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Effects of curcumin and/or coenzyme Q10 supplementation on metabolic control in subjects with metabolic syndrome: a randomized clinical trial.
Sangouni, AA, Taghdir, M, Mirahmadi, J, Sepandi, M, Parastouei, K
Nutrition journal. 2022;21(1):62
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Metabolic syndrome (MetS) is a cluster of metabolic disorders such as hyperlipidaemia, hypertension, hyperglycaemia, insulin resistance, and abdominal obesity. MetS is associated with cardiovascular disease (CVD), type 2 diabetes mellitus and non-alcoholic fatty liver disease. The aim of this study was to investigate the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components in subjects with MetS. This study is a 2×2 factorial, randomised, double-blinded, placebo-controlled study which was conducted for 12 weeks. Eighty-eight subjects were randomly assigned into four groups. All subjects completed the trial. Results show that curcumin supplementation improves lipid profile, but it does not have any effect on body composition, hypertension and fasting plasma glucose. However, supplementation with coenzyme Q10 as well as curcumin plus coenzyme Q10 did not show any significant effects on lipid profile, body composition, hypertension and fasting plasma glucose. Authors conclude that curcumin supplementation (especially by its effects on dyslipidaemia) is more effective than coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 in the management of MetS. However, curcumin, coenzyme Q10 and their combination have no effect on body composition, hypertension and glycaemic control.
Abstract
BACKGROUND Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS. AIMS We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS. METHODS In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks. RESULTS The CP group compared with the three other groups showed a significant reduction in HDL-c (P = 0.001), TG (P < 0.001), TC (P < 0.001), and LDL-c (P < 0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight. CONCLUSION Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .
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Consumption of ultra-processed foods and health status: a systematic review and meta-analysis.
Pagliai, G, Dinu, M, Madarena, MP, Bonaccio, M, Iacoviello, L, Sofi, F
The British journal of nutrition. 2021;125(3):308-318
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Ultra-processed foods (UPF) are, according to the NOVA classification, “formulations of ingredients, mostly for industrial use only, derived from a series of industrial processes”. UPF represents an important and growing part of the world’s food supply. The aim of this study was to assess the relationship between UPF consumption as defined by NOVA and health status. This study is systematic review with meta-analysis of all the cross-sectional and cohort studies published to-date. At the end of the selection process, twenty-three articles were included in the qualitative analysis and nineteen in the quantitative analysis. Results indicate the possible association between high UPF consumption, worse cardiometabolic risk profile (reported by an increased risk of overweight/obesity, elevated waist circumference, reduced high-density lipoprotein-cholesterol levels and increased risk of the metabolic syndrome), and greater risk of all-cause mortality, cardiovascular disease, cerebrovascular disease and depression. Authors conclude that their findings have important public health implications, especially for food policymakers who should discourage the consumption of UPF and promote fresh and minimally processed foods to improve health status.
Abstract
Increasing evidence suggests that high consumption of ultra-processed foods (UPF) is associated with an increase in non-communicable diseases, overweight and obesity. The present study systematically reviewed all observational studies that investigated the association between UPF consumption and health status. A comprehensive search of MEDLINE, Embase, Scopus, Web of Science and Google Scholar was conducted, and reference lists of included articles were checked. Only cross-sectional and prospective cohort studies were included. At the end of the selection process, twenty-three studies (ten cross-sectional and thirteen prospective cohort studies) were included in the systematic review. As regards the cross-sectional studies, the highest UPF consumption was associated with a significant increase in the risk of overweight/obesity (+39 %), high waist circumference (+39 %), low HDL-cholesterol levels (+102 %) and the metabolic syndrome (+79 %), while no significant associations with hypertension, hyperglycaemia or hypertriacylglycerolaemia were observed. For prospective cohort studies evaluating a total population of 183 491 participants followed for a period ranging from 3·5 to 19 years, highest UPF consumption was found to be associated with increased risk of all-cause mortality in five studies (risk ratio (RR) 1·25, 95 % CI 1·14, 1·37; P < 0·00001), increased risk of CVD in three studies (RR 1·29, 95 % CI 1·12, 1·48; P = 0·0003), cerebrovascular disease in two studies (RR 1·34, 95 % CI 1·07, 1·68; P = 0·01) and depression in two studies (RR 1·20, 95 % CI 1·03, 1·40; P = 0·02). In conclusion, increased UPF consumption was associated, although in a limited number of studies, with a worse cardiometabolic risk profile and a higher risk of CVD, cerebrovascular disease, depression and all-cause mortality.
