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