Role of reactive oxygen species in injury-induced insulin resistance

Area of Science:

• Biochemistry
• Metabolic disorders
• Cellular signaling

Background:

• Acute insulin resistance is a common complication of critical illness, injury, and infection.
• The underlying mechanisms, particularly the role of reactive oxygen species (ROS), remain incompletely understood.
• Critical illness can lead to hyperglycemia, a hallmark of diabetes.

Purpose of the Study:

• To investigate the role of reactive oxygen species (ROS) in the development of acute hepatic insulin resistance during critical illness.
• To explore the therapeutic potential of targeting ROS in critical illness-induced diabetes.

Main Methods:

• Measurement of hepatic ROS levels in a mouse model of critical illness.
• Genetic manipulation using superoxide dismutase 2 (SOD2) to reduce mitochondrial ROS.
• Assessment of insulin-induced intracellular signaling pathways and cellular stress signaling (e.g., c-Jun N-terminal kinase).
• Evaluation of glucose metabolism and hyperglycemia.

Main Results:

• Hepatic ROS levels significantly increased following injury in mice.
• Overexpression of superoxide dismutase 2, which reduced ROS, conferred protection against acute hepatic insulin resistance.
• Insulin-induced signaling was impaired, while stress signaling was activated post-injury.
• SOD2 overexpression or antioxidant treatment normalized insulin signaling, stress pathways, and glucose metabolism.

Conclusions:

• Reactive oxygen species (ROS) play a crucial role in mediating acute hepatic insulin resistance and hyperglycemia during critical illness.
• Targeting ROS with interventions like superoxide dismutase 2 or antioxidants holds promise for treating critical illness diabetes.