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Food processing and cardiometabolic risk factors: a systematic review.
Santos, FSD, Dias, MDS, Mintem, GC, Oliveira, IO, Gigante, DP
Revista de saude publica. 2020;54:70
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Cardiovascular diseases (CVD) comprise the main cause of mortality in the world and approximately three quarters of deaths occur in low- and middle-income countries. The aim of this study was to assess the association between food consumption according to processing and cardiometabolic factors in adults and/or the elderly. This study is a systematic review of eleven studies. Five studies (46%) had a sample size greater than 10,000 participants and the smallest sample identified evaluated 302 individuals. Results indicate that the consumption of UPF can have an unfavourable impact on the health of individuals, especially contributing to increase the body mass index. The cardiometabolic risk factors identified were overweight or obesity, arterial hypertension and metabolic syndrome. Authors conclude that their findings may contribute to strengthening scientific evidence that underlies public policies related to the area of food and nutrition and the coping with cardiovascular diseases.
Abstract
OBJECTIVE To systematically review the evidence for the association between food consumption according to processing and cardiometabolic factors in adults and/or the elderly. METHOD Two independent evaluators analyzed the electronic databases PubMed, Web of Science and Lilacs until December 2018. We used the following terms: (convenience foods OR food processing OR highly-processed OR industrialized foods OR minimally-processed OR prepared foods OR processed foods OR ultra-processed OR ultraprocessed OR ultra processed OR unprocessed) AND (metabolic syndrome OR hypertension OR blood pressure OR diabetes mellitus OR glucose OR glycaemia OR insulin OR cholesterol OR triglycerides OR blood lipids OR overweight OR obesity) AND (adult OR adults OR adulthood OR aged OR elderly OR old). We assessed methodological and evidence qualities, and also extracted information for the qualitative synthesis from the selected studies. RESULTS Of the 6,423 studies identified after removing duplicates, eleven met the eligibility criteria. The main food classification we used was Nova. The consumption of ultra-processed foods was positively associated with overweight and obesity, high blood pressure and metabolic syndrome. All articles included met more than 50% of the methodological quality criteria. The quality of evidence was considered moderate for the outcome overweight and obesity and weak for hypertension and metabolic syndrome. CONCLUSIONS The Nova food classification stands out in the area of nutritional epidemiology when assessing the effects of food processing on health outcomes. Although caution is required in the interpretation, the results indicated that the consumption of ultra-processed foods can have an unfavorable impact in the health of individuals.
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Visceral obesity, skeletal muscle mass and resistin in metabolic syndrome development.
Rodríguez-López, CP, González-Torres, MC, Cruz-Bautista, I, Nájera-Medina, O
Nutricion hospitalaria. 2019;36(1):43-50
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Obesity is a growing public health problem at a national and global level. Visceral adipose tissue (VAT) is the most bioactive component that is related with the release of inflammatory mediators which gives rise to insulin resistance, mainly local, and subsequently in liver and skeletal muscle. The aim of this study was to determine the relationship of body components with the concentration of resistin as an inflammatory marker in patients with overweight and obesity. The study is an observational, cross-sectional clinical study which analysed 40 participants with an age range between 18 and 40 years. Results indicate that: - as body mass index and VAT increased, anthropometric measurements, body composition, and biochemical indicators were altered. - persons with obesity and increased VAT had the highest proportions of metabolic syndrome (MS). - an increase in skeletal muscle is related with increased BMI and with the presence of increased VAT. - there was a significant increase in resistin concentration in individuals without MS and increased VAT compared to those without MS and normal VAT. Authors conclude that resistin might be acting as an inflammatory adipocytokine [a bioactive product produced by adipose tissue], contributing to the increase in frequency of MS in those persons who present increased levels of this cytokine.
