Hormones Involved in Metabolism

Why This Matters

Metabolism isn't just about "burning calories"—it's a tightly coordinated system of biochemical pathways that your body regulates through hormonal signaling. In Biological Chemistry I, you're being tested on how these hormones work at the molecular level: signal transduction cascades, receptor binding, enzyme activation, and feedback loops. The hormones in this guide don't act in isolation; they form an integrated network that maintains energy homeostasis across fed, fasting, and stress states.

Don't just memorize which hormone does what. Instead, focus on understanding the mechanisms—why does insulin promote glucose uptake? How do antagonistic hormones like insulin and glucagon balance each other? What distinguishes a rapid stress response from a chronic metabolic adjustment? When you can explain the "why" behind each hormone's action, you'll be ready for any FRQ that asks you to trace a metabolic pathway or predict what happens when a hormone system fails.

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Pancreatic Hormones: The Blood Glucose Regulators

The pancreas serves as the body's primary glucose sensor, releasing hormones that maintain blood sugar within a narrow range. These hormones act antagonistically—one raises glucose while the other lowers it—creating a classic example of negative feedback regulation.

Insulin

• Secreted by pancreatic β-cells in response to elevated blood glucose—binds to receptor tyrosine kinases on target cells, triggering a phosphorylation cascade
• Promotes GLUT4 transporter translocation to the cell membrane, facilitating glucose uptake into muscle and adipose tissue
• Anabolic effects include glycogenesis, lipogenesis, and protein synthesis—insulin essentially signals "energy abundance" and promotes storage

Glucagon

• Released by pancreatic α-cells when blood glucose drops—acts primarily on hepatocytes via G-protein coupled receptors
• Stimulates glycogenolysis and gluconeogenesis in the liver, mobilizing glucose from glycogen stores and amino acid precursors
• Activates hormone-sensitive lipase in adipose tissue, promoting lipolysis to provide alternative fuel sources during fasting

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Stress Response Hormones: Acute and Chronic Mobilization

When the body faces stress—whether immediate danger or prolonged challenge—specific hormones override normal metabolic priorities to ensure survival. The key distinction here is temporal: epinephrine acts within seconds, while cortisol produces sustained effects over hours to days.

Epinephrine (Adrenaline)

• Released from adrenal medulla during acute stress—acts within seconds through β-adrenergic receptors linked to cAMP signaling
• Rapidly elevates blood glucose by activating glycogen phosphorylase in liver and muscle tissue
• Enhances lipolysis and cardiac output—prepares the body for immediate physical demands by mobilizing all available energy substrates

Cortisol

• Steroid hormone from the adrenal cortex—crosses cell membranes and binds intracellular receptors that act as transcription factors
• Promotes gluconeogenesis while inhibiting glucose uptake in peripheral tissues, sparing glucose for the brain during prolonged stress
• Catabolic effects on protein and fat—breaks down muscle protein for gluconeogenic substrates and redistributes fat storage

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Thyroid and Growth Hormones: Basal Metabolic Regulators

These hormones set the overall "pace" of metabolism rather than responding to immediate nutrient fluctuations. They regulate basal metabolic rate (BMR) and long-term energy expenditure through changes in gene expression and cellular activity.

Thyroid Hormones (T3 and T4)

• T4 (thyroxine) is converted to active T3 in target tissues—both are iodinated tyrosine derivatives that cross membranes and bind nuclear receptors
• Increase BMR by upregulating $Na^+/K^+$-ATPase activity and mitochondrial uncoupling proteins, generating heat as a metabolic byproduct
• Potentiate the effects of other hormones—enhance tissue sensitivity to catecholamines and are essential for normal growth and neural development

Growth Hormone

• Pulsatile release from the anterior pituitary—secretion peaks during sleep and is stimulated by ghrelin, inhibited by somatostatin
• Promotes protein synthesis and lipolysis while reducing glucose uptake in muscle and fat—creates a "glucose-sparing" effect
• Stimulates IGF-1 production in the liver—many growth-promoting effects are mediated indirectly through this secondary hormone

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Adipose-Derived Hormones: Energy Balance Signals

Fat tissue isn't just storage—it's an endocrine organ that communicates the body's energy status to the brain. These adipokines form long-term feedback loops that regulate appetite and metabolism based on fat reserves.

Leptin

• Secreted by adipocytes in proportion to fat mass—signals to hypothalamic receptors to suppress appetite and increase energy expenditure
• Leptin resistance is a hallmark of obesity—despite high circulating levels, the brain fails to respond, perpetuating overeating
• Regulates reproductive function and immune responses—low leptin (as in starvation) suppresses these energy-expensive systems

Adiponectin

• Paradoxically decreased in obesity despite being produced by fat tissue—levels are inversely correlated with body fat percentage
• Enhances insulin sensitivity by activating AMPK, promoting glucose uptake and fatty acid oxidation in muscle
• Anti-inflammatory and cardioprotective effects—low adiponectin is associated with metabolic syndrome and cardiovascular disease

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Gut Hormones: Nutrient Sensing and Satiety

The gastrointestinal tract releases hormones that coordinate digestion with systemic metabolism. These incretins and appetite regulators create short-term signals that complement the long-term adipokine system.

Ghrelin

• The only known orexigenic (appetite-stimulating) gut hormone—produced primarily by stomach cells when the stomach is empty
• Levels peak before meals and drop after eating—acts on hypothalamic receptors to trigger hunger sensations
• Stimulates growth hormone release from the pituitary—links nutritional status to growth and metabolic regulation

Glucagon-like Peptide-1 (GLP-1)

• Incretin hormone released from intestinal L-cells after eating—enhances glucose-dependent insulin secretion from β-cells
• Inhibits glucagon release and slows gastric emptying—creates a "brake" on glucose absorption and appetite
• Target of diabetes medications (GLP-1 receptor agonists)—understanding its mechanism is clinically relevant and exam-worthy

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Quick Reference Table

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Self-Check Questions

1. Which two hormones form the primary antagonistic pair regulating blood glucose, and what signaling pathways does each use?

2. Compare the mechanisms by which epinephrine and cortisol raise blood glucose—how do their time courses and receptor types differ?

3. Both leptin and adiponectin are secreted by adipose tissue, yet they have opposite relationships with body fat percentage. Explain this paradox and its clinical significance.

4. If a patient has impaired GLP-1 signaling, predict the effects on insulin secretion, glucagon levels, and appetite. Which other hormone might partially compensate?

5. An FRQ asks you to explain how the body maintains blood glucose during a 24-hour fast. Which hormones would you discuss, in what order would they become important, and what metabolic pathways would each activate?