Exocrine Pancreatic Function
The exocrine pancreas produces ~1.5 L/day of bicarbonate-rich juice and digestive enzymes, secreted into the pancreatic duct → duodenum. Regulated by CCK and secretin.
| Enzyme | Form Secreted | Activated By | Substrate |
|---|---|---|---|
| Trypsinogen | Zymogen (inactive) | Enterokinase (brush border) | Proteins (endopeptidase) |
| Chymotrypsinogen | Zymogen | Trypsin | Aromatic amino acids |
| Elastase | Zymogen | Trypsin | Elastin and connective tissue proteins |
| Pancreatic lipase | Active | — | Triglycerides (requires colipase and bile salts) |
| Pancreatic amylase | Active | — | Starch (polysaccharides) |
| Bicarbonate | Secreted by ductal cells | Secretin | Neutralizes gastric acid in duodenum (optimal pH for enzymes) |
🩹 Pancreatitis MechanismPremature activation of trypsinogen within pancreas → autodigestion. Causes: gallstones (most common in women), alcohol (most common in men), hypertriglyceridemia, hypercalcemia, ERCP, medications, trauma, idiopathic. Trypsin activates all other zymogens → cascade damage.
Endocrine Pancreas — Islets of Langerhans
| Cell Type | Percentage | Hormone | Stimulus |
|---|---|---|---|
| Beta cells | 70% | Insulin, C-peptide, amylin | Glucose, amino acids, GIP, GLP-1, vagal (ACh) |
| Alpha cells | 20% | Glucagon | Hypoglycemia, amino acids, stress, fasting |
| Delta cells | 5% | Somatostatin | Glucose, fatty acids, GLP-1 — inhibits alpha and beta cells |
| PP cells | 5% | Pancreatic polypeptide | Protein; inhibits pancreatic exocrine secretion |
Insulin Physiology
Insulin is the primary anabolic hormone. Released in biphasic pattern: first phase (preformed insulin, within 2-5 min of glucose) and second phase (new insulin synthesis, over 30-60 min).
| Target | Insulin Effect |
|---|---|
| Liver | Glycogenesis, glycolysis, lipogenesis; inhibits gluconeogenesis and glycogenolysis |
| Muscle | Glucose uptake (GLUT4), glycogenesis, protein synthesis |
| Adipose | Glucose uptake (GLUT4), lipogenesis (triglyceride storage), inhibits lipolysis and HSL |
| Electrolytes | Drives K+ into cells (used in hyperkalemia treatment); also Mg2+ and PO4- |
⭐ C-Peptide Clinical UseC-peptide is co-secreted with insulin in equimolar amounts. Low C-peptide + high insulin = exogenous insulin injection (malingering/factitious). High C-peptide + high insulin = insulinoma. Used to distinguish endogenous vs. exogenous hyperinsulinism.
Glucagon and Counter-Regulatory Hormones
| Hormone | Source | Effect on Blood Glucose | Key Mechanism |
|---|---|---|---|
| Glucagon | Alpha cells | Raises | Hepatic glycogenolysis + gluconeogenesis; lipolysis; ketogenesis |
| Epinephrine | Adrenal medulla | Raises | Glycogenolysis (liver + muscle); lipolysis; inhibits insulin secretion (alpha-2) |
| Cortisol | Adrenal cortex | Raises | Gluconeogenesis; insulin resistance; protein catabolism |
| Growth hormone | Anterior pituitary | Raises | Insulin resistance; lipolysis; "dawn phenomenon" |
🧐 Counter-Regulatory Hormones"GECC" — Glucagon, Epinephrine, Cortisol, GH — all raise blood glucose. All are catabolic except GH (anabolic in other tissues). Deficiency of all four = profound hypoglycemia (as in adrenal insufficiency).
Clinical Pearls
⭐ Incretin EffectOral glucose raises insulin more than IV glucose (same dose) — the "incretin effect." GIP (gastric inhibitory peptide) from K cells and GLP-1 from L cells are released with oral nutrients → potentiate glucose-stimulated insulin secretion. GLP-1 agonists (semaglutide, liraglutide) and DPP-4 inhibitors exploit this mechanism.
🩹 Whipple's TriadCriteria for insulinoma (or any hypoglycemia disorder): (1) symptoms of hypoglycemia, (2) low blood glucose during symptoms, (3) relief with glucose administration. Insulinoma: most common pancreatic endocrine tumor; usually benign, solitary; diagnosed with 72-hour fast + insulin and C-peptide levels.