Pathophysiology
Clinical meaning
Glucose homeostasis is maintained by a precise hormonal feedback system centered on insulin (the primary hypoglycemic hormone) and glucagon (the primary hyperglycemic hormone), both produced by the pancreatic islets of Langerhans. Understanding this dynamic system is essential for NP management of diabetes, hypoglycemia, and metabolic emergencies. Insulin is synthesized by pancreatic beta cells as preproinsulin, cleaved to proinsulin in the endoplasmic reticulum, and then cleaved to mature insulin plus C-peptide in secretory granules. C-peptide is released in equimolar amounts with insulin and serves as a clinical marker of endogenous insulin production (undetectable in type 1 diabetes, elevated in early type 2 diabetes and insulinoma). Insulin secretion occurs in two phases: first phase (rapid release of preformed insulin granules within 5-10 minutes of glucose exposure, lost early in type 2 diabetes) and second phase (sustained release of newly synthesized insulin proportional to glucose level). Glucose enters beta cells via GLUT2 transporters, is metabolized through glycolysis and the TCA cycle producing ATP, which closes ATP-sensitive potassium channels (K-ATP channels โ the target of sulfonylurea drugs), depolarizing the beta cell membrane, opening voltage-gated...