Metabolic effects of insulin & glucagon. ENDO412. Introduction. Fuels are biomolecules (as carbohydrates, lipids & proteins) that can yield energy in the form of ATP on (catabolism or degradation). This energy (ATP) that can be used for all biological processes of the cells.
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Fuels are biomolecules (as carbohydrates, lipids & proteins) that can yield
energy in the form of ATP on (catabolism or degradation). This energy (ATP) that can
be used for all biological processes of the cells.
Fuels can be also stored in certain sites of the body in the form of larger molecules
(anabolism or building) to be released in case of demand.
These procedures (catabolism & anabolism) are called energy metabolism.
Energy metabolism occurs mainly in 4 organs; liver, adipose, muscles & brain, in
which energy is stored, produced & released according to needs of the body.
These 4 organs communicate in a way that one of them produces substrates for another.
Among these 4 organs, energy metabolism is integrated & regulated primarily by the action of insulin & glucagon
(with catecholamines plays a supporting role).
In case of well-fed state (directly after ingestion of a meal):
There is a abundance of energy yielding fuels (glucose etc..) more than actual body needs for energy.
Excess of fuels (energy) is stored by help of INSULIN hormone.
In case of stress or prolonged fasting (post absorptive):
These is a lack in energy-yielding fuels to give sufficient energy to all body.
Stored fuels are released to be available for used by cells of the body by the help
of GLUCAGON hormone.
Also, epinephrine plays a role in this status.
Generally, insulin hormone is:
Insulin + C-peptide
Insulin & C-peptide are stored in cytosol as granules
To be released by certain stimulus by exocytosis to blood
C-peptide has a longer half-life in the plasma more than insulin.
& hence is a good indicator of insulin production & secretion in early cases of DM
Insulin is required for storing of glucose in liver.
Glucagon is required for releasing glucose from its stores in liver.
So, both hormones secretion from pancreas has to be regulated according to needs of the body.
1-Factors stimulating of insulin secretion:
- Glucoseingestion (or carbohydrate rich meals)
- Amino Acids
- Gastrointestinal hormones (as cystokinines & gastric-inhibitory polypeptides) increase
insulin secretion in response to oral glucose
2-Factors inhibiting insulin secretion:
Decrease of synthesis of insulin occurs when there is a scarcity of diet fuel & during periods of stress.
These effects are mediated by epinephrine, which causes rapid mobilization of energy-yielding fuels (including glucose from liver & fatty acids from adipose tissue).
Epinephrine binds to a-adrenergic receptors on b-cells resulting in decrease of insulin secretion.
Promotes storage of glucose
Glycogen Glycogen uptake of
Synthesis Synthesis glucose
Gluconeogenesis Intake of
Entry of AA into cells
Of Insulin on a-cells
Gene Metabolism Growth
Glucose transport in some
tissues as skeletal muscles
& adipocytes increase in
the presence of insulin
Insulin promotes the
recruitment of insulin-sensitive
glucose transporters (GLUT-4)
from a pool located in
N.B. Some tissues do not depend on insulin for glucose transport
As Liver cells, RBCs, neurons, intestinal mucosa, renal tubules & cornea
Binding of insulin to its receptors on various cells provoke a
wide range of actions that varies in time course.
Some may occur immediately within few seconds, while others need
Immediate(within seconds): increased glucose transport into adipose tissue & sk. ms.
Within minutes to hours: changes in activity of enzymes.
(phosphorylation of proteins i.e. enzymes)
Within hours to days: increase amounts of many enzymes
(increase in gene expression with increase in mRNA & enzyme synth.)
Binding of insulin to its receptors is followed by internalization of hormone-
Once inside cells, insulin is degraded in lysosomes.
Receptors are either degraded or recycled to cell surface.
Elevated levels of insulin promote the degradation of receptors, with a decrease in
the number of surface receptors (a type of down regulation)
a-cells are responsive to a variety of stimuli that signal hypoglycemia (actual or about to occur)
Glucagon secretion is increased by:
1- Low blood glucose in blood:
During an overnight or prolonged fasting, elevated glucagon levels prevent hypoglycemia.
2- Amino acids:
Amino acids released from meals containing protein stimulate both glucagon & insulin.
In this case, glucagon prevents the hypoglycemia that would occur as a result of increased insulin
secretion after a protein meal.
Epinephrine is released either by adrenal medulla or by sympathetic innervations of pancreas or both)
in cases of stress, trauma or severe exercise.
In these cases, glucagon levels are elevated to be ready for the possibility of increased glucose use.
Glucagon secretion is significantly decreased by :
- Elevated blood glucose
Both substances are increased following ingestion of glucose or
Increases blood glucose
in adipose tissue
Uptake of AA by liver
Carbon skeleton for gluconeogenesis