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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
Published on: June 25, 2017
Hyperglycemia and insulin resistance: possible mechanisms
Eva Tomás1, Yen-Shou Lin, Zeina Dagher
1Diabetes and Metabolism Research Unit, Department of Medicine, and Section of Endocrinology, Boston University School of Medicine, Massachusetts 02118, USA.
Annals of the New York Academy of Sciences
|June 25, 2002
Summary
Sustained hyperglycemia causes insulin resistance by impairing glucose utilization and glycogen synthesis in muscle and other cells. AMP-activated protein kinase (AMPK) activation may prevent these negative effects.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Syndrome
Background:
- Sustained hyperglycemia leads to glucose toxicity, impairing insulin action in skeletal muscle.
- Insulin resistance is a hallmark of type 2 diabetes and metabolic disorders.
- Hyperglycemia affects glucose metabolism and signaling pathways in various cell types.
Purpose of the Study:
- To investigate the effects of hyperglycemia on insulin signaling and glucose metabolism in rat skeletal muscle (EDL) and human umbilical vein endothelial cells (HUVEC).
- To explore the role of ceramide and AMP-activated protein kinase (AMPK) in hyperglycemia-induced insulin resistance.
Main Methods:
- Incubation of rat EDL muscle and HUVEC in hyperglycemic conditions (25 mM glucose).
- Measurement of glucose incorporation into glycogen.
- Assessment of Akt/PKB and PI3-kinase activation.
- Analysis of ceramide and diacylglycerol levels.
- Evaluation of apoptosis and the effect of AICAR (AMPK activator).
Main Results:
- Hyperglycemia impaired insulin-stimulated glucose incorporation into glycogen and Akt/PKB activation in rat EDL muscle.
- No increase in ceramide mass was observed in hyperglycemic EDL muscle.
- Hyperglycemia induced insulin resistance, increased apoptosis, and impaired Akt activation in HUVEC.
- These effects in HUVEC were prevented by AICAR, suggesting a role for AMPK.
Conclusions:
- Hyperglycemia induces insulin resistance in non-classical insulin target tissues like HUVEC, beyond its effects on skeletal muscle.
- Impaired Akt activation is a common feature of hyperglycemia-induced insulin resistance.
- AMPK activation shows potential in preventing or reversing hyperglycemia-induced cellular dysfunction and insulin resistance.
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