73 - Glucose Tolerance Curves Flashcards
How does glucose enter cells?
Facilitated by GLUT transporters, SGLT in intestines.
Hydrophilic, so can’t diffuse across cell membranes.
Where is GLUT3 expressed?
In the brain
Where is GLUT4 expressed?
Muscle, adipose tissue
Km of GLUT3
Low (1.6mmol/L).
Therefore is saturated all the time (under physiological conditions)
Km of GLUT4
Medium (5mmol/l, around that of the physiological concentration of glucose in the blood)
Reason for high GLUT2 Km
GLUT2 is found in the liver.
Glucose concentration in the hepatic portal vein is significantly higher than that in general circulation, because of uptake of glucose from the gut.
High Km allows for GLUT2 to function at high glucose concentrations without saturation.
Features of GLUT transporters
1
2
3
- Uniporter specific for hexoses
- Energy-independent facilitative transport of glucose
- Glucose diffusion depends on the glucose gradient: high extracellular glucose concentration favours entry of glucose into cells via GLUT.
Fasting blood glucose physiologically
4.5-5 mmol/l
Fasting blood glucose in DM
Over 7.8mmol/l
Increase in blood glucose after a meal in a non-diabetic
4.5-6mmol/l
GLUT-mediated glucose intolerance
Aspects of DM could be also mediated by improper GLUT4 transport
Major sites of glycogen metabolism
Liver and kidney cortex
Areas of glycogen metabolism under hypoxic conditions
Astrocytes and cancer cells
Linkages between glucose monomers in glycogen
Alpha 1.4-glycosidic linkage to form strings.
Alpha-1,6-glycosidic linkage to form branches.
Rate-limiting step of glycogen breakdown
Glycogen phosphorylase.
Cleaves a glucose-1-phosphate from glycogen
Rate-limiting step in glycogen formation
Glycogen synthase.
Regulation of glycogen phosphorylase
Glucagon form the liver.
Adrenaline for muscle glycogen.
When is glucagon secreted into the blood?
When [glucose] drops below 4.5mmol/L
Glucagon receptor
GPCR.
Adenylate cyclase generates cAMP from ATP, which activates PKA.
Three precursors of gluconeogenesis
Lactate
Alanine
Glycerol
Role of Cori cycle
Converts lactate from other tissues to glucose
Roles of alanine cycle
1
2
3
Conversion of alanine from muscle to glucose.
Pyruvate can be converted to alanine.
Can transport alanine to liver for detoxification in the urea cycle.
Energy supply to skeletal muscle during rigorous activity 1 2 3 4 5
- During rigorous muscular activity, TCA cycle and electron transport chain cannot supply enough ATP because of the limitation of O2 supply.
- Derive all the ATP from glycolysis
- Inefficient: only 2 ATP/Glucose in glycolysis
- Rapid degradation of glycogen to meet the energy need
- Pyruvate conversion to lactate generates NAD+ for earlier steps in glycolysis
Function of hepatic glycolysis
Generate acetyl-CoA for fatty acid synthesis
Function of hepatic gluconeogenesis
Generate glucose to maintain blood glucose
Function of glycolysis in muscle
Generate ATP for muscle contraction
Why is muscle glycogen not depleted when glucagon is released?
Muscle cells lack glucagon receptors.
Effect of insulin on skeletal muscle
Upregulation of GLUT4
Effects of glucagon
1-4
1) Increased glycogenolysis
2) Increased gluconeogenesis
3) Reduced glycogen synthesis
4) Reduced glycolysis
Leads to the production of glucose
Effects of insulin
1-7
1) GLUT4 to membrane (in muscle and adipose tissue)
2) Glycolysis (in liver)
3) Amino acid uptake, protein synthesis (in muscle)
4) Fatty acid synthesis (in liver)
5) Glycogen synthesis (in liver and muscle)
6) Inhibits TAG breakdown (in adipose)
7) Inhibits glycogen breakdown (in liver)
