PHYSIOLOGICAL ROLES OF THE LIVER AND PANCREAS: INTEGRATED FUNCTIONS IN METABOLISM, DIGESTION, ENDOCRINE REGULATION, AND DETOXIFICATION

The liver and pancreas are the two largest accessory digestive glands in the human body and among the most metabolically versatile organs. The liver, weighing approximately 1.5 kg and receiving a dual blood supply from the portal vein and hepatic artery, performs over 500 distinct physiological functions. The pancreas, a mixed exocrine–endocrine gland of approximately 80–100 g, produces digestive enzymes that hydrolyze all major macronutrients and secretes the hormones insulin, glucagon, and somatostatin that maintain blood glucose homeostasis. Dysregulation of either organ underlies some of the most common and lethal diseases encountered in clinical medicine, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, diabetes mellitus, and pancreatic adenocarcinoma. Objective: To provide a comprehensive, evidence-based review of the integrated physiological roles of the liver and pancreas, including their roles in macronutrient metabolism, bile acid physiology, detoxification, endocrine regulation of glucose homeostasis, and the pathophysiological consequences of organ dysfunction. Methods: A systematic review of eight primary peer-reviewed sources was conducted, encompassing original research articles, authoritative textbooks, meta-analyses, and clinical guidelines published between 1998 and 2024. Results: Hepatocytes, the principal parenchymal cells of the liver, perform glycogenesis, gluconeogenesis, fatty acid oxidation, urea synthesis, bile acid conjugation, and phase I/II biotransformation of xenobiotics via the cytochrome P450 (CYP) enzyme system. The exocrine pancreas secretes 1.5–2.5 L of bicarbonate-rich fluid daily containing proteases (trypsinogen, chymotrypsinogen), lipases, and amylases, regulated by cholecystokinin (CCK) and secretin. Pancreatic β-cells release insulin in a biphasic pattern in response to glucose, while α-cells secrete glucagon during hypoglycemia, and δ-cells release somatostatin to modulate both. The enteroinsular axis, mediated by GLP-1 and GIP incretin hormones, amplifies postprandial insulin secretion by 50–70% of the total insulin response. Conclusion: The liver and pancreas operate as a functionally integrated unit, coordinating nutrient absorption, macronutrient metabolism, and glucose homeostasis through hormonal, neural, and paracrine signaling networks. Understanding their physiological interdependence is essential for the rational management of metabolic, digestive, and endocrine disorders.