[Pathophysiology of insulin resistance]

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Diseases

Context:

• Type 2 diabetes is characterized by insulin resistance in muscle, liver, and fat, alongside impaired insulin secretion.
• Skeletal muscle insulin resistance is increasingly recognized as an early and critical factor in Type 2 diabetes pathogenesis.

Purpose:

• To review current knowledge on abnormalities in skeletal muscle insulin signaling pathways in Type 2 diabetes and pre-diabetes.
• To differentiate between secondary effects and potential primary molecular defects contributing to insulin resistance.

Summary:

• Investigates defects in insulin receptor, phosphatases, glycogen synthase, and glucose transporters in skeletal muscle.
• Examines abnormalities in pre-diabetic and Type 2 diabetic individuals, classifying them as secondary or primary molecular defects.
• Discusses compensatory hyperinsulinemia in early stages and declining insulin secretion leading to overt Type 2 diabetes, with underlying molecular mechanisms still under investigation.

Impact:

• Highlights the crucial role of skeletal muscle insulin signaling in the development of Type 2 diabetes.
• Provides insights into potential molecular targets for early intervention in pre-diabetic states.
• Underscores the need for further research into the molecular mechanisms of declining insulin secretion.