Integration of the metabolic and cardiovascular effects of exercise

2006 ◽  
Vol 42 ◽  
pp. 193-210 ◽  
Author(s):  
Anton J.M. Wagenmakers ◽  
Natal A.W. van Riel ◽  
Michael P. Frenneaux ◽  
Paul M. Stewart
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Cardiovascular Effects ◽  
Vascular Wall ◽  
Nuclear Factor Κb ◽  
Calorie Intake ◽  
Signal Molecules ◽  
Muscle Fibres ◽  
Irreversible Damage

Most of the essays in this volume have adopted a reductionist approach and have focused on the biochemistry either in skeletal muscle or in the vascular wall. There is however a complex interaction between the biochemistry in the endothelium of the microvascular wall, the vascular smooth muscle and the skeletal muscle fibres involving signalling pathways in the three tissues and an intense exchange of signal molecules between them. In the present essay an integrative overview is given of this complex metabolic interaction and the impairments in it that lead to type 2 diabetes and cardiovascular disease.A reduced nitric oxide production by the (micro)vascular endothelium is identified as the key event and is reversible by regular exercise and a reduced calorie intake. The chapter also contains a description of the complex metabolic network controlled by the inducible transcription factor nuclear factor-κB, that is activated in more advanced stages of the chronic diseases, and either leads to repair of the microvascular wall or to irreversible damage and the severe complications of end stage cardiovascular disease and type 2 diabetes.

scholarly journals Nitric oxide synthase in skeletal muscle fibres of patients with type 2 diabetes

2012 ◽  
Author(s):  
Karla Punkt ◽  
Katharina Kandt ◽  
Andreas Oberbach ◽  
Volker Adams ◽  
Igor Buchwalow ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Muscle Fibres ◽  
Oxide Synthase ◽  
Skeletal Muscle Fibres

Cardiovascular effects of treatment with Liraglutide in a population with type 2 diabetes

2013 ◽  
Author(s):  
Marco Zavattaro ◽  
Flavia Prodam ◽  
Mauri Maria Grazia ◽  
Loredana Pagano ◽  
Marina Caputo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Effects

The BMI and skeletal muscle mass as a risk factor of carotid atherosclerosis in patients with type 2 diabetes

2018 ◽  
Author(s):  
Se-Hwa Kim ◽  
Soo-Kyung Kim ◽  
Young-Ju Choi ◽  
Seok-Won Park ◽  
Eun-Jig Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Risk Factor ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Carotid Atherosclerosis

771-P: Protein Intake at Breakfast Contributes to Maintenance of Skeletal Muscle Mass in Japanese Elderly Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 771-P
Author(s):  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
SAKI OKAMOTO ◽  
DAISUKE YABE ◽  
KENTA MUROTANI ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Elderly Patients ◽  
Muscle Mass ◽  
Protein Intake ◽  
Skeletal Muscle Mass ◽  
P Protein ◽  
Japanese Elderly

scholarly journals Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 900
Author(s):  
Krasimir Kostov ◽  
Alexander Blazhev
Keyword(s):  
Type 2 Diabetes ◽  
Serum Levels ◽  
Vascular Wall ◽  
Collagen Iv ◽  
Collagen Type Iv ◽  
Non Invasive ◽  
Type Iv ◽  
Antibody Levels

Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.

scholarly journals Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes

iScience ◽  
2021 ◽  
pp. 102712
Author(s):  
Tiina Öhman ◽  
Jaakko Teppo ◽  
Neeta Datta ◽  
Selina Mäkinen ◽  
Markku Varjosalo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Proteins

scholarly journals Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

scholarly journals Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rasmus J. O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Glucose Homeostasis ◽  
Gene Set ◽  
Branched Chain Amino Acid ◽  
Human Myotubes ◽  
Branched Chain ◽  
The Impact

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

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