Pancreas is composed of two major types of tissues.
1. The Acini: which secrete digestive juices into the duodenum.
2. The islets of Langerhans: Contain three major types of cells INSULINMetabolized by the enzyme Insulinase (present mainly in the liver, kidneys and muscles).
Insulin is a small protein, it is composed of two amino acid chains connected to each otherby disulfide linkages. When the two amino acid chainsare split apart, the functional activity of the insulinmolecule is lost.
Insulin is synthesized in the beta cells.
Diabetes Mellitus
2. PANCREAS
Pancreas is composed of two
major types of tissues.
1. The Acini: which secrete
digestive juices into the
duodenum.
2. The islets of Langerhans:
Contain three major types of cells
1) Alpha cells (25%) → glucagon
2) Beta cells (60%)→ Insulin
3) Delta cells (10%) →
Somatostatin
4) Pancreatic Acini (small
amount) → Pancreatic
Polypeptide
3.
4. INSULIN
Metabolized by the enzyme
Insulinase (present mainly in the
liver, kidneys and muscles).
Insulin is a small protein, it is
composed of two amino acid
chains connected to each other
by disulfide linkages. When the
two amino acid chains
are split apart, the functional
activity of the insulin
molecule is lost.
Insulin is synthesized in the beta
cells.
It is first synthesized by ribosomes
attached to the E.R to form an
Preproinsulin. It is then cleaved in
the endoplasmic reticulum to form
a proinsulin with a molecular
weight
of about 9000; most of this is
further cleaved in the
Golgi apparatus to form insulin
and C peptide. However, about
one sixth of the final secreted
product
is still in the form of proinsulin.
The proinsulin and C peptide has
virtually no insulin activity.
7. INSULIN RECEPTOR
The insulin receptor is a
combination of four subunits held
together by disulfide linkages:
Two alpha
subunits that lie entirely outside the
cell membrane
and two beta subunits that penetrate
through the cell membrane.
The insulin binds with the alpha
subunits on the outside of the cell
become autophosphorylated.
Thus, the insulin receptor is an
example of an enzyme-linked
receptor, Autophosphorylation of
the beta
subunits of the receptor activates
a local tyrosine
Insulin binds to its receptor &
activates tyrosine kinase, causes
phosphorylation of different
enzymes, which in turn leads to
the action of Insulin. Beta cells
have large number of glucose
transporters (GLUT 2) that
permit glucose influx.
9. ACTIONS OF INSULIN
EFFECT ON CARBOHYDRATES
Catabolic
Insulin Promotes Muscle Glucose Uptake.
In case of excess glucose causes storage of glucose in form of muscle
glycogen.
Insulin Promotes Liver glucose Uptake and storage in the liver by:
Insulin inactivates liver phosphorylase that causes liver glycogen to split
into glucose.
increasing the activity of the enzyme glucokinase, causes enhanced
uptake of glucose from the blood by the liver cells.
Insulin increases the activities glycogen synthase causes increase
glycogen synthesis.
10. Glucose Is Released from the Liver Between Meals when glucose
level is low and lack of insulin.by:
It activates the enzyme phosphorylase, which causes the splitting of
glycogen into glucose phosphate.
The enzyme glucose phosphatase, activated by the
insulin lack and causes the phosphate radical to
split away from the glucose; this allows the free
glucose to diffuse back into the blood.
11. • Insulin Promotes Conversion of Excess Glucose into Fatty Acids
and Inhibits Gluconeogenesis in the Liver .
• The brain is quite different from other tissues of body. The brain cells are
permeable to
glucose and can use glucose without the intermediation
of insulin.
• Effect on fat Metabolism
Anabolic effect
Insulin promotes fat synthesis
Insulin decreases the utilization of fat(Fat sparer).
Insulin promote fat storage in the adipose cells by inhibits the action of. of
hormone-sensitive
lipase. That causes hydrolysis of
the triglycerides already stored in the fat cells
12. Effect on Protein Metabolism
Anabolic
Insulin Promotes Protein Synthesis and Storage.
