Endocronology.ppt for Nurse students

1. 1
Endocrine physiology

2. Endocrinology
• Is the study of hormones derived from the
classical endocrine glands or from other cells or
tissues such as the brain or GI tract.
2

3. • Activities of cells, tissues, and organs of the body are coordinated by
several types of chemical messenger systems:
– Hormones are delivered from the cell of origin to their target cells by
one of several routes.
– Endocrine hormones
– Neurotransmitters
– Neuroendocrine hormones
– Paracrines
– Autocrines
3

4. 4
Chemical classification of Hormones
• There are three general classes of hormones:
• 1. Proteins and polypeptides, including hormones secreted by:
– Anterior and posterior pituitary gland
– Pancreas (insulin and glucagon)
– Parathyroid gland (parathyroid hormone) & many others
In general Peptides Hormones are :-

5. • 2. Steroids secreted by:
– Adrenal cortex (cortisol and aldosterone)
– Ovaries (estrogen and progesterone)
– Testes (testosterone)
– Placenta (estrogen and progesterone)
5

6. 3. Derivatives of the amino acid tyrosine
secreted by
– Thyroid (thyroxine and triiodothyronine)
– Adrenal medullae (epinephrine and
norepinephrine)
– Pineal gland (Melatonin)
• Are derived from tyrosine and
tryptophan.
6

7. Mechanisms of Action of Hormones
The physiological processes regulated by hormones result
from interaction of the hormone with receptors.
Charactersics of Hormone-Receptor Interaction
• 1. Specficity
• 2. Saturation
• 3. Competition
Where does hormone –receptor interaction occur
at the target cell ????????????
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• The first step of a hormone's action is to bind to specific receptors at
the target cell.
– Cells that lack receptors for the hormones do not respond.
The locations for the different types of hormone receptors are:
1. In or on the surface of the cell membrane.
– Such receptors are specific mostly for the protein, peptide, and
catecholamine hormones.
– Act through 20 messengers
– 20 messengers Can be:
• cAMP
• cGMP
• TK
• IP3
• Ca++

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• 2. In the cell, either:
• A. In the cell cytoplasm
– The primary receptors for the different steroid hormones are found mainly in
the cytoplasm.
• B. In the nucleus.
– The receptors for the thyroid hormones
– believed to be located in direct association with one or more of the chromosomes.
Such receptor hormones are
lipid soluble,
readily cross cell membrane

• interact with receptors in
the cytoplasm or nucleus

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These proteins then function as
enzymes, transport proteins, or
structural proteins,
which in turn provide other
functions of the cells.

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• Endocrine basis of hormone disorders:
1. Over production
2. Under production
3. Non-functional receptors or Hormone resistancy

• target cells become insensitive to the hormone.
4. Autoimmune syndrome caused by
autoantibodies directed against cell-
surface receptors. Myasthenia gravis
5. Diseases associated with continuously
activated receptors can mimic a state
of hormone excess

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• Endocrine glands: divided in to two; central &
peripheral
A. Central endocrine glands- include;
– Hypothalamus
– Pituitary gland (hypophysis)
• Adenohypophysis
• Neurohypophysis - extension of hypothalamus
• Pituitary gland, (hypophysis) is a small gland
 1cm in diameter and 0.5 – 1gm weight
 lies in the sella turcica, a bony cavity at the base of
the brain,
 connected to the hypothalamus by the pituitary
(hypophysial) stalk

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• Two hormones secreted by neurohypophysis play other
roles.
– Antidiuretic hormone (also called vasopressin)
– Oxytocin
• Almost all secretion by the pituitary is controlled by either:
– hormonal signals from the hypothalamus or
– nervous signals from the hypothalamus
B. Peripheral endocrine glands- include:
– thyroid glands,
– parathyroid glands,
– thymus gland,
– pancrease,
– gonads…

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• Central endocrine glands: Hypothalamus and Pituitary
Glands
• Hypothalamus
– the main coordinating center b/n the endocrine & nervous
system
– exerts its effects on pituitary gland in two different
ways:
A. Hypothalamo neUrohypophysial axis
• Posterior Pituitary Gland / neurohypophysis
– is composed mainly of glial-like cells called pituicytes
• do not secrete hormones;
• act simply as a supporting structure for large numbers
of terminal nerve
fibers

