unit 5, lesson 6: Endocrine Pancreas

• PH1124 Unit 5 Lecture 6 covers the endocrine pancreas, including its anatomy, the secretion and actions of insulin and glucagon, and the main disorder associated with it, Diabetes Mellitus.
• Learning outcomes include describing the anatomy of the pancreas and understanding the roles of insulin and glucagon in regulating glucose levels.

Homeostatic Control of Metabolism

• Glucose acts as the primary substrate for ATP production.
• Glucose levels are controlled by insulin and glucagon, 2 hormones secreted by endocrine cells of the pancreas.
• Blood glucose levels are regulated by the ratio of insulin to glucagon.
• These hormones are secreted on demand and have short half lives.
• They act antagonistically to maintain plasma glucose concentrations within the normal range of 4-7.8 mmol/l.

Anatomy of the Pancreas

• The cells of the islets of Langerhans constitute the endocrine pancreas.
• α cells secrete glucagon.
• β cells secrete insulin and amylin.
• D cells secrete somatostatin.

Glycogenesis

• Glycogenesis is the process of converting glucose to glycogen for storage, requiring energy.
• Glycogen synthase and branching enzymes are involved in Glycogenesis.

Glycogenolysis

• Glycogenolysis is the breakdown of stored glycogen into glucose.
• Glycogen phosphorylase, debrancher enzyme, and phosphoglucomutase are involved in Glycogenolysis, ultimately producing Glucose-6-Phosphate, which is then converted to glucose by Glucose-6-Phosphatase.

Insulin Secretion

• Insulin is stored in granules in the cytoplasm of β-cells.
• A rise in blood glucose detected by β-cells triggers insulin secretion.
• Insulin secretion is biphasic, involving the immediate release of stored insulin, followed by the subsequent release of newly synthesized insulin.
• Insulin secretion is affected by the incretin effect related to other materials on the GI tract.

Insulin Actions

• Insulin lowers blood glucose levels by helping glucose move into cells via glucose transporters and stimulating biochemical activity in cells.
• Insulin acts on insulin tyrosine kinase receptors.

Metabolism of Insulin

• Insulin is metabolized by the kidneys and liver, each accounting for about 50%.
• Insulin has a half-life of about 5 minutes.

Carbohydrate Intake and Insulin Release

• Digestive enzymes in the gut breakdown Polysaccharides and Disaccharides releasing absorbable Monosaccharides
• When blood glucose increases it stimulates the pancreas to release insulin.
• Insulin promotes glucose uptake in the Liver, Adipose tissue and Muscle

Insulin - Responsive Tissues

• Skeletal muscle (myocytes), liver (hepatocytes), and adipose tissue (adipocytes) are the most responsive tissues to insulin.
• Insulin is an anabolic hormone.
• Insulin promotes glucose storage as proteins in muscle, carbohydrates in the liver, and lipids in adipose tissue.

Anabolic Actions of Insulin

• In the liver, insulin promotes glycogenesis and glycolysis from glucose.
• In skeletal muscle, insulin promotes glucose uptake, glycolysis, and protein synthesis from amino acids.
• In adipose tissue, insulin promotes glucose uptake, glycolysis, and lipogenesis from free fatty acids.

Glucagon Secretion

• Glucagon is stored in granules in the cytoplasm of α-cells.
• A fall in blood glucose detected by α-cells triggers glucagon secretion.
• Insulin inhibits glucagon secretion by acting on α-cells.

Glucagon Actions

• Glucagon raises blood glucose, opposing the actions of insulin.
• Glucagon is a catabolic hormone.
• Glucagon acts on glucagon G-protein-coupled receptors.

Metabolism of Glucagon

• Glucagon is metabolized by the liver (~80%) and kidneys.
• Glucagon has a half-life of about 5-6 minutes.

Catabolic Actions of Glucagon

• In the liver, glucagon promotes glycogenolysis to release glucose, gluconeogenesis from amino acids, and oxidation ultimately producing ketone bodies.
• In adipose tissue, glucagon promotes lipolysis to release free fatty acids.
• These actions are catabolic and similar to the metabolic state in diabetes.

Relationship Between Glucagon and Insulin

• In the fed state, the body absorbs nutrients, insulin dominates, resulting in net anabolism.
• Ingested glucose is used for energy production, and the excess is stored as glycogen or fat.
• Amino acids primarily go to protein synthesis.
• In the fasted state, regulation prevents low plasma glucose concentrations (hypoglycemia).
• Glucagon predominates, and the liver uses glycogen and non-glucose intermediates to synthesize glucose for release into the blood.

Diabetes Mellitus

• Diabetes Mellitus is a disorder that occurs when insulin secretion goes wrong.
• There are two types: 1 and 2.
• Main symptoms include hyperglycaemia (high blood glucose), glucosuria (glucose in the urine), polyuria (frequent urination especially at night), polydypsia (increased thirst), polyphagia (increased hunger), and tiredness.
• Treatments for Type 1 diabetes involve insulin, while Type 2 diabetes involves dietary/lifestyle management, drugs, and sometimes insulin.

Diabetes Mellitus Type 1 and Type 2

• Type 1 diabetes has a rapid onset and typically occurs before age 30, peaking at 5 or 13 years.
• Type 2 diabetes has a slow onset and typically occurs after age 40, peaking after age 60.
• Type 1 diabetes presents with weight loss, high urine output, low insulin secretion, ketosis, and >90% β-cell atrophy.
• Type 2 diabetes presents as normal/obese, with normal urine output, normal/slightly decreased insulin secretion, ketosis only on severe stress, and 30-50% β-cell atrophy.

Summary

• The endocrine pancreas anatomy is essential for understanding its function.
• Insulin lowers blood glucose and exerts anabolic effects.
• Glucagon increases blood glucose and exerts catabolic effects.
• The major disorder of the endocrine pancreas is Diabetes Mellitus.