• Two adrenal glands
• Each weighs 4 grams
• Lie at the superior poles of the two kidneys
• Two distinct parts, adrenal medulla and adrenal
Adrenal medulla, central 20 % of the gland, is
functionally related to the sympathetic nervous
• It secretes epinephrine and norepinephrine in
response to sympathetic stimulation
Adrenal cortex secretes corticosteroids.
Androgens (small amounts)
• Mineralocorticoids: affect electrolytes (“minerals”)
of extracellular ﬂuids -sodium and potassium, in
• Glucocorticoids : important effects that increase
blood glucose concentration + additional effects on
protein and fat metabolism
• More than 30 steroids have been isolated from the
• Aldosterone principal mineralocorticoid
• Cortisol principal glucocorticoid.
• Three Distinct Layers
1. Zona glomerulosa, 15% of the adrenal cortex
• A thin layer of cells that lies just underneath the
• Secrete aldosterone
• Secretion is controlled by ECF concentrations of
angiotensin II and potassium, which stimulate
2. Zona fasciculata, 75% of the adrenal cortex
• Middle and widest layer
• Secretes glucocorticoids cortisol, corticosterone, and
small amounts of adrenal androgens and estrogens.
• Secretion is controlled by the hypothalamic-pituitary
axis via adrenocorticotropic hormone (ACTH).
• Zona reticularis, deep layer of cortex
• Secretes adrenal androgens,
dehydroepiandrosterone (DHEA) and
androstenedione, small amounts of estrogens
• ACTH regulates secretion of these cells
• Cortical androgen-stimulating hormone,
released from the pituitary, may also be
Adrenocortical Hormones Are Steroids
• Derived from Cholesterol
• Cholesterol is provided by LDL in the circulating
• Transport of cholesterol is regulated by feedback
• For example, ACTH increases the number of
adrenocortical cell receptors for LDL, as well as the
activity of enzymes that liberate cholesterol from LDL.
• Cholesterol enters cell, delivered to mitochondria,
cleaved by enzyme cholesterol desmolase to form
• This initial step in steroid synthesis is stimulated by
the different factors that control secretion of the
Synthesis of Adrenal Steroids
• Synthesis occur in two of the organelles of the
cell, mitochondria and endoplasmic reticulum
• Each step is catalyzed by a speciﬁc enzyme
MSc Essex University March 2010
Adrenal Steroids and Pathways
MSc Essex University March 2010
Enzymes in Steroid Biosynthesis
• Side-chain cleavage enzyme; desmolase
• 3 beta-hydroxysteroid dehydrogenase (3 beta HSD)
• 17 alpha-hydroxylase.
• 21-hydroxylase .
• 11 beta-hydroxylase .
• 18 hydroxylase (aldosterone synthase .
• 17 beta-hydroxysteroid dehydrogenase
• Aromatase .
• Mutation or failure of any of these genes can lead endocrine
More Important Glucocorticoid Hormones including
- Aldosterone (very potent, accounts for 90% of all
- Desoxycorticosterone (1/30 as potent as aldosterone, but very
small quantities secreted
- Corticosterone (slight minralocorticoid activity)
- 9a-Fluococortisol (synthetic, slightly more potent than
- Cortisol (very slight mineralocorticoid activity, but large
- Cortisone (synthetic, slight mineralocorticoid activity)
- Cortisol (very potent, accounts for about 95% of all
- Corticosterone (provides 4% of total glucocorticoid) activity,
much less potent than cortisol)
- Cortisone (synthetic, almost as potent as cortisol)
- Prednisone (synthetic, four times as potent as cortisol)
- Methyprednisone (synthetic, five tmes as potent as cortisol)
- Dexamethasone (synthetic, 30 times as potent as cortisol)
The Intense Glucocorticoid Activity of Dexamethasone,
has almost zero mineralocorticoid activity, thus is
important drug for stimulating specific glucocorticoid
Biochemical actions of adrenocorticosteroids
A. Mineralocorticoids: aldosterone
It promotes Na+ reabsorption at the distal convoluted tubules of
kidney. Na+ retention is accompanied by corresponding excretion
of K+,H+ and NH4
1. Effects on glucose metabolism: They promote gluconeogenesis.
They work in tandem with insulin from the pancreas to maintain
blood glucose levels in the proper balance.
