Download regulation of blood glucose dr abdelaziz

‫بسم هللا الرحمن الرحيم‬
‫﴿و ما أوتيتم من العلم إال قليال﴾‬
‫صدق هللا العظيم‬
‫االسراء اية ‪58‬‬
Regulation of Blood
Glucose
By
Dr. Abdel Aziz M. Hussein
Lecturer of Physiology
Member of American Society of Physiology
• The normal blood glucose level ranges ( ) 80-120
mg %.
• The total amount of glucose in circulating blood is
about 3.3 to 7gm
• 5 grams of glucose is about equivalent to a
commercial sugar packet (as provided in many
restaurants with coffee or tea).
• Failure to maintain blood glucose in the normal
range leads to conditions of persistently high
(hyperglycemia) or low (hypoglycemia) blood
sugar.
•
Normal Blood glucose is regulated by 2 mechanisms:
A. Hormones
Pancreatic hormones
e.g. insulin, glucagon, and
somatostatin
Other hormones e.g.
adrenaline, thyroxin,
glucocorticoids, and
Growth hormone
B. Tissues
Liver acts as
glucostat
• Liver maintains normal
blood glucose level
(glucose buffer function)
by;
1. Glycogenesis
(breakdown of glycogen
into glucose)
2. Glycogenolysis
(formation of glycogen
from glucose)
3. Gluconeogenesis
(formation of glucose
from non carbohydrates
fats and proteins)
• Endocrine cells of the pancreas are present in groups
called ‘islets of Langerhan’s’
• Are more numerous in the tail than in the body
• Islets are 1-2% of its pancreatic weight
Alpha cells
25 %
Secretes
Glucagon
Beta cells
60%
Secretes
Insulin
Delta cells
10%
Secretes
somatostatin
F cells
5%
Secretes
pancreatic
polypeptide
Chemistry :
• Insulin is secreted from beta cells of islets of Langerhans
• Insulin is one of the most important peptide hormones.
• It consists of 2 straight chains linked by 2 disulfide bridges.
1. A chain → contains 21 amino acids and an intra-chain
disulfide ring.
2. B chain → contains 30 amino acids.
Mechanism of action:
• Insulin acts on insulin receptor (2 subunits, alpha and beta
subunits).
• It is a tyrosine kinase i.e. functions as an enzyme that
transfers phosphate groups from ATP to tyrosine residues on
intracellular target proteins.
• Binding of insulin to the alpha subunits causes the beta
subunits to phosphorylate themselves
(autophosphorylation), thus activating the catalytic activity
of the receptor.
• The activated receptor then phosphorylates a number of
intracellular proteins called insulin-receptor substrates
(IRS1-4).
• These substrates are coupled to several additional protein
kinase signal systems
CHO and fat metabolism
Insulin tends to lower blood glucose level i.e.
hypoglycemic hormone, by:
1. Increase glucose uptake by the tissues (liver, ms, and
fat tissues) by insertion of GLUT4 into cell membrane
2. Stimulate glycogenesis in Liver and SK. Ms
3. Inhibition of glycogenolysis
4. Inhibition of gluconeogenesis
5. Stimulate lipogenesis in adipose tissue
N.B.
• Insulin stimulate glucose entry in all tissues except brain
cells, RBCs, intestinal cells and renal tubule cells
Insulin Action in Muscle and Fat Cells
Mobilization of GLUT4 to the Cell Surface
Plasma membrane
Insulin
receptor
Intracellular
signaling
cascades
Intracellular
GLUT4 vesicles
Insulin
GLUT4 vesicle mobilization
to plasma membrane
GLUT4 vesicle
integration into
plasma membrane
GLUT4=glucose transporter 4
Glucose
Glucose entry into cell
via GLUT4 vesicle
Protein and Mineral Metabolism
Insulin is powerful anabolic hormone and stimulate tissue
growth by :
1. Stimulates the uptake of certain amino acids by Sk. Ms
2. Stimulates the rate of protein synthesis (enhance
activity of ribosomes)
3. Anticatabolic effects i.e. inhibits proteolysis.
4. Insulin increases cellular uptake of potassium, phosphate
and magnesium
Stimuli of Insulin Secretion
1. Blood glucose:
• Virtually, no insulin is secreted below a plasma glucose level of 50
mg%.
• A half maximum insulin secretory response occurs at a plasma
glucose level of about 150 mg%
• A maximum response at 300 to 500 mg%.
2. GIT hormones:
a. Gastric inhibitory polypeptide (GIP):
• The most important of insulinogogue i.e. stimulate insulin secretion
b. High concentrations gastrin, secretin, cholecystokinin, pancreatic
glucagons and enteroglucagon stimulate insulin secretion
3. ↑ Blood free fatty acids, ketoacids and triglycerides
have little effect
4. ↑ blood amino acids e.g. arginine, leucine, lysine and
alanine
Stimuli of Insulin Secretion
5. Other hormones e.g. Glucagon, GH, cortisol
6. Parasympathetic (Ach) and Beta adrenergic stimulation.
7. Obesity
8. Sulfonylurea drugs
Inhibitors of Insulin Secretion
1.
2.
3.
4.
5.
6.
Fasting
Exercise
Somatostatin
-Adrenergic stimuli
Prostaglandins
Drugs e.g. Diazoxide and Phenytoin
Chemistry :
• Polypeptide hormone (29 amino acid)
• Secreted by  cells of the pancreatic islets.
Functions :
1. On CHO metabolism:
• It increases blood glucose i.e. hyperglycemic
hormone by:
a) It stimulate glycogenolysis
b) It stimulates gluconeogenesis
2. It stimulates lipolysis
4. It inhibits renal tubular Na reabsorption.
5. It stimulates cardiac contractility
Functions :
2. Glucagon activates adipose tissue lipase→ lipolysis→
delivery of free fatty acids from adipose tissue to the liver
and ketogenesis.
3. It decreases hepatic cholesterol synthesis.
4. Natriuresis, by inhibition of renal tubular Na reabsorption.
5. Activation of myocardial adenyl cyclase, causing a
moderate increase of cardiac output.
6. May act as a local CNS hormone for the regulation of
appetite.
1. Adrenaline: glycogenolytic acting on both liver and
muscles.
2. Glucocorticoids: Stimulate gluconeogenesis and
depress glucose uptake by the tissues.
3. Growth hormone: Stimulates the release of
glucagon hormone and also inhibits glucose uptake
by tissues.
4. Thyroxin: It increases glucose absorption from the
intestine, glycogenolysis and glucose uptake by cells.
The net result is a rise in blood glucose level.
• Maintenance of blood glucose constant is important
because;
• glucose is the only nutrient used by the brain, retina and
germinal epithelium of the gonads
• Too high blood glucose level produce many harmful effects
such as;
1. Glucose can exert a large amount of osmotic pressure in
the ECF that leads to cellular dehydration
2. Loss of glucose in urine
3. Osmotic diuresis by the kidneys
4. Long-term increases in blood glucose may cause damage
to many tissues especially to blood vessels→ ↑es risk for
heart attacks and cerebral strokes.
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