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• B. Hypothalamo adenohypophysial axis
• Anterior Pituitary
• Special neurons in hypothalamus synthesize & secrete
neurohormones called:
– Releasing hormones (Librins)
– Inhibiting hormones (statins)
• These hormones are carried by hypothalamohypophysial portal vein
into adenohypophysis
• Thus:
•  Secretion from neurohypophysis is controlled by nerve signals
– that originate in the hypothalamus & terminate in the
neurohypophysis
But
•  Secretion by adenohypophysis is controlled by hormones called:
– hypothalamic releasing hormones (librins) & inhibitory hormones
(statins)

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• All or most of the hypothalamic hormones are secreted at nerve endings in the median
eminence  Transported to the anterior pituitary gland

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Peripheral endocrine glands
• 1. Thyroid Gland
 Located below the larynx on each side of and anterior to the trachea
 Weighing 15 to 20 grams in adults
 have two secretary cells:
A. follicular cells
 Secretes two major hormones, thyroxine (T4) and triiodothyronine (T3)
 Profoundly increase the metabolic rate of the body
 Increase the basal metabolic rate to 60-100% above normal
 Also secretes calcitonin for Ca++ homeostasis
B. parafollicular cells
secrete calcitonin that regulate Ca++ homeostasis

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• Clinical correlates
• Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves' Disease)
• Causes
– 2-3 times normal size, with tremendous hyperplasia and
– infolding of the follicular cell lining into the follicles
– So that the number of cells is increased greatly
– Also, each cell increases its rate of secretion
• severalfold - 5 to 15 times normal
• Similar to those caused by excessive TSH,
• however, plasma TSH concentrations are less than normal

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•  Substances that have actions similar to those of TSH are found in blood
of almost all patients
•  Immunoglobulin antibodies that bind with the same membrane receptors
that bind TSH.
•  Induce continual activation of the cAMP system of the cells
•  With resultant development of hyperthyroidism
•  Thyroid-stimulating immunoglobulin (TSI)
– Have a prolonged stimulating effect on the thyroid gland,
• lasting for as long as 12 hours, in contrast to a little over 1 hour
for TSH
 High level of thyroid hormone suppresses formation of TSH
•  Antibodies that cause hyperthyroidism occur as a result of:
– autoimmunity that has developed against thyroid tissue

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• Thyroid Adenoma
•  Localized adenoma (a tumor) that develops in the thyroid tissue
and
– secretes large quantities of thyroid hormone
•  This is different from the more usual type of hyperthyroidism, in
that:
– it usually is not associated with evidence of any autoimmune disease
•  An interesting effect of adenoma is that:
– as long as it continues to secrete large quantities of thyroid hormone
–  secretory function in the remainder of the thyroid gland is totally
inhibited
– b/c thyroid hormone from adenoma depresses production of TSH

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• Symptoms of Hyperthyroidism
– high state of excitability
– intolerance to heat
– increased sweating
– mild to extreme weight loss (sometimes as much as 100 pounds)
– varying degrees of diarrhea
– muscle weakness
– nervousness or other psychic disorders
– extreme fatigue but inability to sleep
– tremor of the hands

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•  Most people with hyperthyroidism develop some degree of
protrusion of the eyeballs called exophthalmos
•  Occurs in about one third of hyperthyroid patients
•  Sometimes becomes so severe that the eyeball protrusion
stretches
optic nerve enough to damage vision
•  Eyes are damaged b/c
– eyelids do not close completely when the person blinks or is asleep
– Epithelial surfaces of the eyes become dry and irritated and often infected,
resulting in ulceration of the cornea.
• Cause: edematous swelling of retro-orbital tissues & degenerative
changes in extraocular muscles
• In most patients, immunoglobulins can be found in blood that reacts
with the eye muscles

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• Hypothyroidism
• Effects - opposite to those of hyperthyroidism
• Physiologic mechanisms peculiar to hypothyroidism
•  Probably initiated by autoimmunity against thyroid gland,
• but immunity that destroys the gland rather than stimulates it
• Thyroid inflammation

 fibrosis of the gland

•  with resultant diminished or absent secretion of thyroid hormone
•  Several other types of hypothyroidism also occur, often associated
with development of enlarged thyroid glands, called thyroid goiter

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• Mechanism for development
•  Lack of iodine prevents production of both T3 & T4
•  No hormone is available to inhibit production of TSH
•  Secretion of excessively large quantities of TSH
•  TSH stimulates thyroid cells to secrete tremendous amounts of
thyroglobulin colloid into follicles,