2. Effects on lipid metabolism: They increase lipolysis in adipose
tissue and reduce synthesis of triglyceride
3. Effects on protein and nucleic acid metabolism: They promote
transcription and protein synthesis in liver. They also cause catabolic
effects in extrahepatic tissues results in enhanced degradation of
B. Glucocorticoids: Cortisol
4. Effects on water and electrolyte metabolism: Deficiency of them
cause increased production of ADH which can decrease glomerular
filtration rate causing water retention in the body.
5. Effects on immune system: Cortisol suppress the immune response
directly and indirectly by affecting most cells that participate in immune
reactions and inflammatory reactions. It is powerful anti-inflammatory
even when secreted at normal levels. This is one of the reasons why
strong corticosteroids (prednisone, prednisolone, etc.) are used with all
diseases involving inflammatory processes, including auto-immune
6. Effects on cardiovascular system: Cortisol could control the
contraction of the walls of the mid-sized arteries in increasing blood
pressure, but this hypertensive effect is moderated by calcium and
magnesium. It also directly affects the heart by regulating sodium and
potassium in the heart cells and increasing the strength of contraction of
the heart muscle.
7. Effects on central nervous system: The changes of behavior, mood,
excitability and even the electrical activity of neurons in the brain
frequently occur in cases of excess and deficient cortisol levels. Many
signs and symptoms of adrenal fatigue involve moodiness, decreased
tolerance, decreased clarity of thought and decreased memory. These
occur because the brain is affected by both too little and too much
Adrenal Medullary Hormones
•Cells in the adrenal medulla synthesize and secrete
epinephrine and norepinephrine.
•The ratio of these two catecholamines
differs considerably among species:
in humans, roughly 80, of the catecholamine output is epinephrine.
•Following release into blood, these hormones bind adrenergic
receptors on target cells, where they induce essentially the same
effects as direct sympathetic nervous stimulation
Synthesis and Secretion of Catecholamines
Synthesis of catecholamines begins with the amino acid tyrosine, which is taken
up by chromaffin cells in the medulla and converted to norepinephrine and
epinephrine through the following steps:
Norepinephine and epinephrine are stored in electron-dense granules which also
contain ATP and several neuropeptides.
Secretion of these hormones is stimulated by acetylcholine release from preganglionic
sympathetic fibers innervating the medulla.
Many types of "stresses" stimulate such secretion, including exercise, hypoglycemia
and trauma. Following secretion into blood, the catecholamines bind loosely to and
are carried in the circulation by albumin and perhaps other serum proteins.
Complex physiologic responses result from adrenal medullary stimulation because
there are multiple receptor types which are differentially expressed in different
tissues and cells.
The alpha and beta adrenergic receptors and their subtypes were
originally defined by differential binding of various agonists and antagnonists and,
more recently, by analysis of molecular clones.
Effects of Medullary Hormones
In general, circulating epinephrine and norepinephrine released from the
adrenal medulla have the same effects on target organs as direct stimulation
by sympathetic nerves, although their effect is longer lasting.
•Increased rate and force of contraction of the heart muscle:
•this is predominantly an effect of epinephrine acting through beta receptors.
•Constriction of blood vessels: norepinephrine, in particular, causes widespread
vasoconstriction, resulting in increased resistance and hence arterial blood pressure.
•Dilation of bronchioles: assists in pulmonary ventilation
•Stimulation of lipolysis in fat cells: this provides fatty acids for energy production
in many tissues and aids in conservation of declining reserves of blood glucose.
