Diabetes, Insulin, and Glucagon Notes

Diabetes, Insulin, and Glucagon

Insulin and Glucagon Overview

  • Insulin and Glucagon are two hormones produced by the pancreas.

Insulin - Fed State (Storing Energy)

  • Insulin is associated with the fed state, focusing on storing energy (sugars and fatty acids) for later use.
  • Increases glucose entry into cells
  • Increases glycogen formation: Glycogen is the storage form of glucose.
    • Endurance athletes tend to have lower glycogen levels.
    • Sprinters typically have high glycogen levels for short bursts of energy.
  • Decreases lipolysis: Inhibits the breakdown of fats.
  • Increases fatty acid storage
  • Increases protein synthesis
  • Decreases gluconeogenesis: Reduces glucose formation in the liver.

Hypoglycemia (Low Blood Sugar)

  • Hypoglycemia is the condition of having low blood sugar.
  • Some drugs can cause hypoglycemia, including:
    • Ethanol
    • ACE inhibitors
    • Beta blockers
    • Lithium

Hyperglycemia (High Blood Sugar)

  • Hyperglycemia is the condition of having high blood sugar.
  • Some drugs can cause hyperglycemia, including:
    • Epinephrine
    • T3 (Triiodothyronine, a thyroid hormone)
    • Thyroxine (a thyroid hormone)
    • Growth hormone
    • Cortisol
    • Corticosteroids
    • NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
    • Diuretics

Glucagon - Starve State (Releasing Sugar)

  • Glucagon is associated with the starved state, triggering the release of sugar (not fats) into the blood.

Diabetes Type 1

  • Insulin-dependent
  • Signs and Symptoms:
    • Hyperglycemia: High blood sugar.
    • Fasting glucose + 160
    • Polyuria: Excessive urination.
    • Polyphagia: Excess hunger.
    • Polydipsia: Excess thirst.
    • Glucose in the urine (Glucosuria)
    • Glucosuria has a prevalence of 1/100,000 people.
    • Weight loss
    • Fatigue
  • Pathophysiology: No insulin production by the body, necessitating insulin administration.
  • Diagnostic Criteria:
    • HIAC (Glycosylated hemoglobin) > 6.5
      • Treatment goal is to keep it below 6.5.
    • Fasting oral glucose < 126 after 8 hours
    • Oral glucose tolerance test ? 200Mg/ld
  • Treatment:
    • Insulin (both slow-acting and fast-acting formulations)

Diabetes Type 2

  • Insulin-independent
  • Insulin resistance: The body produces insulin, but it is not as effective at the cell level.
  • Precursor: Metabolic syndrome, which leads to a pre-diabetic state.
  • Treatments (Drug Classes):
    • Sulfonylureas (Oral medication)
      • Examples:
        • Glyburide (DiaBeta)
      • Mechanism:
        • Increase insulin secretion by the pancreas.
        • Increase the sensitivity of insulin receptors to insulin.
      • Side Effects:
        • Hypoglycemia (low blood sugar)
    • Biguanides
      • Example:
        • Metformin (Glucophage)
      • Mechanism:
        • Decrease gluconeogenesis by the liver.
        • Decrease insulin resistance.
      • Does not alter pancreatic insulin secretion.
      • Can decrease glucose in Type 1 patients.
      • Major use is in treating Type 2 diabetes.
      • Decreases triacylglycerols.
      • Decrease LDL via a decrease in VLDL secretion
    • Thiazolidinediones (TZDs)
      • Example:
        • Pioglitazone (Actos)
      • Mechanism:
        • Stimulate PPAR Alpha and PPAR Gamma, which control lipid synthesis and gluconeogenesis.
      • Effects:
        • Decrease in liver glucose secretion.
        • Increase in insulin sensitivity.
    • Incretin inhibitor
      • Example:
        • Tanzeum (Albiglutide)
      • Mechanism:
        • Stimulate GLP1 (glucagon-like peptide 1).
      • Effects:
        • Very expensive.
        • Increase creatine.
        • Stimulates fullness.
        • Increase pancreas insulin secretion.
        • Decrease glucagon.

Diabetic Ketoacidosis (DKA)

  • Excessive use of lipids for energy.
  • The liver shifts to making ketone bodies.
  • Decrease blood PH – that is the acidosis part