The Feed-Fast Cycle: Role of Hormones Flashcards
Objectives: i.Explain metabolic homeostasis and describe the mechanisms involved in the inter-tissue integration required for metabolic homeostasis ii.Differentiate between the postprandial phase, the post-absorptive phase and the early phase of starvation. iii.Explain the special role of glucose in metabolic homeostasis iv.Describe in general the pathways leading to fatty acid synthesis and cholesterol synthesis in the fed state starting with glucose v.Describe the roles of insulin and glu
What hormones are the main hormonal regulators of blood glucose levels?
Insulin
Glucagon
Epinephrine
Cortisol
The _______buffers blood glucose levels. After a meal, it takes up large amounts of glucose and during fasting, it releases glucose into the blood. ________ is used in both processes.
Liver
GLUT-2
The brain uses which glut transporter for he uptake of glucose?
GLUT-1
What is postprandial?
The time of about 2-3 hours after a meal is referred to as postprandial
In the postprandial phase, the dietary monosaccharides are taken up in large amounts into the __________ via the __________. The free glucose is ________by _________and the glycogen store is filled and ______is performed. Both pathways are favored by the high ________ ratio
Liver (Glut-2) Portal Vein phosphorylated glucokinase glycolysis insulin/glucagon
At very high glucose levels and extensive glycolysis, the liver synthesizes _______ and ________.
Fatty acids
Cholesterol
The postabsorptive phase is about ____ hours after food intake.
5-7
Blood glucose levels are ______ in the postabsorptive phase
decreased
What is characteristic about the postabsorptive phase?
- high glucagon/insulin ratio
- liver releases glucose
- Insulin = low
- Epinephrine & Cortisol = elevated; leading to lypolysis
What processes are favored by high glucagon/insulin ratio?
Glycogen degradation
Gluconeogenesis
How do hepatocytes release free glucose into the blood?
GLUT-2
The liver glycogen stores are empty after about______ and from then on, _________ will provide the blood glucose that is needed for the total body.
1 day
gluceneogensis
How does ACTH released under stress situations affect Insulin?
Under stress situations, the pituitary gland releases ACTH which stimulates release of cortisol from the adrenal cortex
- Cortisol leads in the adrenal medulla to methylation of norepinephrine to epinephrine (PNMT, SAM) and release of both catecholamines into the blood
- Epinephrine inhibits insulin release from b-cells and stimulates glucagon release from a-cells
Cortisol has no effect on ________ but stimulates _________
Glycogen breakdown
Gluconeogenesis
Epinephrine/Norepinephrine stimulates _______ but has no effect on ________
Glycogen breakdown
Gluconeogenesis
Glucagon stimulates both _____ and _____
Glycogen breakdown
Gluconeogensis
Glucagon leads in the liver to ______ and to _____.
Degradation of fatty acids
Synthesis of ketone bodies
Cortisol supports gluconeogensis by inducing what enzyme needed for long term gluconeogenesis?
PEP carboxykinase
Insulin release is favored by glucose and what amino acids?
especially by Leucine (dietary essential)
also arginine
Glucagon release is favored by epinephrine and what amino acids?
Especially alanine
also arginine
Which amino acid leads to the release of both insulin and glucagon?
Arginine
Gluconeogensis is only performed where?
Liver
Ketogenesis is only performed where?
Liver
High levels of glucose after a meal lead in the liver to? In fat cells to? In muscle to?
Liver: Glycolysis, glycogen synthesis, fatty acid and cholesterol synthesis
Fat cells: Glycolysis and TAG synthesis
Muscle: Glycolysis and glycogen synthesis
High levels of blood fatty acids during fasting lead in the liver to? In the muscle to?
Liver: B-oxidation of FA and Ketogenesis
Muscle: B-oxidation
Insulin induces key enzymes of irreversible steps of
Glycolysis
PPP
FA and cholesterol synthesis
Glucagon induces key enzyme of irreversible steps of
Gluconeogenesis
What are the key regulated enzymes of lipid metabolism in the liver (the enzymes are induced by insulin)
FA (de novo) synthesis:
- Acetyl CoA Carboxylase
- FA synthase complex
Cholesterol synthesis:
-HMG CoA reductase
What are the key regulated enzymes of lipid metabolism in fat cells?
TAG Degradation:
- Hormone-sensitive lipase (inactive at insulin ruling; need P for activation)
Fat cells after a meal: high insulin blood levels mobilize ______ in fat cells and activates ______ in capillaries.
GLUT-4
Lipoprotein Lipase
Why is the blood glucose level critical and well regulated?
Blood glucose is the primary fuel for the brain in the well-fed state and also during the first days of fasting. Glucose is also all the time the only fuel for RBC and other cells without mitochondria
Which key regulatory enzymes of glycolysis and the PPP are active in the liver at high serum insulin/glucagon ratio?
Insulin induces the key regulatory enzymes of liver glycolysis and the PPP: glucokinase, PFK-1, the bifunctional enzyme, pyruvate kinase and glucose 6-P dehydrogenase.
The PFK-2 activity of the bifunctional enzyme and pyruvate kinase are dephosphorylated and active. The PPP is active as the demand for NADPH is increased during synthesis of fatty acids and cholesterol.
How is it regulated that glycolysis and not gluconeogenesis takes place in liver at high insulin/ratio?
At insulin/glucagon ratio, the bifunctional enzyme forms fructose 2,6-bisphosphate which has two allosteric actions: a.) it activates PFK-1 ( which is the key regulated enzyme of glycolysis) and b.) at the same time, other molecules of fructose 2,6-bisphosphate inhibit fructose 1,6-bisphosphatase (the key regulated enzyme of gluconeogenesis) in the liver
How is it regulated that glycogen synthesis and not glycogen degradation takes place in the liver at high insulin/glucagon ratio?
Insulin leads to the active (dephosphorylated) glycogen synthase.
Insulin leads to the inactive (dephosphorylated) glycogen phosphorylase kinase which results in the inactive (dephosphorylated) glycogen phosphorylase