•Increased metabolic rate: oxygen consumption and heat
production increase throughout the body in response to
• Medullary hormones also promote breakdown of glycogen
in skeletal muscle to provide glucose for energy production.
•Dilation of the pupils.
•Inhibition of certain "non-essential" processes: an example is
inhibition of gastrointestinal secretion and motor activity.
Common stimuli for secretion of adrenomedullary hormones
include exercise,hypoglycemia, hemorrhage and emotional
Regulation of glucocorticoids
The Secretion of glucocorticoids from the adrenal cortex is regulated
by negative feedback involving the CRH secretion by the hypothalamus.
CRH then acts on the anterior pituitary to stimulate ACTH secretion,
which then stimulates the adrenal cortex into cortisol secretion. About
70% of blood cortisol is bound to a carrier protein called corticosteroid-
binding globulin. Another 15% is bound to albumin, the remaining 15%
exists free in solution.
The HPA axis or HPA system, a negative
feedback system, is one of the most
important elements of homeostasis, the
process that maintains a steady internal
biochemical and physiological balance in
your body. The HPAAxis adjusts cortisol
level according to the needs of the body,
under normal and stressed conditions, via
ACTH. ACTH is secreted from the pituitary
gland in response to orders form the
hypothalamus and travels in the
bloodstream to the adrenal cortex.
※ The Hypothalamus/Pituitary/Adrenal (HPA) Axis
Stress: During stress cortisol must
simultaneously provide more blood glucose,
mobilize fats and proteins for a back-up
supply of glucose, modify immune reactions,
heartbeat, blood pressure, brain alertness and
nervous system responsiveness. If cortisol
level cannot rise in response to these needs,
maintaining your body under stress is nearly
Renin-angiotensin-aldosterone (control system)
•Renin, a proteolytic enzyme, secreted by juxtaglomerular cells (JG) of the
juxtaglomerular apparatus (JGA)
•Baroreceptors and chemoreceptors of JGA are sensitive to:
- hypovolemia renin
- concentration of Na renin
•The renin-angiotensin system is also stimulated by:
- sympathetic nervous system renin
•Aldosterone secretion is controlled by: ECF volume BP or Na
renin (JGA) angiotensin (plasma) angiotensin I
angiotensin II aldosterone (zona glomerulosa) *“converting enzyme”
converts ANG I to ANG II]
• K adrenal zona glomerulosa aldosterone
MSc Essex University March 2010
Adrenal gland disorders
• Disorder of adrenal cortex
1-Adrenal Insufficiency (Hypoadrenalism)
Congenital adrenal hyperplasia (CAH)
2--Adrenal over production(Hyperadrenalism)
• Cushing’s syndrome
• Conn’s syndrome
• Disorder of adrenal medulla
Adrenal Insufficiency (AI)
• Impairment in synthesis and/or release of
• Classified as:
– Primary AI results from disease intrinsic to
the adrenal cortex
– Secondary AI results from impaired release or
effect of adrenocorticotropic hormone (ACTH)
from the pituitary gland
– Tertiary AI results from the impaired release
or effect of corticotropin releasing hormone
(CRH) from the hypothalamus
is adrenocortical insufficiency due to the
destruction or dysfunction of the entire
adrenal cortex. It affects both
glucocorticoid and mineralocorticoid
function. The onset of disease usually
occurs when 90% or more of both adrenal
cortices are dysfunctional or destroyed.
• Failure of the adrenal cortices to produce adrenocortical
• Most frequently caused by primary atrophy of the
adrenal cortices, caused by autoimmunity against the
• Also caused by tuberculous destruction of the adrenal
glands or invasion of the adrenal cortices by cancer.
