What are the effects of insulin on different organs in the body?

Insulin's Multi-Organ Effects

Insulin is the master anabolic hormone that regulates glucose, lipid, and protein metabolism across multiple organ systems by promoting cellular uptake and storage of nutrients while suppressing catabolic processes. 1

Primary Mechanism of Action

Insulin exerts its effects by binding to insulin receptors on target tissues, triggering a cascade that fundamentally shifts metabolism from catabolic to anabolic states across the body. 2 The hormone's actions are tissue-specific but coordinated to maintain energy homeostasis. 1

Effects on Skeletal Muscle

Glucose Metabolism

• Increases glucose transport across cell membranes by recruiting GLUT4 transporters to the cell surface 3
• Stimulates glycolysis through activation of hexokinase and 6-phosphofructokinase 3
• Promotes glycogen synthesis while simultaneously inhibiting glycogen breakdown 4, 3

Protein Metabolism

• Enhances amino acid uptake into muscle cells 4, 3
• Increases protein synthesis rates, contributing to muscle anabolism 4, 3
• Decreases protein degradation, preventing muscle catabolism 4, 3

Lipid Metabolism

• Reduces fatty acid oxidation in muscle tissue 4, 3
• Increases triglyceride uptake from circulation 4, 3

Effects on Liver

Glucose Regulation

• Suppresses hepatic glucose production by inhibiting both glycogenolysis and gluconeogenesis 4, 1
• Stimulates glycogen synthesis to store excess glucose 4
• Works in concert with hyperglycemia to maintain glucose homeostasis after meals 1

Lipid Metabolism

• Increases VLDL formation and secretion 4
• Stimulates cholesterol synthesis 4
• Reduces fatty acid oxidation 4

Critical Caveat

Subcutaneous insulin delivery creates peripheral hyperinsulinemia with relative hepatic insulin deficiency, leading to suboptimal control of hepatic glucose production compared to physiologic portal vein delivery. 5 This imbalance contributes to both weight gain and hypoglycemia risk. 5

Effects on Adipose Tissue

Lipid Storage and Mobilization

• Inhibits lipolysis, dramatically reducing plasma free fatty acid levels 4, 1, 3
• Stimulates fatty acid and triglyceride synthesis (though to a minor extent in humans) 4, 3
• Increases triglyceride uptake from blood into adipocytes 4, 3
• Promotes glucose uptake via GLUT4 translocation 3

Weight Implications

The suppression of lipolysis combined with enhanced nutrient storage explains why intensive insulin therapy consistently causes weight gain, as demonstrated in the DCCT trial where obesity emerged as a treatment-associated consequence. 5

Effects on Vasculature

• Causes vasodilation in muscle, which enhances muscle glucose disposal by increasing blood flow and nutrient delivery 1
• May cause sodium retention and edema, particularly when previously poor metabolic control is rapidly improved with intensified therapy 2

Effects on Kidneys

• Increases renal sodium reabsorption, contributing to fluid retention 5
• Insulin requirements decrease with declining renal function due to reduced insulin clearance 2

Integrated Physiologic Response to Meals

Following food intake, the coordinated insulin response produces four key actions: 1

1. Suppression of endogenous glucose production (primarily hepatic)
2. Stimulation of glucose uptake by muscle, liver, and adipocytes
3. Inhibition of lipolysis leading to decreased plasma FFA, which further enhances hepatic glucose suppression and muscle glucose uptake
4. Vasodilation in muscle contributing to enhanced glucose disposal

Heterogeneous Tissue Responses in Disease States

Insulin Resistance Paradox

In metabolic syndrome and type 2 diabetes, insulin resistance is not uniform across all tissues. 5 Some tissues remain insulin-responsive or even hyperresponsive despite compensatory hyperinsulinemia: 5

• Hyperactive tissues: Increased renal sodium reabsorption, augmented hepatic VLDL synthesis, increased platelet adhesion/aggregation, central obesity 5
• Resistant tissues: Skeletal muscle glucose uptake, hepatic glucose suppression 5

This heterogeneity means blood glucose alone does not reveal the actual metabolic state of various organs, and euglycemia does not guarantee eumetabolism. 5

Cellular Electrolyte Effects

• Promotes potassium entry into cells under normal conditions 6
• Insulin deficiency removes this protective mechanism, allowing potassium to shift extracellularly during hyperosmolar states, potentially causing paradoxical hyperkalemia despite total body potassium depletion 6

Critical Clinical Considerations

Hypoglycemia Risk

Hypoglycemia is the most common adverse effect of insulin therapy. 2 Risk factors include: 2

• Long diabetes duration
• Diabetic neuropathy (blunted warning symptoms)
• Beta-blocker use
• Intensified glycemic control
• Renal or hepatic impairment

Route-Specific Warnings

• Subcutaneous administration only: Intravenous administration of typical subcutaneous doses causes severe hypoglycemia 2
• Intramuscular injection produces faster and more extensive absorption than intended, risking hypoglycemia 2

Injection Site Complications

• Lipohypertrophy develops from repeated injections at the same site due to insulin's adipogenic effects, causing erratic absorption and glycemic variability 5
• Continuous site rotation within anatomic areas (abdomen, thigh, buttock, upper arm) prevents this complication 5

Mitochondrial Effects

Insulin enhances mitochondrial ATP production in skeletal muscle, increases oxidative enzyme activity, and influences mitochondrial function across multiple tissues. 5 Insulin deficiency in type 1 diabetes is associated with mitochondrial dysfunction, reduced ATP respiration, and increased oxidative stress. 5