scholarly journals Voluntary exercise under a food restriction condition decreases blood branched-chain amino acid levels, in addition to improvement of glucose and lipid metabolism, in db mice, animal model of type 2 diabetes

2014 ◽  
Vol 19 (5) ◽  
pp. 339-347 ◽  
Author(s):  
Ancah Caesarina Novi Marchianti ◽  
Emi Arimura ◽  
Miharu Ushikai ◽  
Masahisa Horiuchi

2016 ◽  
Vol 14 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Sjaam Jainandunsing ◽  
J.L. Darcos Wattimena ◽  
Adrie J.M. Verhoeven ◽  
Janneke G. Langendonk ◽  
Trinet Rietveld ◽  
...  


Diabetologia ◽  
2021 ◽  
Author(s):  
Rasmus J. O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  

Abstract Aims/hypothesis Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. Methods Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation. Results Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretation Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent. Graphical abstract



2011 ◽  
Vol 23 (4) ◽  
pp. 217-225
Author(s):  
Yukiyo KANEKO ◽  
Koji KUBOKI ◽  
Naoki HIROI ◽  
Takehiko WATANABE ◽  
Chiaki NISHIMURA ◽  
...  


2020 ◽  
Author(s):  
Rasmus J.O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  

SUMMARYIncreased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes (T2D) pathogenesis. However, most metabolomic studies in T2D are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a glucose challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism in T2D is partially unknown. Using metabolomic and gene expression approaches, we found that impairments in BCAA catabolism in T2D patients under fasting conditions are exacerbated after a glucose load, concomitant with downregulated expression of BCAA-related genes in skeletal muscle. We identified a key regulatory role for Estrogen-Related Receptor α (ERRα) in PGC-1α-mediated upregulation of BCAA genes and leucine oxidation. Thus, metabolic inflexibility in T2D impacts BCAA homeostasis and the transcriptional regulation of BCAA genes via a PGC-1α/ERRα-dependent mechanism.



2012 ◽  
Vol 167 (4) ◽  
pp. 569-578 ◽  
Author(s):  
Francisco J Ortega ◽  
Mónica Sabater ◽  
José M Moreno-Navarrete ◽  
Neus Pueyo ◽  
Patricia Botas ◽  
...  

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.



2018 ◽  
Vol 64 (2) ◽  
pp. 39-45 ◽  
Author(s):  
Nataliia Gorbenko ◽  
Oleksii Borikov ◽  
Olha Ivanova ◽  
K. V. Taran ◽  
T. S. Litvinova ◽  
...  

A sex difference of carbohydrate and lipid metabolism disorders in rats with type 2 diabetes has been studied. It was established that type 2 diabetes leads to a more pronounced deterioration in carbohydrate toleranceand insulin sensitivity in males compared to female rats, but the sex doesn’t affect basal glycemia and fructosamine levels. It was found that the increase of body weight and visceral fat in rats with type 2 diabetes is moremanifested in females than in males. It has been determined that hypertriglyceridemia is higher in diabeticmales compared to diabetic females, and the level of common lipids in the liver, both intact females and femaleswith type 2 diabetes, is lower than that of the males. The obtained results indicate a more expressive impairment of glucose and lipid metabolism in males compared to females with type 2 diabetes



2017 ◽  
Vol 9 (5) ◽  
pp. 403-409 ◽  
Author(s):  
Hirokazu Kakuda ◽  
Junji Kobayashi ◽  
Masaru Sakurai ◽  
Masahiro Kakuda ◽  
Noboru Takekoshi


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