Physiology 2130 Lecture Notes - Lecture 58: Citric Acid Cycle, Glut1, Blood Sugar
Lecture 057: Glucose Homeostasis
Glucose Homeostasis - Overview
● After Eating
○ Increase in glucose, leads to:
■ Biphasic insulin response: first sharp rise in insulin, followed by a more
gradual rise in insulin
■ Decrease in glucagon
○ What to maintain glucose around 5 mmol in the blood
○ Overall objective: store extra glucose away for later
● Hypoglycemic hormone
○ Lower glucose
○ Insulin
● Hyperglycemic hormone
○ Raise glucose
○ Glucagon and stress hormone (epinephrine, cortisol)
Cellular Respiration refresher
● Glucose is the best source for the generation of cellular ATP
○ ATPis the molecule that provide energy for all cellular process
● Energy is stored in the third phosphate bond of ATP
○ Most activities in the cell are regulated by phosphorylation
● Glucose is broken down in 3 separate consecutive process
○ Glycolysis
■ Converts glucose (C6) to pyruvate or lactate (C3)
■ Produce 2 ATP
○ TCA cycle
■ Acetyl coenzyme A
■ Produce 2 ATP
○ ETC
■ Mitochondrial membrane
■ 34 STP
○ Total: 38 ATP/glucose molecule
Glucose Transporters
Name
Tissue Distribution
Important Features
GLUT1
● Brain
● Erythrocytes
● Placenta
● Fetal tissue
○ Important role in
development
Low Km (1 mM, high affinity)
● About 1 mM
● Allows for constant uptake of
glucose needed in the brain
GLUT2
● Liver
High Km (15 - 20 mM)
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● Kidney
● Intestine
● Pancreatic beta-cell
● Doesn’t need as much
glucose in these metabolic
organs because they are
constantly near glucose
anyway
● Glucose equilibrium across
membrane
GLUT3
● Only in the brain
Low Km (< 1 mM)
● Extra adaptation for the brain
in cases of hypoglycemia to
allow for preferential uptake
GLUT4
● Muscle
● Adipose
Medium Km (2.5 - 5 mM)
● Insulin sensitive receptors
○ Moves from the
cytosol to the
membrane under the
control of insulin
binding
GLUT5
● Jejunum
Medium Km (6 mM)
● Fructose uptake
● Have different binding affinity and are distributed in different organs
The Pancreas
● Acinar cells
○ Exocrine cells
○ 96%
● Islets of Langerhans
○ Endocrine
○ 4%
○ ɑ-cells
■ Produce glucagon
■ Periphery
○ β-cells
■ Produce Insulin and amyloid (misfolded insulin, toxic to β-cells)
■ Majority of the Islets of Langerhans are β-cells
○ δ-cells
■ Produce somatostatin
○ D1 cells
■ Produce VIP
○ PP cells
■ Produce pancreatic polypeptide
Insulin Biosynthesis
● Insulin is a peptide hormone produced first as a precursor then modified
● Preproinsulin
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Document Summary
Biphasic insulin response: first sharp rise in insulin, followed by a more gradual rise in insulin. What to maintain glucose around 5 mmol in the blood. Overall objective: store extra glucose away for later. Glucose is the best source for the generation of cellular atp. Atpis the molecule that provide energy for all cellular process. Energy is stored in the third phosphate bond of atp. Most activities in the cell are regulated by phosphorylation. Glucose is broken down in 3 separate consecutive process. Converts glucose (c6) to pyruvate or lactate (c3) Allows for constant uptake of glucose needed in the brain. Doesn"t need as much glucose in these metabolic organs because they are constantly near glucose anyway. Extra adaptation for the brain in cases of hypoglycemia to allow for preferential uptake. Moves from the cytosol to the membrane under the control of insulin binding. Have different binding affinity and are distributed in different organs.