• These processes usually are gradual, leading to a
progressive reduction in glucocorticoid and
• As a result of the decreased cortisol secretion, there is a
compensatory increase in ACTH secretion, which
• Mineralocorticoid Deficiency
• Excessive loss of sodium, hypovolemia, hypotension,
and increased plasma renin activity
• Excessive potassium retention and hyperkalemia
• Mild acidosis
• Glucocorticoid Deficiency
• Abnormal carbohydrate, fat, and protein metabolism
resulting in muscle weakness, fasting hypoglycemia, and
impaired utilization of fats for energy
• Loss of appetite and weight loss
• Poor tolerance to stress.
• The inability to secrete increased amounts of cortisol
during stress leads to an Addisonian crisis that may end
in death if supplemental doses of adrenocortical
hormones are not administered.
Acute adrenal (addisonian) crisis
• Clinical features – fever, dehydration,
nausea, vomiting, hypotension, that evolves
rapidly to circulatory shock.
• The onset of symptoms most often is insidious and
• Hyperpigmentation of the skin and mucous
membranes vitiligo:Dizziness , Myalgias and flaccid
muscle paralysis may progressive weakness, fatigue,
poor appetite, and weight loss.
• gastrointestinal symptoms may include nausea,
vomiting, and occasional diarrhea.
Laboratory Investigations …
• Synacthen stimulation test
– Measuring levels of cortisol in blood before and 30 and 60
minutes after an injection of 250µg synthetic ACTH
• If the adrenal glands are functional - cortisol levels will
rise in response to the ACTH stimulation If they are
damaged or non-functional - response to ACTH will be
• ACTH - baseline test to evaluate whether or not the pituitary
is producing appropriate amounts of ACTH.
– low ACTH levels indicate secondary adrenal insufficiency
– high levels indicate primary adrenal insufficiency
• Congenital adrenal hyperplasia (CAH)
• is a group of inherited autosomal-recessive
disorders in which a genetic defect results in the
deficiency of an enzyme essential for synthesis of
cortisol and, at times, aldosterone. There are
several forms of CAH, the most common of which
is 21-hydroxylase (21-OH) deficiency, occurring in
over 90% of all cases
Some autosomal recessive mutations in biosynthetic enzymes
responsible for converting cholesterol to androgens generally lead to
partial male-to-female sex reversal.
CAH is a deficiency of 21-hydroxylase enzyme ( most common)
causing a decrease in synthesis of steroid hormones,leading to
overproduction of ACTH. When this occurs adrenal steroid synthesis is
stimulated and 17-hydroxyprogesterone is converted to androstenedione
and further to testosterone, leading to severe virilization of the female
fetus. This disorder is known as CAH which disrupts the synthesis of all
adrenal and gonadal steroids. Affected genetic males are born with
normal female external genitalia.
congenital adrenal hyperplasia CAH :
Presentations of CAH
• Ambiguous genitalia in girls
• Salt-loss presentations with electrolytes imbalance
• Hypersecretion by the adrenal cortex causes a complex
cascade of hormone effects called Cushing’s syndrome.
• Hypercortisolism can occur from multiple causes:
1) adenomas of the anterior pituitary ACTH
adrenal hyperplasia cortisol secretion
2) abnormal function of the hypothalamus CRH
3) “ectopic secretion” of ACTH by a tumor in the body
4) adenomas of the adrenal cortex
5) by administration of large amounts of exogenous
• When Cushing’s syndrome is secondary to excess
secretion of ACTH by the anterior pituitary, this is
referred to as Cushing’s disease.
• Cushing’s syndrome is caused by prolonged
exposure of the bodies’ tissue to high levels of
the hormone cortisol
• Cushing syndrome is also called hypercortisolism.
• Upper body obesity (moon face, increased
neck fat buffalo hump)
• Thinning around the arms and legs
• Delayed growth
• Easy bruising of skin
• Purplish-pink stretch marks on the abdomen,
thigh, buttocks, arms, and breasts
• High blood sugar, high blood pressure
• Depression and anxiety
• Increased hair growth in women
• Irregular menstrual cycles
• Bones are fragile, susceptible to fractures
• Characterized by excessive secretion of aldosterone from the
• Also referred to as primary hyperaldosteronism
• Excessive aldosterone is produced by One or more benign
• Commonly occurs in adults between the ages of 30 and 50
(although it can be in anyone)
• Most common cause of secondary hypertension
• More common in women than men
• Presence of hypokalemia with hypertension - suggests
possible primary hyperaldosteronism.