• the gland grows larger and larger
•  But because of lack of iodine, T3 & T4 production does not occur

– therefore does not cause normal suppression of TSH production
•  Follicles become tremendous in size, and thyroid gland may increase
to 10 to 20X normal size

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Idiopathic Nontoxic Colloid Goiter
• Enlarged thyroid glands similar to those of endemic colloid goiter can
• Exact cause is not known,
• but most of these patients show signs of mild thyroiditis

•  causes slight hypothyroidism

•  increased TSH secretion

•  growth of noninflamed portions of gland
•  This could explain why these glands usually are nodular,
– with some portions of the gland growing
– while other portions are being destroyed by thyroiditis

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Cretinism
•  Caused by extreme hypothyroidism during fetal life, infancy, or childhood
•  Characterized by failure of body growth and by mental retardation
•  Results from:
– Congenital lack of a thyroid gland
– Failure of the thyroid gland to produce thyroid hormone
• because of a genetic defect of the gland - congenital cretinism
– Iodine lack in the diet (endemic cretinism)

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Hypothyroidism
Cretinism - occurs if the hyposecretion is during fetal or early
developmental life.
• - results in reduced metabolism
• - results in reduced growth
• - results in mental retardation
Myxedema - occurs if the hyposecretion is during adult life
• Causes bagginess in the eyes and swelling of face.
• results in reduced metabolism
• results in reduced mental & physical activity
• results in increased blood pressure
• results in accumulation of subcutaneous fluids

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Parathyroid Gland
Calcium and Phosphate Regulation
•  ECF Ca concentration is regulated very precisely;
– normal value of about 9.4 mg/dl = 2.4 mmol/L
• plays a key role in many physiologic processes
– Contraction of skeletal, cardiac, and smooth muscles
– Blood clotting
– Transmission of nerve impulses
•  Hypercalcemia cause progressive depression of nervous system
•  Hypocalcemia cause nervous system to become more excited
• Only about 0.1% of total body Ca is in ECF,
– 1% is in cells, and
– the rest is stored in bones.
• Approximately 85% of the body's phosphate is also stored in bones,
• 14-15% is in the cells, and less than 1% is in ECF

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• Calcium in the plasma
•  41% (1 mmol/L) combined with plasma proteins
•  9% (0.2 mmol/L) combined with anionic substances
•  50% of Ca in plasma is both diffusible through capillary membrane and ionized
•
•  Inorganic phosphate in the plasma in two forms: HPO4- and H2PO4-

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Physiology of parathormone
• PTH increases Ca & Phosphate absorption from Bone
• PTH has 2 effects on bone in causing absorption of Ca and phosphate
• PTH Decreases Calcium and Increases Phosphate Excretion
• Administration of PTH causes rapid loss of phosphate in the urine
– By diminish proximal tubular reabsorption of phosphate ions
• PTH Increases Intestinal Absorption of Ca and Phosphate
•  PTH greatly enhances both Ca and phosphate absorption from the intestines
– by increasing the formation of 1,25-dihydroxycholecalciferol from vitamin D
• in the kidneys

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• Calcitonin
•  Peptide hormone secreted by thyroid gland, tends to  plasma [Ca]
– has effects opposite to those of PTH
•  Quantitative role of calcitonin is far less than that of PTH
• Synthesis and secretion
•  In parafollicular cells, or C cells,
– lying in interstitial fluid between follicles of thyroid gland
•  Primary stimulus for calcitonin secretion is  plasma [Ca++]
–  This contrasts with PTH secretion, which is stimulated by [Ca++]
–  In young animals an  in plasma [Ca++] of 10% causes an immediate
twofold or more  in the rate of secretion of calcitonin
•  This provides a second hormonal feedback mechanism for controlling
plasma [Ca++]

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Clinical correlates
Hypoparathyroidism
• Parathyroid glands do not secrete sufficient PTH,
• Osteocytic reabsorption of exchangeable Ca decreases and osteoclasts become
almost totally inactive
– Ca reabsorption from bones is depressed  level of Ca in body fluids
decreases
• bone usually remains strong
• parathyroid glands are suddenly removed  [Ca] falls from
9.4 mg/dl to 6 to 7 mg/dl within 2 to 3 days,
 this low calcium level develop tetany
–  Among the muscles of the body especially sensitive to tetanic spasm are
the laryngeal muscles
–  Spasm of these muscles obstructs respiration,
• the usual cause of death in tetany unless appropriate treatment is applied

