Investigating the Role of Mitochondria in Type 2 Diabetes – Lessons from Lipidomics and Proteomics Studies of Skeletal Muscle and Liver

2019 ◽  
pp. 143-182 ◽  
Author(s):  
Lisa Kappler ◽  
Laxmikanth Kollipara ◽  
Rainer Lehmann ◽  
Albert Sickmann
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle

scholarly journals 1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

2021 ◽  
Vol 12 ◽  
Author(s):  
Duyen Tran ◽  
Stephen Myers ◽  
Courtney McGowan ◽  
Darren Henstridge ◽  
Rajaraman Eri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Muscle Dysfunction ◽  
Dependent Manner

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. In vitro studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of in vitro assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.

scholarly journals DIABETES MELLITUS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S574-S574
Author(s):  
Steven J Prior
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Metabolism ◽  
Metabolic Abnormalities ◽  
Metabolic Inflexibility ◽  
Muscle Changes ◽  
And Function

Abstract Nearly three-fourths of adults over 65 year of age are affected by impaired glucose tolerance or type 2 diabetes. Both aging and inactivity contribute to the numerous skeletal muscle changes that occur with insulin resistance and type 2 diabetes. These changes include reduced capillarization that can impaired glucose uptake and substrate delivery, resulting in metabolic abnormalities and metabolic inflexibility. These changes may ultimately contribute to reduced delivery of oxygen, nutrients, and hormones to the muscles leading to impairments in metabolism, muscle mass, and function. We will discuss current research on the role of vascular impairments and reduced skeletal muscle capillarization in the development of impaired muscle metabolism, fitness and function. Finally, we will discuss how exercise training may reverse these declines.

scholarly journals Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes

Diabetes ◽  
2000 ◽  
Vol 49 (2) ◽  
pp. 263-271 ◽  
Author(s):  
S. E. Nikoulina ◽  
T. P. Ciaraldi ◽  
S. Mudaliar ◽  
P. Mohideen ◽  
L. Carter ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Potential Role ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3 ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

scholarly journals Role of Exercise-Induced Calmodulin Protein Kinase (CaMK)II Activation in the Regulation of Omega-6 Fatty Acids and Lipid Metabolism Genes in Rat Skeletal Muscle

2017 ◽  
pp. 969-977 ◽  
Author(s):  
J. S. JOSEPH ◽  
A. O. AYELESO ◽  
E. MUKWEVHO
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Rat Skeletal Muscle ◽  
Exercise Induced ◽  
Diabetes And Obesity ◽  
Camkii Activation

Activation of calmodulin dependent protein kinase (CaMK)II by exercise is beneficial in controlling membrane lipids associated with type 2 diabetes and obesity. Regulation of lipid metabolism is crucial in the improvement of type 2 diabetes and obesity associated symptoms. The role of CaMKII in membrane associated lipid metabolism was the focus of this study. Five to six weeks old male Wistar rats were used in this study. GC×GC-TOFMS technique was used to determine the levels of polyunsaturated fatty acids (linoleic acid, arachidonic acid and 11,14-eicosadienoic acid). Carnitine palmitoyltransferase (Cpt-1) and acetyl-CoA carboxylase (Acc-1) genes expression were assessed using quantitative real time PCR (qPCR). From the results, CaMKII activation by exercise increased the levels of arachidonic acid and 11,14-eicosadienoic acid while a decrease in the level of linolenic acid was observed in the skeletal muscle. The results indicated that exercise-induced CaMKII activation increased CPT-1 expression and decreased ACC-1 expression in rat skeletal muscle. All the observed increases with activation of CaMKII by exercise were aborted when KN93, an inhibitor of CaMKII was injected in exercising rats. This study demonstrated that CaMKII activation by exercise regulated lipid metabolism. This study suggests that CaMKII can be a vital target of therapeutic approach in the management of diseases such as type 2 diabetes and obesity that have increased to epidemic proportions recently.

scholarly journals Insulin sensitisation affects lipoprotein lipase transport in type 2 diabetes: role of adipose tissue and skeletal muscle in response to rosiglitazone

Diabetologia ◽  
2006 ◽  
Vol 49 (10) ◽  
pp. 2412-2418 ◽  
Author(s):  
G. D. Tan ◽  
G. Olivecrona ◽  
H. Vidal ◽  
K. N. Frayn ◽  
F. Karpe
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipoprotein Lipase

scholarly journals Bisphenols and the Development of Type 2 Diabetes: The Role of the Skeletal Muscle and Adipose Tissue

Environments ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 35
Author(s):  
Fozia Ahmed ◽  
Maria João Pereira ◽  
Céline Aguer
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Bisphenol A ◽  
Cross Talk ◽  
Environmental Contaminants ◽  
Bisphenol S

Bisphenol A (BPA) and bisphenol S (BPS) are environmental contaminants that have been associated with the development of insulin resistance and type 2 diabetes (T2D). Two organs that are often implicated in the development of insulin resistance are the skeletal muscle and the adipose tissue, however, seldom studies have investigated the effects of bisphenols on their metabolism. In this review we discuss metabolic perturbations that occur in both the skeletal muscle and adipose tissue affected with insulin resistance, and how exposure to BPA or BPS has been linked to these changes. Furthermore, we highlight the possible effects of BPA on the cross-talk between the skeletal muscle and adipose tissue.

The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes

2018 ◽  
Vol 449 (1-2) ◽  
pp. 251-255 ◽  
Author(s):  
Julia Matzenbacher dos Santos ◽  
Denise Silva de Oliveira ◽  
Marcos Lazaro Moreli ◽  
Sandra Aparecida Benite-Ribeiro
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Mitochondrial Dna Damage

scholarly journals Diacylglycerol kinase-δ regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics

2016 ◽  
Vol 310 (1) ◽  
pp. E51-E60 ◽  
Author(s):  
Lake Q. Jiang ◽  
Thais de Castro Barbosa ◽  
Julie Massart ◽  
Atul S. Deshmukh ◽  
Lars Löfgren ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Signal Transduction ◽  
Lipid Metabolism ◽  
Lipid Oxidation ◽  
Diacylglycerol Kinase ◽  
Muscle Energetics ◽  
Ampk Signaling

Decrease of AMPK-related signal transduction and insufficient lipid oxidation contributes to the pathogenesis of obesity and type 2 diabetes. Previously, we identified that diacylglycerol kinase-δ (DGKδ), an enzyme involved in triglyceride biosynthesis, is reduced in skeletal muscle from type 2 diabetic patients. Here, we tested the hypothesis that DGKδ plays a role in maintaining appropriate AMPK action in skeletal muscle and energetic aspects of contraction. Voluntary running activity was reduced in DGKδ+/−mice, but glycogen content and mitochondrial markers were unaltered, suggesting that DGKδ deficiency affects skeletal muscle energetics but not mitochondrial protein abundance. We next determined the role of DGKδ in AMPK-related signal transduction and lipid metabolism in isolated skeletal muscle. AMPK activation and signaling were reduced in DGKδ+/−mice, concomitant with impaired lipid oxidation and elevated incorporation of free fatty acids into triglycerides. Strikingly, DGKδ deficiency impaired work performance, as evident by altered force production and relaxation dynamics in response to repeated contractions. In conclusion, DGKδ deficiency impairs AMPK signaling and lipid metabolism, thereby highlighting the deleterious role of excessive lipid metabolites in the development of peripheral insulin resistance and type 2 diabetes pathogenesis. DGKδ deficiency also influences skeletal muscle energetics, which may lead to low physical activity levels in type 2 diabetes.

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