The pancreas plays a crucial role in regulating blood glucose levels through its endocrine function. Pancreatic islets, scattered throughout the organ, contain specialized cells that secrete hormones like insulin and glucagon to maintain glucose homeostasis.

Insulin and glucagon work in tandem to keep blood sugar balanced. When glucose levels rise, beta cells release insulin to promote glucose uptake and storage. Conversely, when glucose levels drop, alpha cells secrete glucagon to increase blood sugar.

Pancreatic Islets and Glucose Regulation

Structure of pancreatic islets

• Pancreatic islets (islets of Langerhans) are clusters of endocrine cells scattered throughout the pancreas constitute 1-2% of the pancreatic mass
• Contain several cell types that secrete different hormones (insulin, glucagon, somatostatin, pancreatic polypeptide)
  • Alpha cells (α cells) comprise 15-20% of the islet cells secrete glucagon stimulates glycogenolysis and gluconeogenesis in the liver increasing blood glucose levels
  • Beta cells (β cells) most abundant cell type in the islets (65-80%) stimulated by high blood glucose levels to release insulin promotes glucose uptake by cells and storage of glucose as glycogen decreasing blood glucose levels
    • Beta cells also produce amylin, which helps regulate glucose metabolism by slowing gastric emptying and promoting satiety
  • Delta cells (δ cells) comprise 3-10% of the islet cells secrete somatostatin inhibits the secretion of insulin and glucagon
  • PP cells (F cells) comprise 1% of the islet cells secrete pancreatic polypeptide regulates pancreatic exocrine and endocrine secretion

Insulin and glucagon in glucose regulation

• Insulin lowers blood glucose levels by:
  1. Stimulating glucose uptake by skeletal muscle and adipose tissue via GLUT4 glucose transporters
  2. Promoting glycogenesis (conversion of glucose to glycogen) in the liver and muscle
  3. Inhibiting gluconeogenesis and glycogenolysis in the liver
  4. Enhancing lipogenesis and protein synthesis
• Glucagon increases blood glucose levels by:
  1. Stimulating glycogenolysis in the liver releasing glucose into the bloodstream
  2. Promoting gluconeogenesis in the liver producing glucose from non-carbohydrate sources (amino acids, lipids)
  3. Enhancing lipolysis in adipose tissue providing energy substrates for gluconeogenesis
• Insulin and glucagon work together to maintain blood glucose homeostasis
  • Insulin-to-glucagon ratio determines the net effect on blood glucose levels
    • High insulin-to-glucagon ratio favors glucose storage and utilization lowering blood glucose
    • Low insulin-to-glucagon ratio favors glucose production and release raising blood glucose

Effects of pancreatic hormones

• Somatostatin:
  • Inhibits the secretion of insulin and glucagon from pancreatic islets
  • Suppresses the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) from the anterior pituitary
  • Reduces the secretion of gastrin, cholecystokinin (CCK), and secretin from the gastrointestinal tract decreasing gastrointestinal motility and nutrient absorption
• Pancreatic polypeptide (PP):
  • Inhibits pancreatic exocrine secretion of digestive enzymes
  • Reduces gallbladder contraction and bile secretion
  • Slows gastric emptying and intestinal motility
  • Suppresses appetite by acting on the hypothalamus
  • Modulates the secretion of other pancreatic hormones (insulin, glucagon) but the exact effects are not well understood

Incretin hormones and glucose regulation

• Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that enhance insulin secretion in response to glucose
• These hormones are released by intestinal cells in response to food intake and play a crucial role in glucose homeostasis
• Incretins also inhibit glucagon secretion, slow gastric emptying, and promote satiety

Diabetes mellitus

• Type 1 diabetes mellitus is an autoimmune disorder characterized by destruction of pancreatic beta cells, leading to insulin deficiency
• Type 2 diabetes mellitus is characterized by insulin resistance and/or decreased insulin production, often associated with obesity and lifestyle factors