Abstract
INTRODUCTION Background: obesity implies an increase in the visceral adipose tissue (VAT), which is a risk factor for various metabolic diseases. VAT releases proinflammatory mediators, like resistin. In addition, it has been noted that the skeletal muscle mass (SMM) is involved in the development of metabolic syndrome (MS). Objective: this study was designed to determine the relationship of body components (VAT and SMM) with MS and resistin in patients with obesity. Methods: body composition and anthropometric and biochemical measurements to assess MS, and ELISA tests for resistin were carried out in 40 patients aged 18-40 years. Results: overweight and obesity were observed in 72% of patients; visceral obesity was found in 53% and 35% had MS. A positive correlation between VAT and SMM in patients with MS was detected. In the entire population, an increase of 1 kg of SMM was found to be associated with an increase of 3 cm2 of VAT, and an increase of 4 cm2 of VAT was observed in individuals with MS. According to resistin, people with increased VAT had higher concentration than persons with normal VAT. Furthermore, an increase of 1 cm2 of VAT accounted for a person entertaining a 3.3 fold greater risk of MS for different values of SMM and resistin. Conclusion: the transcendence and significance of VAT as a main factor in triggering the chronic inflammatory process and MS, the SMM and resistin were also related. INTRODUCCIÓN: Introducción: la obesidad implica un aumento del tejido adiposo visceral (TAV), el cual es un factor de riesgo para varias enfermedades metabólicas. El VAT se relaciona con mediadores proinflamatorios, como la resistina. Además, se ha observado que la masa musculoesquelética (MME) interviene en el desarrollo del síndrome metabólico (SM). Objetivo: este estudio fue diseñado para determinar la relación de la composición corporal (TAV y MME) con el SM y la resistina en pacientes con obesidad. Métodos: se realizaron medidas antropométricas, de composición corporal y bioquímica para determinar el SM y prueba de ELISA para resistina en 40 pacientes de 18 a 40 años de edad. Resultados: se observó sobrepeso y obesidad en el 72% de los participantes, obesidad visceral en el 53% y el 35% presentó SM. Se detectó una correlación positiva entre el TAV y la MME en pacientes con SM. En el grupo de estudio encontramos que un aumento de un 1 kg de MME se asociaba con un incremento de 3 cm2 de TAV y en individuos con SM, con un incremento de 4 cm2 de TAV. En relación con la resistina, las personas con TAV incrementado presentan concentraciones más altas que las personas con TAV normal. Además, se observó que un aumento de 1 cm2 de TAV representa un riesgo 3,3 veces mayor que para las personas de padecer SM para diferentes valores de MME y de resistina. Conclusión: además de la trascendencia y la importancia del TAV como factor principal para desencadenar el proceso inflamatorio crónico y el SM, se observó que la MME y la resistina también están relacionadas.
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Assessment of the Effectiveness of a Computerised Decision-Support Tool for Health Professionals for the Prevention and Treatment of Childhood Obesity. Results from a Randomised Controlled Trial.
Moschonis, G, Michalopoulou, M, Tsoutsoulopoulou, K, Vlachopapadopoulou, E, Michalacos, S, Charmandari, E, Chrousos, GP, Manios, Y
Nutrients. 2019;11(3)
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Obesity is related to the increased risk for chronic diseases and to nutrient insufficiencies, a paradox that has been characterised as the “double burden of malnutrition”. The aim of this study was to examine the effectiveness of a computerised decision-support tool as a means of childhood obesity management. The effectiveness of the decision-support tool was assessed through a pilot randomised controlled intervention trial. The study recruited a total sample of 80 children (obese or overweight) with an age range between 6 and 12 years. The participants were allocated to two study groups – intervention group and control group. Results indicate that a computerised decision-support tool, designed to assist paediatric healthcare professionals in providing personalised nutrition and lifestyle optimisation recommendations to overweight or obese children and their parents, can result in favourable changes to certain dietary intake and anthropometric indices in the children that received the intervention. Authors conclude that the computerised decision-support tool resulted in improvement of the children’s dietary intake and body mass index. Hence, the tool can support clinicians to improve the effectiveness of care.
