Glucagon and Blood Glucose Regulation

Glucagon

• Glucagon is a polypeptide hormone secreted by the α-cells of the pancreatic islets of Langerhans.
• Glucagon, in conjunction with epinephrine, cortisol, and growth hormone, acts primarily to maintain blood glucose levels.
• Glucagon achieves this by activating hepatic glycogenolysis (breakdown of glycogen) and gluconeogenesis (formation of glucose from non-carbohydrate sources).
• Glucagon secretion is stimulated by low blood glucose and amino acids.
• It is inhibited by elevated blood glucose and insulin.

Metabolic Effects of Glucagon

• Glucagon leads to an immediate rise in blood glucose levels.
• It activates lipolysis (breakdown of fat) in adipose tissue.
• Free fatty acids released are used for ketone body synthesis in the liver.
• Glucagon increases the uptake of amino acids by the liver, promoting gluconeogenesis.

Other Hormones Regulating Blood Glucose

• Epinephrine: synthesized by the adrenal medulla, released in response to hypoglycemia.
  • Stimulates glycogenolysis and gluconeogenesis in the liver.
  • Inhibits insulin release.
• Cortisol: glucocorticoid hormone produced by the adrenal cortex.
  • Extended elevations lead to hyperglycemia.
  • Increases gluconeogenesis and antagonizes insulin action.
• Growth Hormone (Somatotropin): produced by the anterior pituitary gland.
  • Prolonged elevations result in hyperglycemia.
  • Stimulates gluconeogenesis, enhances lipolysis, and antagonizes insulin function.
• Thyroxine: secreted by the thyroid gland.
  • Plays a minor role in direct glucose regulation.
  • Can promote glycogenolysis and deplete liver glycogen.
  • May increase glucose absorption.

Alterations in Carbohydrate Metabolism

• Hyperglycemia is more prevalent than hypoglycemia.
• Normal fasting plasma glucose range is between 70-110 mg/dl.
• Non-fasting glucose range for individuals is between 70-150 mg/dl.

Diabetes Mellitus

• A group of metabolic diseases characterized by hyperglycemia.
• Caused by defects in insulin secretion, insulin action, or both.
• Categorized into four main types:
  • Type 1 diabetes
  • Type 2 diabetes
  • Other specific types of diabetes
  • Gestational diabetes mellitus (GDM)

Type 1 Diabetes Mellitus (Insulin-dependent diabetes mellitus)

• Characterized by destruction of beta cells in the pancreas, leading to an absolute insulin deficiency.
• Often diagnosed in childhood and adolescence.
• Requires insulin therapy.
• Subtypes:
  • Autoimmune induced
  • Idiopathic diabetes mellitus
  • Latent autoimmune diabetes of adults (LADA)

Type 2 Diabetes Mellitus (T2DM)

• Most common type of diabetes.
• Characterized by insulin resistance at target tissues.
• Typically acquired after age 40, but can occur in younger individuals.
• Genetic factors play a role in the development of T2DM.
• Environmental factors, such as diet and obesity, are also influential.
• Often managed through dietary changes and weight loss.
• Insulin therapy may be needed in some cases.

Pathogenesis of Type 2 Diabetes

• Insulin Resistance:
  • Decreased biological response to normal levels of insulin.
  • Found in obese non-diabetic individuals and in patients with type 2 diabetes.
  • Can be associated with the "insulin resistance syndrome" or "metabolic syndrome," which includes:
    • Insulin resistance
    • Hyperinsulinemia
    • Obesity
    • Dyslipidemia (high triglycerides and low HDL cholesterol)
    • Hypertension
• Metabolic Syndrome:
  • Diagnosed when an individual meets three or more of the following criteria:
    • Abdominal obesity (waist circumference > 35 inches (women) or 40 inches (men))
    • Triglycerides > 150 mg/dl
    • HDL cholesterol < 50 mg/dl (women) or < 40 mg/dl (men)
    • Blood pressure ≥ 130/85 mm Hg
    • Fasting plasma glucose ≥ 110 mg/dl
  • Increases the risk of cardiovascular disease.
• Loss of Beta Cells:
  • Increased β cell demand due to insulin resistance is associated with a progressive loss of β cell function.
  • This loss contributes to the development of fasting hyperglycemia.
  • Characterized by a loss of glucose-induced insulin release, termed "selective glucose unresponsiveness."
• Environmental Factors:
  • Diet and exercise are important contributors to the development of type 2 diabetes.
  • All obese individuals, even those with normal carbohydrate tolerance, have hyperinsulinemia and insulin resistance.
  • Family history, duration of obesity, and fat distribution are also important factors.

Comparing Type 1 and Type 2 Diabetes

This quiz covers the role of glucagon in blood glucose regulation, including its metabolic effects and interactions with other hormones such as epinephrine. Explore how glucagon stimulates glycogen breakdown and gluconeogenesis, and its response to varying blood glucose levels.