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• Primary Hyperparathyroidism
•  An abnormality of the parathyroid glands causes inappropriate,
excess PTH secretion
• Cause:
– Tumor of one of the parathyroid glands;
– such tumors occur more frequently in women than in men or children
• Because pregnancy and lactation stimulate parathyroid glands and
• therefore predispose to the development of such a tumor
• Hyperparathyroidism causes extreme osteoclastic activity in the bones

•  elevates [Ca++] & depressing concentration of phosphate

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• Bone disease of hyperparathyroidism
•  Bone show extensive decalcification
•  Multiple fractures of weakened bones can result from only slight trauma
• The cystic bone disease of hyperparathyroidism is
called osteitis fibrosa cystica
• Hyperparathyroidism cause the plasma Ca level to rise to 12 to 15 mg/dl
– Effects of elevated Ca levels:
• Depression of central and peripheral nervous systems
• Muscle weakness
• Constipation,
• abdominal pain,
• lack of appetite, and
• depressed relaxation of heart during diastole

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• Secondary Hyperparathyroidism
•  High levels of PTH occur as a compensation for hypocalcemia rather than as a
primary abnormality of the parathyroid glands
–  This contrasts with primary hyperparathyroidism,
• which is associated with hypercalcemia.
•  Caused by vitamin D deficiency or chronic renal disease
– damaged kidneys

• unable to produce sufficient amounts of active form of vitamin D,
– 1,25-dihydroxycholecalciferol

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Adrenal gland
Adrenal gland – suprarenal glands
• Two adrenal glands,
– each of which weighs about 4 grams,
– lie at the superior poles of the two Kidneys – suprarenal glands
• Composed of two distinct parts
– Adrenal medulla (inner or central zone of the gland, 20%)
• Functionally related to the SNS
• Epinephrine and norepinephrine in response to sympathetic
stimulation
– Adrenal cortex (outer zone)
• secretes an entirely different group of hormones, called
corticosteroids

37. • Two major types of adrenocortical hormones
• 1. Mineralocorticoids
• Gained this name b/c they affect electrolytes ("minerals") of
ECF-sodium and potassium, in particular
• 2. glucocorticoids.
• Gained their name because they exhibit important effects that
increase blood glucose concentration
• Additional effects on both protein and fat metabolism
• More than 30 steroids have been isolated from the adrenal
cortex, but two are of exceptional importance - aldosterone and
cortisol
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Biological action of the Glucocorticoids
• 95 % of the glucocorticoid activity of the adrenocortical secretions
results from the secretion of cortisol
• In addition, a small but significant amount of glucocorticoid activity is
provided by corticosterone
• Effects on Carbohydrate Metabolism
– Stimulate gluconeogenesis,
• this results mainly from two effects of cortisol
1. Cortisol enzymes required to convert amino acids into glucose
2. Cortisol causes mobilization of amino acids
• As a result, more amino acids become available in the plasma to
enter into the gluconeogenesis process.
– Decreased glucose utilization by cells
– Elevate blood [glucose] and "adrenal diabetes."

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Abnormalities of Adrenocortical Secretion
1. Hypoadrenalism- Addison's Disease
• Results from failure of adrenal cortices to produce adrenocortical
hormones
• Cause:
a. primary atrophy of the adrenal cortices
• Atrophy is caused by autoimmunity against the cortices
b. Adrenal gland hypofunction
• caused by destruction of the adrenal glands due to
• tuberculosis or invasion of the adrenal cortices by cancer
Disturbances in Addison's disease
• Lack of aldosterone secretion
 ECF fluid becomes depleted,
 plasma volume falls,
 red blood cell concentration raises markedly,
 cardiac output decreases, and the patient dies in shock.
• Impossible to maintain normal blood [glucose] between meals
•  No synthesize of significant amount of glucose by gluconeogenesis

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2. Hyperadrenalism- Cushing's Syndrome
• Most of the abnormalities of Cushing's syndrome are ascribable
to abnormal amounts of cortisol - Hypercortisolism
• Causes:
1. Adenomas of anterior pituitary

large amounts of ACTH  adrenal hyperplasia  excess cortisol secretion
2. Abnormal function of hypothalamus

high levels of CRH  excess ACTH
3. "ectopic secretion" of ACTH by a tumor elsewhere in the body
4. Adenomas of the adrenal cortex
 Cushing's syndrome can also occur when large amounts of
glucocorticoids are administered