Primary Aldosteronism or Conn’s
• Excessive aldosterone secondary to adrenal tumor
• retain sodium and excrete potassium
• Results in alkalosis
• Hypertension—universal sign of hyperaldosteronism
• Inability of kidneys to concentrate the urine
• Serum becomes concentrated
• Excessive thirst
• Hypokalemia interferes with insulin secretion thus will
have glucose intolerance as well
a neuroendocrine tumor of the medulla of the adrenal glands
(originating in the chromaffin cells), or extra-adrenal chromaffin
tissue that failed to involute after birth and secretes excessive
amounts of catecholamines, usually adrenaline (epinephrine) if
in the adrenal gland and not extra-adrenal, and noradrenaline
• Usually benign tumor
• Originates from the chromaffin cells of the adrenal medulla
• Any age but usually. Between 40-50 years old
• Can be familial
• May be associated with thyroid carcinoma or parathyroid
hyperplasia or tumor
• Headache, diaphoresis, palpitations, hypertension
• May have hyperglycemia related to excess epinephrine
• Tremors, flushing and anxiety as well
• Blurring of vision
• Feeling of impending doom
• BPs exceeding 250/150 have occurred
• Digestive functions
• Secretes two important hormones
Secretes other hormones, such as amylin,
somatostatin, and pancreatic polypeptide
Physiologic Anatomy of the Pancreas
Two major types of tissues
1) The acini,which secrete digestive juices into duodenum
2) The islets of Langerhans, which secrete insulin and glucagon
1 to 2 million islets of Langerhans, organized around small
capillaries into which its cells secrete their hormones.
The islets contain three major types of cells alpha, beta, delta cell
The beta cells 60 % of all the cells of the islets, lie mainly in the
middle of each islet and secrete insulin and amylin,
The alpha cells, 25 % of the total, secrete glucagon
The delta cells, about 10 %, secrete somatostatin.
One other type of cell, the pancreatic polypeptide PP cell, is
present in small numbers in the islets and secretes pancreatic
The endocrine cells of the pancreas are localized in the islets of
Langerhans and constitute only 2% of the mass of the pancreas. The
human pancreas contain about 1 million islets of Langerhans which
are distributed throughout the organ, but more commonly found in
Both insulin and glucagon are synthesized as large preprohormones.
• In Endoplasmic reticulum, the prohormones are formed.
• Most of this is further cleaved in the Golgi apparatus to form hormone
and peptide fragments before being packaged in the secretory granules.
In the case of the beta cells, insulin and connecting (C) peptide are
released into the circulating blood in equimolar amounts.
Insulin is a polypeptide containing two amino acid chains A and B(21 and
30 amino acids, respectively) connected by disulfide bridges.
Glucagon is a straight-chain polypeptide of 29 amino acid residues.
Both insulin and glucagon circulate unbound to carrier proteins and have
short half-lives of 6 minutes.
Approximately 50% of the insulin and glucagon in blood is metabolized in
the liver; most of the remaining hormone is metabolized by the kidneys.
Structure of Insulin
• Insulin is a polypeptide
hormone, composed of
two chains (A and B)
• Both chain are derived
from preproinsulin, then
• The two chains are joined
by disulfide bonds.
Physiologic Effects of Insulin
The Insulin Receptor (IR) and Mechanism of Action
Like the receptors for other protein hormones, the
receptor for insulin is embedded in the plasma
membrane ( PM).
The IR is composed of 2 alpha subunits and 2 beta
subunits linked by S-S bonds. The alpha chains are
entirely extracellular and house insulin binding
domains, while the linked beta chains penetrate
through the PM.
