Pancreatic Physiology: Exocrine Digestion and Endocrine Glucose Regulation

The pancreas is a dual-function organ: exocrine (digestive enzyme secretion) and endocrine (hormonal glucose homeostasis).

Exocrine Function: Digestive Enzyme Production

Acinar cells synthesize and secrete inactive zymogens into the ductal system → duodenum. Activation occurs in the intestinal lumen.

Key Enzymes

• Proteolytic: Trypsinogen → trypsin (enteropeptidase-activated); activates chymotrypsinogen, proelastase, procarboxypeptidases. Digest proteins → peptides/amino acids.
• Amylase: Hydrolyzes starch/glycogen → maltose, maltotriose, α-limit dextrins. No salivary amylase in some mammals (pancreatic amylase essential).
• Lipase: Hydrolyzes triglycerides → 2-monoglyceride + 2 fatty acids. Requires colipase (prevents bile salt inhibition) and bile salt micelles for interfacial activation.
• Nucleases: DNase, RNase → nucleotides

Ductal Secretion

Centroacinar/ductal cells secrete HCO₃⁻-rich fluid (pH 8) — neutralizes gastric acid, optimizes enzyme pH.

Endocrine Function: Islets of Langerhans

• β-cells (50-70%): Insulin — promotes glucose uptake (GLUT4), glycogen synthesis, lipogenesis, protein synthesis
• α-cells (20-30%): Glucagon — glycogenolysis, gluconeogenesis, ketogenesis
• δ-cells (<10%): Somatostatin — inhibits insulin/glucagon/GI hormones
• PP-cells: Pancreatic polypeptide — regulates exocrine secretion, appetite
• ε-cells: Ghrelin — hunger stimulation (fetal/neonatal predominance)

Glucose Homeostasis

Insulin/glucagon ratio determines metabolic state. Portal venous drainage delivers hormones directly to liver (first-pass hepatic extraction: 50% insulin, minimal glucagon).

Clinical Correlates

• Exocrine insufficiency: Chronic pancreatitis, CF, pancreatic cancer → steatorrhea, weight loss, fat-soluble vitamin deficiency → PERT (pancreatic enzyme replacement therapy)
• Diabetes mellitus: Type 1 (β-cell destruction), Type 2 (insulin resistance + β-cell failure), Type 3c (pancreatogenic)
• Acute pancreatitis: Premature intrapancreatic zymogen activation → autodigestion