Induction of insulin resistance in human skeletal muscle cells by downregulation of glycogen synthase protein expression

Metabolism ◽  
2000 ◽  
Vol 49 (8) ◽  
pp. 962-968 ◽  
Author(s):  
K.S. Park ◽  
T.P. Ciaraldi ◽  
L. Carter ◽  
S. Mudaliar ◽  
S.E. Nikoulina ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

scholarly journals Metformin Increases Protein Phosphatase 2A Activity in Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Aktham Mestareehi ◽  
Xiangmin Zhang ◽  
Berhane Seyoum ◽  
Zaher Msallaty ◽  
Abdullah Mallisho ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Protein Phosphatase ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells ◽  
Phosphatase 2A ◽  
Sensitivity Improvement

Context. Skeletal muscle insulin resistance is one of the primary contributors of type 2 diabetes (T2D). Metformin is the first-line drug for the treatment of T2D. The primary effects of metformin include decreasing glucose production in the liver and decreasing insulin resistance in the skeletal muscle. However, the molecular mechanism of metformin’s action in skeletal muscle is not well understood. Protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, plays a pivotal role in cellular processes, such as signal transduction, cell proliferation, and apoptosis, and acts through dephosphorylating key signaling molecules such as AKT and AMPK. However, whether PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells remains to be elucidated. Objective. To investigate if PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells. Participants. Eight lean insulin-sensitive nondiabetic participants (4 females and 4 males; age: 21.0 ± 1.0 years; BMI: 22.0 ± 0.7   kg / m 2 ; 2-hour OGTT: 97.0 ± 6.0   mg / dl ; HbA1c: 5.3 ± 0.1 % ; fasting plasma glucose: 87.0 ± 2.0   mg / dl ; M value; 11.0 ± 1.0   mg / kgBW / min ). Design. A hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity in human subjects, and skeletal muscle biopsy samples were obtained. Primary human skeletal muscle cells (shown to retain metabolic characteristics of donors) were cultured from these muscle biopsies that included 8 lean insulin-sensitive participants. Cultured cells were expanded, differentiated into myotubes, and treated with 50 μM metformin for 24 hours before harvesting. PP2Ac activity was measured by a phosphatase activity assay kit (Millipore) according to the manufacturer’s protocol. Results. The results indicated that metformin significantly increased the activity of PP2A in the myotubes for all 8 lean insulin-sensitive nondiabetic participants, and the average fold increase is 1.54 ± 0.11 ( P < 0.001 ). Conclusions. These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin’s action in skeletal muscle in humans.

scholarly journals Chemerin Is a Novel Adipocyte-Derived Factor Inducing Insulin Resistance in Primary Human Skeletal Muscle Cells

Diabetes ◽  
2009 ◽  
Vol 58 (12) ◽  
pp. 2731-2740 ◽  
Author(s):  
Henrike Sell ◽  
Jurga Laurencikiene ◽  
Annika Taube ◽  
Kristin Eckardt ◽  
Andrea Cramer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

scholarly journals Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

Molecules ◽  
2015 ◽  
Vol 20 (5) ◽  
pp. 8242-8269 ◽  
Author(s):  
Mohamad Abu Bakar ◽  
Kian-Kai Cheng ◽  
Mohamad Sarmidi ◽  
Harisun Yaakob ◽  
Hasniza Huri
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Antimycin A ◽  
Human Skeletal Muscle Cells

scholarly journals Role of Glycogen Synthase Kinase-3α in Insulin Action in Cultured Human Skeletal Muscle Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (9) ◽  
pp. 4393-4399 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Svetlana E. Nikoulina ◽  
Rahil A. Bandukwala ◽  
Leslie Carter ◽  
Robert R. Henry
Keyword(s):  
Skeletal Muscle ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glycogen Synthase Kinase ◽  
Human Skeletal Muscle Cells
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