Actions of Insulin
• To initiate its effects on target cells, insulin first
binds with and activates a membrane receptor
• The insulin receptor is a tetramer made up of
two α-subunits that lie outside the cell
membrane and two β-subunits that penetrate
the cell membrane and protrude into the
• When insulin binds with the alpha subunits on
the outside of the cell, portions of the beta
subunits protruding into the cell become
Thus, the insulin receptor is an example of an enzyme-linked
Autophosphorylation of the beta subunits of the receptor
activates a local tyrosine kinase, which in turn causes
phosphorylation of multiple other intracellular enzymes
including a group called insulin-receptor substrates (IRS).
The net effect is to activate some of these enzymes while
In this way, insulin directs the intracellular metabolic machinery
to produce the desired effects on carbohydrate, fat, and protein
Insulin Is a Hormone Associated with Energy
• When there is great abundance of energy-giving foods in
the diet, especially excess amounts of carbohydrates,
insulin is secreted in great quantity.
• Insulin plays an important role in storing the excess energy.
• In the case of excess carbohydrates, it causes them to be
stored as glycogen mainly in the liver and muscles.
• Excess carbohydrates is also converted under the stimulus
of insulin into fats and stored in the adipose tissue.
• Insulin has a direct effect in promoting amino acid uptake
by cells and conversion of these amino acids into protein.
• In addition, it inhibits the breakdown of the proteins that
are already in the cells.
Specific Targets of Insulin Action:
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate carboxykinase.
Increased activity of glucose transporters.
Moves glucose into cells.
Specific Targets of Insulin Action: Lipids
Activation of acetyl CoA carboxylase. Stimulates
production of free fatty acids from acetyl CoA.
Activation of lipoprotein lipase (increases
breakdown of triacylglycerol in the circulation).
Fatty acids are then taken up by adipocytes, and
triacylglycerol is made and stored in the cell.
Role of Insulin in Storage of Fat in the Adipose
• Insulin has two other essential effects that are
required for fat storage in adipose cells:
1. Insulin inhibits the action of hormone-sensitive
lipase. This is the enzyme that causes hydrolysis of
the triglycerides already stored in the fat cells.
2. Insulin promotes glucose transport through the cell
membrane into the fat cells. Some of this glucose is
then used to synthesize minute amounts of fatty
acids, but forms large quantities of a-glycerol
phosphate. This substance supplies the glycerol that
combines with fatty acids to form the triglycerides
that are the storage form of fat
Effect of Insulin on Protein Metabolism and on Growth
• Insulin Promotes Protein Synthesis and Storage
• During the few hours after a meal proteins are also
stored in the tissues by insulin
1. Insulin stimulates transport of many of amino acids
into the cells, eg valine, leucine, isoleucine, tyrosine,
2. Insulin increases the translation of mRNA, thus
forming new proteins
3. Over a longer period of time, insulin also increases
the rate of transcription of selected DNA, forming
increased quantities of RNA and still more protein
4. Insulin inhibits the catabolism of proteins
5. In the liver, insulin depresses the rate of gluconeogenesis,
this suppression of gluconeogenesis conserves the amino
acids in the protein stores of the body.
• In summary, insulin promotes protein formation and
prevents the degradation of proteins
• Lack of Insulin causes protein depletion and increased
plasma amino acids
• The resulting protein wasting is one of the most serious of
all the effects of severe diabetes mellitus.
• It can lead to extreme weakness as well as many deranged
functions -of the organs.
Insulin and Growth Hormone Interact
Synergistically to Promote Growth
• Because insulin is required for the synthesis of
proteins, it is as essential for growth as growth
• A combination of these hormones causes
• Thus, it appears that the two hormones
function synergistically to promote growth each
performing a specific function that is separate
from that of the other.