Abstract
We examined the effectiveness of a computerised decision-support tool (DST), designed for paediatric healthcare professionals, as a means to tackle childhood obesity. A randomised controlled trial was conducted with 65 families of 6⁻12-year old overweight or obese children. Paediatricians, paediatric endocrinologists and a dietitian in two children's hospitals implemented the intervention. The intervention group (IG) received personalised meal plans and lifestyle optimisation recommendations via the DST, while families in the control group (CG) received general recommendations. After three months of intervention, the IG had a significant change in dietary fibre and sucrose intake by 4.1 and -4.6 g/day, respectively. In addition, the IG significantly reduced consumption of sweets (i.e., chocolates and cakes) and salty snacks (i.e., potato chips) by -0.1 and -0.3 portions/day, respectively. Furthermore, the CG had a significant increase of body weight and waist circumference by 1.4 kg and 2.1 cm, respectively, while Body Mass Index (BMI) decreased only in the IG by -0.4 kg/m². However, the aforementioned findings did not differ significantly between study groups. In conclusion, these findings indicate the dynamics of the DST in supporting paediatric healthcare professionals to improve the effectiveness of care in modifying obesity-related behaviours. Further research is needed to confirm these findings.
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The Effect of Gluten Free Diet on Components of Metabolic Syndrome: A Randomized Clinical Trial
Ehteshami, M, Shakerhosseini, R, Sedaghat, F, Hedayati, M, Eini-Zinab, H, Hekmatdoost, A
Asian Pacific journal of cancer prevention : APJCP. 2018;19(10):2979-2984
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Metabolic syndrome is a cluster of conditions related to cardiovascular disorders risk factors such as blood pressure, dyslipidaemia, hyperglycaemia, excess body fat around the waist and insulin resistance. The aim of this study was to assess the effects of a gluten-free diet on components of metabolic syndrome in patients diagnosed with metabolic syndrome. The study is a randomised control trial that recruited fifty subjects diagnosed with metabolic syndrome. Subjects were block randomised by gender into control and gluten-free diet groups. Results showed that a gluten-free diet induces significant reduction in waist circumference in comparison to control diet. Reduction in waist circumference without significant reduction in body weight may indicate preferential loss of abdominal fat. Furthermore, results indicate that a gluten-free diet improved glucose tolerance. Authors conclude that a gluten-free diet significantly improved some key features of metabolic syndrome including blood glucose and serum triglycerides.
Abstract
Background: This study aimed to assess the effects of Gluten free diet (GFD) on components of metabolic syndrome (MES). Materials and Methods: In this randomized clinical trial, 50 subjects diagnosed with MES were randomly divided into two groups (n=25). The first group received a GFD and the second group continued their regular diet. Biochemical markers of MES and blood pressure were measured before and after 8-week intervention. Results: Forty five subjects completed the study. A post-hoc comparison of the groups showed no effects of the GFD and control diet on LDL cholesterol, total cholesterol, fasting insulin, HOMA-IR, systolic and diastolic blood pressure levels. The GFD reduced fasting blood glucose, waist circumference (WC) and serum triglyceride concentration significantly compared with the control diet (p<0.05). Conclusion: Short-term GFD reduced WC and improved glycemic control and Triglyceride level in subjects with the metabolic syndrome.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Effectiveness and safety of carbohydrate counting in the management of adult patients with type 1 diabetes mellitus: a systematic review and meta-analysis.
Vaz, EC, Porfírio, GJM, Nunes, HRC, Nunes-Nogueira, VDS
Archives of endocrinology and metabolism. 2018;62(3):337-345
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Glycaemic control of patients with diabetes mellitus is important because it impacts the development of diabetic complications. Carbohydrate counting is a meal planning tool that allows for great variation and flexibility in food choices among individuals with diabetes mellitus. The aim of the study was to evaluate the effectiveness and safety of carbohydrate counting in the treatment of adult patients with type 1 diabetes mellitus using a systematic literature review. The study included randomised controlled trials with at least 3 months of follow-up, and evaluation of outcomes in which patients were randomly divided into two groups. The meta-analysis showed that the final haemoglobin A1c (HbA1c) - a test that shows the average blood glucose levels for the last two to three months - was significantly lower in the carbohydrate counting group than in the control group. Authors conclude that the meta-analysis showed evidence favouring the use of carbohydrate counting in the management of adult patients with type 1 diabetes mellitus. However, this benefit was limited to the final HbA1c.
