Blood Glucose Regulation: Insulin and Glucagon

Blood Glucose Regulation

• Two hormones regulate blood glucose: insulin and glucagon
• Glucose (C6H12O6) is a monosaccharide and the fuel for making ATP in cellular respiration
• Glycogen is a polysaccharide and a form of energy storage
• Insulin and glucagon have antagonistic effects and work together to maintain blood sugar homeostasis

Insulin vs. Glucagon

• Insulin is released by β-cells in the pancreas and helps glucose enter cells, decreasing blood glucose levels
• Glucagon is released by α-cells in the pancreas and stimulates the liver to increase blood glucose levels
• Insulin acts as a key to facilitate glucose transport into cells, while glucagon promotes glycogen breakdown to glucose

Control of Blood Glucose Levels

• High blood sugar:
  • Stimulates pancreatic insulin release
  • Insulin facilitates glucose transport, glycogen synthesis, and inhibits glycogenolysis, lipolysis, and gluconeogenesis
• Low blood sugar:
  • Stimulates pancreatic glucagon release
  • Glucagon promotes glycogen breakdown, gluconeogenesis, and inhibits protein synthesis

Insulin and Oral Hypoglycaemic Agents

• Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels
• Two main types of diabetes:
  • Type I (Insulin-Dependent Diabetes Mellitus): autoimmune or idiopathic, with low insulin levels
  • Type II (Non-Insulin-Dependent Diabetes Mellitus): high insulin levels, insulin resistance, and late onset

Insulin Mechanism of Action

• Insulin acts on specific receptors on the cell membrane, which are receptor tyrosine kinases
• Insulin binding causes a conformational change, activating the tyrosine kinase activity, which stimulates glucose uptake, glycogen synthesis, and inhibits glycogenolysis

Insulin Preparations

• Four types of insulin preparations:
  • Rapid-acting (lispro, aspart, glulisine): peak effect 1-1.5 hours, duration 3-4 hours
  • Short-acting (regular insulin): peak effect 2.5 hours, duration 4-6 hours
  • Intermediate-acting (NPH or isophane insulin): peak effect 8 hours, duration 10-16 hours
  • Long-acting (insulin detemir, insulin degludec, insulin glargine): no peak effect, duration 24 hours

Adverse Effects of Insulin

• Hypoglycaemia, lipodystrophy, redness, swelling, itching, weight gain, sweating, coma, fatigue, hunger

Oral Hypoglycaemic Agents

• Biguanides (metformin, phenformin):
  • Mechanism of action: inhibits hepatic gluconeogenesis, increases glycolysis, and peripheral glucose uptake
  • Adverse effects: lactic acidosis, B12 deficiency, gastrointestinal upset
• Sulphonylureas (first, second, and third generation):
  • Mechanism of action: insulin secretagogues, blocking ATP-dependent K+ channel, sensitizing β-cells to glucose, and limiting gluconeogenesis
  • Adverse effects: hypoglycaemia, weight gain, stomach upset, hunger
• Meglitinides (nateglinide, repaglinide):
  • Mechanism of action: increases insulin release, blocking ATP-dependent K+ channel
  • Adverse effects: hypoglycaemia
• DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, vildagliptin):
  • Mechanism of action: inhibits DPP-4, potentiating GLP-1
  • Adverse effects: stomach upset, upper respiratory infection, stuffy or runny nose, headache
• GLP-1 agonists (dulaglutide, semaglutide, exenatide, liraglutide):
  • Mechanism of action: stimulates glucose-dependent insulin release, inhibits glucagon release, and slows gastric emptying
  • Adverse effects: pancreatitis, diarrhoea, headache, weakness, dizziness
• SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin):
  • Mechanism of action: inhibits sodium-glucose cotransporter-2, decreasing glucose reabsorption
  • Adverse effects: glucosuria, urinary tract infection, vaginal yeast infection, hyperkalaemia, dehydration, ketoacidosis
• Alpha-glucosidase inhibitors (acarbose, miglitol):
  • Mechanism of action: inhibits intestinal brush-border alpha-glucosidases, converting complex carbohydrates to monosaccharides
  • Adverse effects: gastrointestinal distress, increased colonic gas production
• Thiazolidinediones (glitazones):
  • Mechanism of action: activates PPARs, increasing insulin sensitivity
  • Adverse effects: heart failure, weight gain, macula edema, increased fracture risk
• Amylin:
  • Mechanism of action: inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent
  • Adverse effects: nausea, vomiting, headache, hypoglycaemia

Learn how insulin and glucagon hormones regulate blood glucose levels, and understand the difference between glucose and glycogen. Discover how these hormones work together to maintain energy balance.