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ENDOCRINE PANCREASE
•  Pancrease has two major types of tissues
 acini – produce pancreatic juice
 islets of Langerhans
• Islets contain 4 types of cells
• Alpha - about 25% of the total
– secrete glucagon
• Beta- Constituting about 60%
– Lie mainly in the middle of each islet
– Secrete insulin
• Delta- about 10% of the total
– secrete somatostatin
• PP cells- present in small numbers in the islets
– secretes called pancreatic polypeptide
• a hormone of uncertain function

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• Insulin and Its Metabolic Effects
•  Has a profound effect on carbohydrate metabolism
•  Affects fat & protein metabolism
– almost as much as it does carbohydrate metabolism
• Great abundance of energy-giving foods in the diet is carbohydrates
–  Insulin is secreted in great quantity in response to high [glucose]
• It causes glucose to be stored as glycogen
– mainly in the liver and muscles
•  Excess glucose that cannot be stored as glycogen are converted into
fats
– under the stimulus of insulin and
– stored in the adipose tissue

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• Insulin binds with  subunits

•  subunits auto phosphorylated
• Autophosphorylation of  subunits
activates a local TK
– phosphorylation of multiple
other intracellular enzymes
• including a group called IRS
• In this way, insulin directs the IC
metabolic machinery
– to produce the desired effects
on;
• carbohydrate,
• fat, &
• protein metabolism

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Mechanisms of Insulin Secretion
• The  cells have a large number of glucose transporters (GLUT-2)
– GLUT2 permits a rate of glucose influx
• that is proportional to the blood [glucose] in the physiologic
range.
• Inside the cells, glucose is phosphorylated to glucose-6-phosphate
– by glucokinase,

• the G-6-P is subsequently oxidized to form ATP,
– ATP inhibits the ATP-sensitive K channels of the cell
• - Closure of the K channels depolarizes the cell membrane,

• opening voltage-gated Ca channels, (sensitive to changes in voltage)

• Influx of Ca, stimulates;
– fusion of insulin-containing vesicles with cell membrane and
– secretion of insulin into the ECF by exocytosis

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Mechanisms of Insulin Secretion

46. 46
• v

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• Insulin is The Only Hormone that Can Lower Blood Glucose
– Muscle, fat & liver tissues require insulin
• to transport glucose into the cells;
• in these tissues insulin seems to  the # of GLUT2 in the cell
membrane
• Many other tissues, like brain, do not require insulin to transport
glucose
– Insulin also  activity of enzymes that cause storage of
sugar as glycogen or lipid
– After a meal blood sugar rises  stimulates the release of insulin;
• Extra insulin then causes the sugar to enter the cells & become
stored
• Several Hormones Can Raise Blood Glucose
– Four major hormones raise blood glucose:
• Glucagon, Cortisol, Epinephrine, Growth hormone
– In vigorous exercise all 4 of these hormones increase

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Diabetes Mellitus
• is a syndrome of impaired carbohydrate, fat, & protein metabolism
• caused by:
– either lack of insulin secretion or
– decreased sensitivity of the tissues to insulin.
• There are two general types of diabetes mellitus:
• Type I diabetes, also called insulin-dependent diabetes mellitus (IDDM)
– is caused by sever, absolute lack of insulin secretion
• Results from reduction in the  cell mass
– due to autoimmune destruction of  cells
– assumed to occur following an environmental trigger in genetically
susceptible individuals
– may develop very abruptly, over a period of a few days or weeks, with three
principal sequelae:
• 1. Increased blood glucose
• 2. Increased utilization of fats for energy & for formation of cholesterol by the
liver
• 3. Depletion of the body's proteins.
– Age of onset is <20 years, hence called juvenile onset DM

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• Type II diabetes,- 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.
– More common than type I, accounting for about 90% of all cases
of diabetes mellitus.
• Type II diabetes, in contrast to type I, is associated with increased
plasma [insulin] = (hyperinsulinemia).
– This occurs as a compensatory response by the pancreatic  cells
for diminished sensitivity of target tissues to the metabolic
effects of insulin,
– this condition referred is to as insulin resistance.
• The  in insulin sensitivity impairs carbohydrate utilization and
storage,
– raising blood glucose & stimulating a compensatory increase in
insulin secretion.