Abstract
OBJECTIVE This study aimed to evaluate the effectiveness and safety of carbohydrate counting (CHOC) in the treatment of adult patients with type 1 diabetes mellitus (DM1). MATERIALS AND METHODS We performed a systematic review of randomized studies that compared CHOC with general dietary advice in adult patients with DM1. The primary outcomes were changes in glycated hemoglobin (HbA1c), quality of life, and episodes of severe hypoglycemia. We searched the following electronic databases: Embase, PubMed, Lilacs, and the Cochrane Central Register of Controlled Trials. The quality of evidence was analyzed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS A total of 3,190 articles were identified, and two reviewers independently screened the titles and abstracts. From the 15 potentially eligible studies, five were included, and 10 were excluded because of the lack of randomization or different control/intervention groups. Meta-analysis showed that the final HbA1c was significantly lower in the CHOC group than in the control group (mean difference, random, 95% CI: -0.49 (-0.85, -0.13), p = 0.006). The meta-analysis of severe hypoglycemia and quality of life did not show any significant differences between the groups. According to the GRADE, the quality of evidence for severe hypoglycemia, quality of life, and change in HbA1c was low, very low, and moderate, respectively. CONCLUSION The meta-analysis showed evidence favoring the use of CHOC in the management of DM1. However, this benefit was limited to final HbA1c, which was significantly lower in the CHOC than in the control group.
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Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor.
Gonzalez, E, Flier, E, Molle, D, Accili, D, McGraw, TE
Proceedings of the National Academy of Sciences of the United States of America. 2011;108(25):10162-7
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Insulin resistance develops following extended periods of high insulin production, making cells unresponsive to its actions, however not all insulin functions are equally affected. Patients with Type 2 diabetes have impaired insulin regulation of glucose with increased fat storage in the liver. This results in a combination of raised insulin, glucose and triglycerides in the blood (hyperinsulinemia, hyperglycaemia, and hypertriglyceridemia), which affect health outcomes. Studies have shown that 'selective insulin resistance' occurs in the liver, however the molecular mechanisms by which this occurs are not known. It is also not known whether this is liver-specific or occurs in other insulin responsive tissues in the body. This in-vitro (cell culture) study found that high levels of insulin disturbs the PI3-kinase/Akt signalling pathway resulting in selective insulin resistance in fat cells (adipocytes), whilst expression of FoxO1 transcription factor (which controls lipid metabolism) is maintained. These changes are the result of inherent differences in insulin sensitivity of GLUT4 translocation and FoxO1 nuclear exclusion. The authors conclude that in a model of chronic hyperinsulinemia, fat cells develop a state of selective insulin resistance. Uncoupled insulin action, a phenomenon first described in the insulin-resistant liver, might be a general feature of insulin-resistant tissues consequent to deregulation of PI3-kinase/Akt signalling.
Abstract
Insulin resistance is a component of the metabolic syndrome and Type 2 diabetes. It has been recently shown that in liver insulin resistance is not complete. This so-called selective insulin resistance is characterized by defective insulin inhibition of hepatic glucose output while insulin-induced lipogenesis is maintained. How this occurs and whether uncoupled insulin action develops in other tissues is unknown. Here we show in a model of chronic hyperinsulinemia that adipocytes develop selective insulin resistance in which translocation of the GLUT4 glucose transporter to the cell surface is blunted yet nuclear exclusion of the FoxO1 transcription factor is preserved, rendering uncoupled insulin-controlled carbohydrate and lipid metabolisms. We found that in adipocytes FoxO1 nuclear exclusion has a lower half-maximal insulin dose than GLUT4 translocation, and it is because of this inherent greater sensitivity that control of FoxO1 by physiological insulin concentrations is maintained in adipocytes with compromised insulin signaling. Pharmacological and genetic interventions revealed that insulin regulates GLUT4 and FoxO1 through the PI3-kinase isoform p110α, although FoxO1 showed higher sensitivity to p110α activity than GLUT4. Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1. We propose that the lower threshold of insulin activity for FoxO1's nuclear exclusion is in part due to its regulation by both Akt isoforms. Identification of uncoupled insulin action in adipocytes suggests this condition might be a general phenomenon of insulin target tissues contributing to insulin resistance's pathophysiology.