scholarly journals Response to Comment on Sato et al. Improving Type 2 Diabetes Through a Distinct Adrenergic Signaling Pathway Involving mTORC2 That Mediates Glucose Uptake in Skeletal Muscle. Diabetes 2014;63:4115-4129

Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. e22-e23 ◽  
Author(s):  
M. Sato ◽  
N. Dehvari ◽  
A. I. Oberg ◽  
R. J. Summers ◽  
D. S. Hutchinson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Adrenergic Signaling

scholarly journals Improving Type 2 Diabetes Through a Distinct Adrenergic Signaling Pathway Involving mTORC2 That Mediates Glucose Uptake in Skeletal Muscle

Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. 4115-4129 ◽  
Author(s):  
M. Sato ◽  
N. Dehvari ◽  
A. I. Oberg ◽  
O. S. Dallner ◽  
A. L. Sandstrom ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Adrenergic Signaling

Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells

2014 ◽  
Vol 306 (9) ◽  
pp. E1065-E1076 ◽  
Author(s):  
Hidemitsu Sakagami ◽  
Yuichi Makino ◽  
Katsutoshi Mizumoto ◽  
Tsubasa Isoe ◽  
Yasutaka Takeda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation

Defects in glucose uptake by the skeletal muscle cause diseases linked to metabolic disturbance such as type 2 diabetes. The molecular mechanism determining glucose disposal in the skeletal muscle in response to cellular stimuli including insulin, however, remains largely unknown. The hypoxia-inducible factor-1α (HIF-1α) is a transcription factor operating in the cellular adaptive response to hypoxic conditions. Recent studies have uncovered pleiotropic actions of HIF-1α in the homeostatic response to various cellular stimuli, including insulin under normoxic conditions. Thus we hypothesized HIF-1α is involved in the regulation of glucose metabolism stimulated by insulin in the skeletal muscle. To this end, we generated C2C12myocytes in which HIF-1α is knocked down by short-hairpin RNA and examined the intracellular signaling cascade and glucose uptake subsequent to insulin stimulation. Knockdown of HIF-1α expression in the skeletal muscle cells resulted in abrogation of insulin-stimulated glucose uptake associated with impaired mobilization of glucose transporter 4 (GLUT4) to the plasma membrane. Such defect seemed to be caused by reduced phosphorylation of the protein kinase B substrate of 160 kDa (AS160). AS160 phosphorylation and GLUT4 translocation by AMP-activated protein kinase activation were abrogated as well. In addition, expression of the constitutively active mutant of HIF-1α (CA-HIF-1α) or upregulation of endogenous HIF-1α in C2C12cells shows AS160 phosphorylation comparable to the insulin-stimulated level even in the absence of insulin. Accordingly GLUT4 translocation was increased in the cells expressing CA-HIF1α. Taken together, HIF-1α is a determinant for GLUT4-mediated glucose uptake in the skeletal muscle cells thus as a possible target to alleviate impaired glucose metabolism in, e.g., type 2 diabetes.

The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective

Metabolism ◽  
2015 ◽  
Vol 64 (12) ◽  
pp. 1619-1628 ◽  
Author(s):  
Júlia Matzenbacher dos Santos ◽  
Marcos Lazaro Moreli ◽  
Shikha Tewari ◽  
Sandra Aparecida Benite-Ribeiro
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Skeletal Muscle Glucose Uptake

scholarly journals Fridamycin A, a Microbial Natural Product, Stimulates Glucose Uptake without Inducing Adipogenesis

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 765 ◽  
Author(s):  
Sun-Young Yoon ◽  
Seoung Rak Lee ◽  
Ji Young Hwang ◽  
René Benndorf ◽  
Christine Beemelmanns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Polyketide Synthase ◽  
Term Treatment ◽  
Ampk Signaling ◽  
Microbial Product ◽  
Long Term Treatment

Type 2 diabetes is a complex, heterogeneous, and polygenic disease. Currently, available drugs for treating type 2 diabetes predominantly include sulfonylureas, α-glucosidase inhibitors, and biguanides. However, long-term treatment with these therapeutic drugs is often accompanied by undesirable side effects, which have driven interest in the development of more effective and safer antidiabetic agents. To address the urgent need for new chemical solutions, we focused on the analysis of structurally novel and/or biologically new metabolites produced by insect-associated microbes as they have recently been recognized as a rich source of natural products. Comparative LC/MS-based analysis of Actinomadura sp. RB99, isolated from a fungus-growing termite, led to the identification of the type II polyketide synthase-derived fridamycin A. The structure of fridamycin A was confirmed by 1H NMR data and LC/MS analysis. The natural microbial product, fridamycin A, was examined for its antidiabetic properties in 3T3-L1 adipocytes, which demonstrated that fridamycin A induced glucose uptake in 3T3-L1 cells by activating the AMP-activated protein kinase (AMPK) signaling pathway but did not affect adipocyte differentiation, suggesting that the glucose uptake took place through activation of the AMPK signaling pathway without inducing adipogenesis. Our results suggest that fridamycin A has potential to induce fewer side effects such as weight gain compared to rosiglitazone, a commonly used antidiabetic drug, and that fridamycin A could be a novel potential therapeutic candidate for the management of type 2 diabetes.

scholarly journals Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

2014 ◽  
Vol 38 (4) ◽  
pp. 308-314 ◽  
Author(s):  
Kristin I. Stanford ◽  
Laurie J. Goodyear
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Whole Body ◽  
Metabolic Genes ◽  
Increase Glucose Uptake ◽  
Glucose Transporter Proteins

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial function, increases mitochondrial biogenesis, and increases the expression of glucose transporter proteins and numerous metabolic genes. This review focuses on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle.

SKELETAL MUSCLE GLUT1 TRANSPORTER PROTEIN AND BASAL LEG GLUCOSE UPTAKE IS REDUCED IN TYPE 2 DIABETES.

2004 ◽  
Vol 52 ◽  
pp. S106
Author(s):  
T. P. Ciaraldi ◽  
S. Mudaliar ◽  
J. A. Macievic ◽  
A. Barzin ◽  
S. V. Edelman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Transporter Protein

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 Rosiglitazone but Not Metformin Enhances Insulin- and Exercise-Stimulated Skeletal Muscle Glucose Uptake in Patients With Newly Diagnosed Type 2 Diabetes

Diabetes ◽  
2002 ◽  
Vol 51 (12) ◽  
pp. 3479-3485 ◽  
Author(s):  
K. Hallsten ◽  
K. A. Virtanen ◽  
F. Lonnqvist ◽  
H. Sipila ◽  
A. Oksanen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Newly Diagnosed ◽  
Skeletal Muscle Glucose Uptake
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