It increases uptake of A.A by the cells.
It inhibits protein catabolism.
When there is lack of Insulin, proteins in the body are depleted
Insulin and GH interact synergistically to
promote growth.
13. Deficiency of Insulin causes:
Insulin Deficiency Causes Lipolysis of Storage Fat by activating enzyme
“hormone-sensitive lipase and Release
of Free Fatty Acids.
Insulin Deficiency Increases Plasma Cholesterol and Phospholipid
Concentrations.
Lack of insulin causes Excess Usage of Fats Causes Ketosis because lack
of Insulin causes formation of acetoacetic acid in the liver. some of the
acetoacetic
acid is also converted into b-hydroxybutyric acid and
acetone. And causes severe acidosis and coma .
causes fat utilization for energy everywhere except in the brain
14.
15. Diabetes Mellitus
Diabetes mellitus is a syndrome of impaired
carbohydrate, fat, and protein metabolism caused by
either lack of insulin secretion or decreased sensitivity
of the tissues to insulin.
16. Types of Diabetes Mellitus
Type I diabetes, also called insulin dependent diabetes
mellitus (IDDM), is caused by lack of insulin secretion.
Type II diabetes, also called non–insulin-dependent
diabetes mellitus (NIDDM), is caused by decreased
sensitivity of target tissues to the metabolic effect of
insulin. This reduced sensitivity to insulin is often called
insulin resistance
19. Type 1 Diabetes Mellitus
(Juvenile Diabetes)
Etiology:
• Injury to the beta cells of
the pancreas
• diseases that impair
insulin production
• Viral infections or
autoimmune disorders
• hereditary
Features
1.Increased blood glucose
2.Increased utilization of fats
for energy and for formation
of cholesterol by the liver
3.Depletion of the body’s
proteins
20. 1. Increased Blood
Glucose
(Hyperglycemia)
Causes
Loss of Glucose in the
Urine.
Dehydration
Chronic condition Causes
Tissue Injury
Blood Vessel injury
Peripheral Neuropathy
Hypertension
Atherosclerosis
2. Increased utilization of fats
Causes
Excessive release of keto acids
Ketosis
increased deposition of cholesterol
3. Depletion of Body Proteins
Decreased storage of proteins
rapid weight loss and asthenia
(lack of energy) despite eating large
amounts of food (polyphagia)
Acetone Breath
More common in type I diabetes.
Acetoacetic acid is converted in
acetone. This is volatile and
vaporized in to expired air.
21. Sign & Symptoms
Hyperglycemia
Glycosuria
Acidosis
ketosis.
Polydypsia
Polyphagia
Polyuria
Acidosis
Normal blood glucose
level in fasting is
100mg/dl.
In D.M, blood glucose
level is even more than
400mg/dl.
Normal levels of
ketoacids in blood:
1m Eq
In D.M: 30 mEq
22. Type II Diabetes Mellitus
Type II diabetes is more common than
type I, accounting for about 90 per
cent of all cases of diabetes mellitus
In most cases, the onset of type II
diabetes occurs after age 30, often
between the ages of 50 and 60 years,
and the disease develops gradually.
This syndrome is often referred to as
adult-onset diabetes.
Causes
Obesity
Insulin Resistance ( increased plasma
insulin cpncentration causes decrease
activity of target tissues)
“Metabolic Syndrome” Usually
Precede Development of Type II
Diabetes.
Metabolic Syndrome:
Obesity especially accumulation of
abdominal fat
Insulin resistance
Fasting hyperglycemia
Lipid abnormalities such as
increased blood triglycerides and
decreased blood high-density
lipoprotein cholesterol
Hypertension
23. Diagnosis of Diabetes
Urinary Glucose
Fasting blood Glucose Levels : a person with
diabetes has fasting blood glucose level is always
above 110 or above 140 mg /100ml.
Glucose Tolerance Test
HbA1c
C-Peptide
Urinary Ketone Bodies