las pautas para la elaboración de alimentos libres de gluten. El 50% (4) contaba con cinco o más platos sin gluten, limitándose la variedad a farináceos, carnes con guarnición y ensaladas. Conclusiones: los manipuladores de alimentos conocen algunos aspectos de la EC, sin embargo, son escasos los establecimientos que brindan preparaciones seguras libres de gluten. Es necesario dar mayores oportunidades sociales a las personas con EC a fin de reducir el riesgo de transgresiones alimentarias.

Introduction: celiac disease (CD) is a systemic disorder, mediated immunologically and triggered by the ingestion of gluten in genetically susceptible individuals. The only treatment is a strict gluten-free diet for life, which requires changed a habit as daily and consolidated as food. Objectives: to know the commercial gastronomic services of the downtown district of the city of Santa Fe that offer gluten-free foods, the variety of suitable preparations and the knowledge of the manipulators about the disease and the safe handling of these foods. Materials and methods: descriptive, observational and transversal study, applied to a sample of 80 gastronomic services. Two surveys were carried out (one to the food handler and another to the establishment manager) and a direct observation of the menu list. Results: the 90% of the food handlers were informed about the disease. 10% of the facilities (n=8) had at least one glutenfree menu, of which just only a 12.5% (1) fulfilled all the requirements for the processing of gluten-free foodstuffs. Only a 50% (4) had five or more gluten-free dishes which were mainly prepared with starchy products, garnished meat and vegetables. Conclusions: while many food handlers know certain aspects of CD, only a few food facilities provide safe glutenfree preparations. It is necessary to promote greater social opportunities to those suffering from CD in order to reduce the risk of dietary infringements.

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The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the time course of the development of oxidative stress, changes in proinflammatory cytokines and adiponectin levels, and their relationship with insulin resistance. We analyzed the morphometric characteristics of epididymal adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant defense, inflammatory mediators, adiponectin levels and insulin resistance in rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a control diet. The results showed a depletion of antioxidant enzyme activities in the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet. Superoxide dismutase activity and the redox state of glutathione showed a significant decrease at weeks 15 and 30. This was accompanied by visceral adiposity and enhanced lipogenic enzyme activities. An increase in the plasma levels of proinflammatory markers (TNF-α and IL-6) was recorded only after 30 weeks on the diet. A reduction in plasma adiponectin levels accompanied the time course of deterioration of whole-body insulin sensitivity. The results suggest that lipid peroxidation, depletion of antioxidant defenses and changes in inflammatory cytokines induced by a sucrose-rich diet contribute to the dysregulation of adipose tissue and insulin resistance. Finally, these results show that the progressive deterioration of adipose tissue function, which begins in the absence of both visceral adiposity and overweight, is highly dependent on the length of time on the diet.

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Nutritional insults during pregnancy and lactation (P + L) are often associated with offspring health risks. We investigated the effect of maternal exposure to a sucrose-rich diet (SRD) during P + L on glucose and lipid metabolism of adult offspring regardless of post-weaning diet. Dams were fed an SRD or a control diet (CD) during P + L. After weaning, male offspring from SRD and CD dams were divided into two groups and fed a CD or SRD until 150 days old forming CD-CD, CD-SRD, SRD-SRD and SRD-CD groups. Offspring where SRD was fed at any period of life showed: (1) increased adipose tissue weight without changes in the final body weight; (2) dyslipidemia as a result of increased very low density lipoprotein triglyceride secretion rate and decreased triglyceride clearance; (3) hepatic steatosis associated with increased activity of key enzymes involved in liver de novo lipogenesis and significant decrease of the activity of mitochondrial fatty acid oxidation enzyme. These results were more pronounced in CD-SRD and SRD-SRD groups. (4) Hyperglycemia without changes in insulin levels, plus a deterioration of intravenous glucose tolerance and intraperitoneal insulin tolerance test. We hypothesized that SRD during P + L could be associated with a programming effect on glucose homeostasis and hepatic lipid metabolism that predispose offspring to develop later-life insulin resistance and metabolic disorders, regardless of post-natal diet.

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The present study analyzes several markers of energy metabolism in the heart muscle of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD, 62.5% wt/wt) for 8 months. It also explores the possible beneficial effects of dietary fish oil supplementation on cardiac lipids and glucose metabolism. With this purpose, male Wistar rats were fed an SRD for 6 months. Whereas half of the animals continued with the same diet for up to 8 months, the other half was fed an SRD in which fish oil (7% + 1% corn oil wt/wt) replaced corn oil (8% wt/wt) from months 6 to 8. The results were compared with rats fed a control diet (starch 62.5% wt/wt). The cardiac muscle of SRD-fed rats showed (1) a significant reduction (P < .05) in key enzymes activities and metabolites involved in glucose metabolism, accompanied by a significant (P < .05) increase of lipid storage (triglyceride, long-chain acyl coenzyme A, and diacylglycerol), and (2) a significant increase (P < .05) of nPKCepsilon protein mass expression in the membrane fraction without changes in the cPKCbetaII. Dietary fish oil, which reduces the availability of plasma lipid flux and normalizes glucose homeostasis, was able to reverse heart muscle lipotoxicity. Fish oil benefits key enzymes activities in glucose metabolism and normalizes glycogen and glucose-6-phosphate concentration, and the altered nPKCepsilon protein mass expression translocation in the heart of SRD-fed rats. Our findings suggest that manipulation of dietary fats may play a key role in the management of lipid disorders, offering a protection against the development of cardiovascular diseases.

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Feeding rats a sucrose rich diet (SRD) induces hypertriglyceridemia and insulin resistance. The purposes of this study were to determine the time course of changes in lipid and glucose metabolism in the gastrocnemius muscle, both in the basal state and after the euglycemic hyperinsulinemic clamp, in rats fed a SRD for 3, 15 or 30 wk, and to analyze the changes in glucose-stimulated insulin secretion from perifused isolated islets from SRD-fed rats and their relationships to peripheral insulin insensitivity. A control group of rats was fed a control diet (CD) for the same period of time. After 3 wk of consuming the SRD, long-chain acyl CoA (LCACoA) levels in muscle were greater than in rats fed the CD, an early indication of the disturbance of lipid metabolism. Neither glycogen storage nor glucose oxidation were impaired at this time. Moreover, the biphasic patterns of glucose-stimulated insulin secretion showed a marked increase in the first peak, which helped maintain normoglycemia in SRD-fed rats. After 15 or 30 wk of consuming the SRD, triglyceride and LCACoA levels in muscles were greater than in rats fed the CD. Glucose oxidation as well as insulin-stimulated glycogen synthase activity and glycogen storage were lower than in rats fed the CD. Moreover, the altered pattern of insulin secretion further deteriorated. This was accompanied by peripheral insulin resistance and moderate hyperglycemia. Our results indicate that the dyslipemia present in rats chronically fed a SRD may play an important role in the progressive deterioration of insulin secretion and sensitivity in this animal model.

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