glucose metabolism

Biochemical-Clinical Analysis Module

  • Complementary Module: Dietary Techniques (6 CFU)

  • Integrated Exam: Human Nutrition Applied (12 CFU)

Lecture and Teaching Materials

  • Provided by Prof. Curcio.

  • Key texts may include:

    • Henry's Clinical Diagnosis and Management by Laboratory Methods by Richard A. McPherson & Matthew R. Pincus (Elsevier)

    • Clinical Biochemistry: Metabolic and Clinical Aspects by William J. Marshall et al. (Elsevier)

  • Contact: rositacurcio@yahoo.it

Glucose Homeostasis

  • Plasma glucose concentration is influenced by:

    • Absorption from the gastrointestinal tract

    • Use at the tissue level

    • Endogenous production

  • In fasting conditions, a 70 kg person uses about 200g of glucose per day (2mg/kg/min).

  • Key Hormones:

    • Insulin and insulin-like growth factors

    • Counteracting hormones (e.g., glucagon, catecholamines, GH, cortisol)

Metabolic Utilization of Glucose

  • Red blood cells and brain cells utilize approximately 80% of dietary glucose.

  • Blood glucose levels must be replenished; hypoglycemia occurs if levels fall below 2.5 mmol/l.

  • Intestinal Absorption: Glucose absorption primarily occurs 2-3 hours post carbohydrate meal.

Pancreatic Hormones

  • Endocrine Pancreas:

    • Produces hormones: Insulin, Glucagon, Somatostatin

  • Exocrine Function:

    • Produces digestive enzymes (zymogens activated in the duodenum).

GLUT Family of Transporters

  • Transport Mechanism: Glucose is transported via GLUT proteins (membrane transporter superfamily - MFS).

  • Classes of GLUTs:

    • Class I: GLUT1-4 and 14 (primarily glucose transporters)

    • Class II: GLUT5, 7, 9, 11 (transport various molecules)

    • Class III: GLUT6, 8, 10, 12, 13 (transport other molecules)

GLUT1

  • Expression: Highly expressed in erythrocytes, brain, muscle, adipose tissue.

  • Km Value: ~2 mM (lower than blood glucose concentration).

  • Role: Crucial for glucose transport to the brain and other tissues; increased expression during low blood glucose levels.

GLUT2

  • Expression: High in the liver, pancreatic β-cells, intestine, renal cells.

  • Functions: Transports glucose (Km = 20 mM) and fructose, not saturated in hepatocytes.

  • Facilitates fructose removal from portal circulation and glucose reabsorption in kidneys.

GLUT3

  • Main Role: Primarily in the brain; functions swiftly to transport glucose across the blood-brain barrier.

  • Km Value: ~1-2 mM; vital for neuronal and embryonic glucose supply.

GLUT4

  • Expression: Insulin-sensitive tissues (heart, skeletal muscle, adipose).

  • Km Value: 2-5 mM, similar to fasting blood glucose concentrations.

  • Regulation Mechanisms:

    • Post-translational modifications (glycosylation, phosphorylation)

    • Protein turnover (transcription/degradation)

    • Membrane translocation influenced by insulin.

GLUT5

  • Function: Higher affinity for fructose, primarily expressed in the small intestine and kidneys.

  • Regulation: Upregulated in type 2 diabetes within skeletal muscle and intestines.

Glycogen Metabolism in the Liver

  • Key Functions:

    • Efficient glucose uptake via GLUT2, where it's phosphorylated into glucose-6P.

    • Liver acts as a glucose buffer through gluconeogenesis, glycogen synthesis and conversion of other sugars.

Regulation of Blood Glucose

  • Hormonal Control: Insulin stimulates glucose uptake in muscles and liver, promotes glycogen synthesis.

  • Counter-Hormones: Glucagon induces gluconeogenesis, mobilizes glycogen, inhibits glycolysis.

Metabolism During Fasting

  • Hepatic Glycogenolysis: Active during fasting, releasing glucose into the bloodstream.

  • Cori Cycle: Lactate and alanine from muscle convert back into glucose in the liver.

Ketone Bodies

  • Production: Excess fatty acid breakdown results in ketone body formation (acetoacetate, acetone, B-hydroxybutyrate).

  • Metabolic Impact: Lowers blood pH; brain can utilize ketone bodies for energy during prolonged fasting.

Insulin Mechanism of Action

  • Synthesis: Produced in β-cells of the pancreas; increases glucose uptake and ATP production.

  • Deficiency Effects: Causes insulin-dependent diabetes mellitus (IDDM), leading to a failure of glucose uptake.

Summary of Insulin Actions

  • Effects on Blood Glucose: Promotes glucose uptake in muscles and liver, enhances glycogen synthesis, and fatty acid synthesis.

  • Opposite Effects of Glucagon: Increases blood glucose via mobilization of glycogen and stimulation of gluconeogenesis.