•Glucagon is a catabolic peptide hormone secreted by α cells of the pancreatic islets
Regulation of secretion
•Glucagon secretion is directly stimulated by:
- low blood glucose concentration
- high levels of circulating amino acids
•Somatostatin glucagon secretion
•Insulin & secretin glucagon secretion
•Sympathetic stimulation glucagon secretion (ß-receptor mechanism)
•Vagal stimulation glucagon secretion
•All forms of physical stress glucagon secretion
Targets of Glucagon Action
• Activates a phosphorylase, which cleaves off a
glucose 1-phosphate molecule off of glycogen.
• Inactivates glycogen synthase by phosphorylation
(less glycogen synthesis).
• Increases phosphoenolpyruvate carboxykinase,
• Activates lipases, breaking down triglycerides.
• Inhibits acetyl CoA carboxylase, decreasing free fatty
acid formation from acetyl CoA
• Result: more production of glucose and substrates for
Glucagon Action on Cells: Dominates in Fasting
A few hours after a meal (active):
- blood glucose levels decrease
- insulin secretion decreases
- increased secretion of glucagon, cortisol, GH,
- glucose is released from glycogen stores
- increased lipolysis (beta oxidation)
- glucose production from amino acids
increases (oxidative deamination;
- decreased uptake of glucose by tissues
- blood glucose levels maintained
Hormonal Regulation of Nutrients
•Somatostatin is a peptide hormone secreted by δ cells of the
pancreatic islets (also produced in the hypothalamus) in response to:
- blood glucose
- plasma amino acids
- fatty acids
•Somatostatin decreases gastrointestinal functions by:
•Somatostatin release of:
• 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
• Two forms of diabetes mellitus
• Type I diabetes mellitus, also called insulin-
dependent diabetes mellitus (IDDM), is caused by
impaired secretion of insulin.
• Type II diabetes mellitus, also called non–insulin-
dependent diabetes mellitus (NIDDM), is caused by
resistance to the metabolic effects of insulin in
Type I Diabetes
• Caused by Impaired Secretion of Insulin by the Beta Cells
of the Pancreas
• Often, type I diabetes is a result of autoimmune
destruction of beta cells, but it can also arise from the loss
of beta cells resulting from viral infections.
• Because the usual onset of type I diabetes occurs during
childhood, it is referred to as juvenile diabetes.
• Pathophysiological features:
• Hyperglycemia as a result of impaired glucose uptake into
tissues and increased glucose production by the liver
• Depletion of proteins resulting from decreased
synthesis and increased catabolism
• Depletion of fat stores and increased ketosis
• As a result of these fundamental derangements:
• Glucosuria, osmotic diuresis, hypovolemia
• Hyperosmolality of the blood, dehydration,
• Hyperphagia but weight loss; lack of energy
• Acidosis progressing to diabetic coma; rapid and
• Hypercholesterolemia and atherosclerotic vascular
Type II Diabetes Mellitus
• Insulin Resistance Is the Hallmark of Type II Diabetes
• Type II diabetes is far more common than type I
diabetes (accounting for approximately 90% of all
cases of diabetes)
• Usually associated with obesity.
• This form of diabetes is characterized by impaired
ability of target tissues to respond to the metabolic
effects of insulin, which is referred to as insulin
• In contrast to type I diabetes, pancreatic beta cell
morphology is normal throughout much of the
disease, and there is an elevated rate of insulin
• Type II diabetes usually develops in adults and
therefore is also called adult-onset diabetes.
• Caloric restriction and weight reduction usually
improve insulin resistance in target tissues
• Drugs that increase insulin sensitivity, such as
metformin, or drugs that cause additional release
of insulin by the pancreas, such as sulfonylureas,
may also be used.
• In the late stages of the disease when insulin
secretion is impaired, insulin administration is
Glucose Tolerance Test
•when a normal, fasting person
ingests 1 gram
of glucose per kg of body
weight, the blood
glucose level rises from about
90 mg/100 ml to 120 to
140 mg/100 ml and falls back to
below normal in
about 2 hours.
•In a person with diabetes, this
test is always abnormal