Factors that stimulates and inhibits insulin secretion
Stimulators :
1- Glucose
2- Gastrin , Secretin , CCK
3- β – ketoacids
4- Acetylcholine
5- β – Adrenergic stimulators
6- Theophylline
7- Sulfonylureas
Inhibitors :
1- Somatostatin
2- Epinephrine and nonepinephrine
3- Propranolol which is used for treatment of blood pressure
4- K ion depletion
5- Phenytoin
Glucagon
Glucagon has a major role in maintaining normal concentration of glucose in
blood and is often described as having the opposite effect of insulin. That is,
glucagon has the effect of increasing blood glucose levels.
Glucagon is linear peptide of 29 amino acids which is synthesized as
proglucagon and proteolytic processed to yield glucagon within alpha cells
of pancreatic islet.
Effect of glucagon on glucose metabolism
The major effect of glucagon on glucose metabolism are :
1- Breakdown of liver glycogen (Glycogenolysis)
2- Increase gluconeogenesis in the liver (Formation of sugar form amino
acids)
Both of those effects enhance the availability of glucose to other organs of
the body.
Other effects of glucagon occur only when its concentration rises well above
the maximum normally found in blood. The most important effect is that
glucagon activates adipose cell lipase, making increased quantities of fatty
acids. Also inhibits the storage of triglycerides in the liver which prevents
the liver form removing fatty acids from blood.
Glucagon in very high concentration also:
1- Enhances the strength of the heart.
2- Increases blood flow in some tissues.
3- Enhances bile secretion.
4- Inhibits gastric acid secretion.
Control of glucagon secretion:
Knowing that glucagon’s major effect is to increase blood glucose levels, it
makes sense that glucagon is secreted in response to hypoglycemia or low
blood concentration of glucose.
Two other conditions are known to trigger glucagon secretion:
Elevated blood of amino acids as would be seen after consumption of
a protein-rich meal, in this situation glucagon would accelerate
conversion of excess amino acid to glucose by enhancing
gluconeogenesis. Since high blood levels of amino acids also
stimulate insulin release, this would be a situation in which both
insulin and glucagon are active.
Exercise : in this case, it is not clear whether the actual stimulus is
exercise per se, or the accompanying exercise-induced depletion of
glucose.
In terms of negative control, glucagon’s secretion is inhibited by high levels
of blood glucose. It is not clear whether this reflects a direct effect of
glucose on the alpha cells or perhaps an effect of insulin which is known to
dampen glucagon release.
Another hormone well known to inhibit glucagon secretion is somatostatin.
Somatostatin inhibits glucagon and insulin secretion
The delta cells of the islet of hangerhans secrete somatostatin which is a
polypeptide containing 14 amino acid, it has short half life of 3 minutes.
Almost all factors related to the ingestion of food stimulates somatostatin
secretion, they include:
1- Increased blood glucose.
2- Increased amino acids.
3- Increased fatty acids.
4- Increased concentration of several GIT hormones.
In turn somatostatin has multiple inhibitory effect:
1- Somatostatin acts locally within the islets of langerhans themselves to
decrease the secretion of both insulin and glucagon.
2- Somatostatin decreases the motility of the stomach, duodenum and
gall bladder.
3- Somatostatin decreases both secretion and absorption in GIT.
The principle role is to extend the period of time over which the food
nutrients are assimilated into the blood.
Somatostatin
At the same time the effect of somatostatin to depress insulin and glucagon
secretion decreases the utilization of the absorbed nutrients by the tissues,
thus preventing rapid exhaustion of the food and making it available over a
longer period of time.
Somatostatin is the same chemical substance as growth hormone inhibitory
hormone which is secreted in the hypothalamus and suppresses anterior
pituitary gland growth hormone secretion.
Diabetes mellitus
Is the syndrome of impaired carbohydrate, fat and protein metabolism
caused bt wither lack of insulin secretion or decreased sensitivity of the
tissues to insulin. There are two types of diabetes mellitus:
1- Type 1 ((IDDM)) (Insulin dependent diabetes mellitus) caused by lack
of insulin secretion.
2- Type 2 ((NIDDM)) (Non insulin dependent diabetes mellitus) caused
by decreased sensitivity of target tissues to the metabolic effect of
insulin.
In both types of diabetes, metabolism of all the food stuffs is altered. The
basic effect of insulin lack or insulin resistance on glucose metabolism is to
prevent the efficiency uptake and utilization of glucose by most cells of the
body and those of the brain.