A endocrine-mrmc-to be used.ppt

Endocrine Physiology
For
Body control and
regulation

Human
Endocrine
Glands
• In the brain:
• Hypothalamus
• Pituitary gland
• Pineal gland
• Adrenal gland
• Pancreas
• Ovary
• Testis

Endocrine action
 Endocrine system controls
physiology via chemical signals from
one part of the body to another
 Target cell undergoes a biological
response

Cell to Cell Signaling
AUTOCRINE

AUTOCRINE
PARACRINE

AUTOCRINE
PARACRINE
ENDOCRINE

 Neurocrine - neural
cells that release
chemical signals into
the bloodstream

Fashions of cellular Signaling

Figure 18.1
The Endocrine System

FUNCTIONS
1. Regulate metabolic processes
2. Regulate rate of chemical reactions
3. Transport of substances thru membrane
4. Regulate water and electrolyte balance, blood
pressure
5. Vital roles in reproduction, development, growth

Classification of Hormones
1. Based upon chemical nature
2. Based upon function

Chemical Nature of Hormones
Hormones are
Peptides
Steroid
Amino Acid Derivatives

Chemical Classification of Hormones
1. Amino hormones
-derived from tyrosine
2. Peptide and protein hormones
- Made up of peptide
3. Steroid hormones
– derived from cholesterol

Proteins & polypeptides
Pituitary, Pancreas, Parathyroid.
b. Steroids
Adrenal cortex and Sex hormones.
c. Amino acid derivatives
Adrenal Medulla, Thyroid hormones.
Classification of hormones

Functional classifications
1. Releasing hormones
2. tropic (or Stimulating) hormones
3. Non-tropic hormones

Hypothalamus
Pituitary gland
Releasing hormones
Peripheral endocrine glands
Stimulating hormones
Hormonal axis
Hormones
Peripheral organs
BRAIN

Hormone types
1. Polar:
• Most hormones.
• Bind to receptor protein on plasma
membrane.
2.Lipophilic (non polar):
• Cross plasma membrane, act inside target
cells.
• Steroid hormones and thyroid hormones.

Second messengers
Second messengers include
– cAMP or cGMP
– phospholipids diacylglycerol and inositol
triphosphate (DAG and IP3)
– calcium

Lipophilic hormones
- Inside cell: bind to nuclear hormone
receptors.

Transcription factors
• Transcription:
DNA is transcribed into messenger
RNA.
This mRNA will then be translated
(by ribosomes) into proteins!

Regulation of receptor
1. Down regulation (desensitization):
when hormone production is
increasing
2. Up regulation: when hormone
production is decreasing

Hypothalamic-Pituitary Axis
– Hypothalamic-Pituitary-Thyroid axis (HPT)
– Hypothalamic-Pituitary-Adrenal axis (HPA)
– Hypothalamic-Pituitary-Gonadal axis
(HPG)

Control of Hormone Secretion
1. Negative Feedback mechanism
2. Positive Feedback mechanism

Positive Feedback Control
Parturition and suckling
•

Anterior and posterior pituitary glands.

Anterior pituitary cells and hormones
Cell type Pituitary
population
Product Target
Corticotroph 15-20% ACTH Adrenal gland
Adipocytes
Melanocytes
Thyrotroph 3-5% TSH Thyroid gland
Gonadotroph 10-15% LH, FSH Gonads
Somatotroph 40-50% GH All tissues, liver
Lactotroph 10-15% PRL Breasts
gonads

Hormones of the Anterior Pituitary
1. Growth hormone (GH)
2. Prolactin
3. Thyroid stimulating hormone (TSH)
- also called thyrotropin
- stimulates milk production
- one of the growth promoting hormones

Hormones of the Anterior Pituitary con’t
4. Adrenocorticotrophic hormone (ACTH)
5. Leutinizing hormone (LH)
6. Follicular stimulating hormone (FSH)
- stimulates follicular development
- promotes ovulation
- also called corticotropin

Hypothalamic Control of the Anterior Pituitary

GH or Somatotropin
Secreted by somatotropes
Done indirectly – liver produces –
somatomedins or IGF’s – insulin growth
factors

GH-IGF actions
1.Protein synthesis
• GH enhances amino acid transport into cells
• Ensures protein anabolism
• Suppresses protein catabolism
• Protein sparing effect

2.Lipid metabolism
• Release free fatty acids and glycerol
• FFA’s used for energy
• Provides energy
•3.Carbohydrate metabolism
• Glucose sparing effect

Physiological function of GH (somatotropin) :
↑Plasma FFA
↑Plasma glucose
↓Plasma amino acids
↓ Plasma urea
Metabolism
Condrocytes
↑Amino acid uptake
↑Protein synthesis
↑DNA,RNA synthesis
↑Chondroitin sulfate
↑Cell size and number
↑Linear growth
Muscle
↓ Glucose uptake
↑Amino acid uptake
↑ Protein synthesis
↑Lean body mass
Adipose tissue
↓Glucose uptake
↑Lipolysis
↓ adiposity
Kidney, pancreas, intestine, islets,
parathyroids, connective tissue,
bone, heart, lungs
↑Protein synthesis
↑DNA,RNA synthesis
↑Cell size and number
↑Organ size
↑Organ function
Growth
hormone

Control of GH secretion
SS GHRH
GH
IGF-1
Target tissue
⊕
○
-
⊕
⊕
-
○
Somatostatin: SS
Somatotropin: GH
Somatomedin: IGF-1

Regulation of Growth Hormone
Secretion
• GH secretion controlled primarily by
hypothalamic GHRH stimulation and
somatostatin inhibition

Abnormalities of GH secretion :
– Pituitary dwarfs are a result of
hyposecretion of GH
– Gigantism results from juvenile
hypersecretion
– Acromegaly results from adult
hypersecretion of GH

Hypothalamic Control of Posterior Pituitary
(ADH)
(Oxy)

Posterior lobe
• Produces No Hormones .
• Stores and releases OT and ADH

posterior lobe (neurohypophysis)
 Neurons of the supraoptic nucleus manufacture
antidiuretic hormone (ADH)
1. Decreases the amount of water lost at the kidneys
2. Elevates blood pressure

posterior lobe (neurohypophysis)
 Neurons of the paraventricular nucleus
manufacture oxytocin
1. Stimulates contractile cells in mammary glands
2. Stimulates smooth muscle cells in uterus

Physiological effects of ADH :
1. The retention of water in excess of
solute by the kidney
2. In large doses, vasopressin elevates
arterial blood pressure

ADH (antidiuretic hormone):
• Stimulates fusion of aquaporin (water channel)
vesicles in the collecting duct.
• Results in (increased permeability to H20 and )
increased reabsorption of water.

Mechanism of Vasopressin Action
Figure 20-6: The mechanism of action of vasopressin

• The two major stimuli of ADH secretion:
1. Changes in plasma fluid volume
2. changes in Plasma osmolarity.
• Hypovolemia sensitizes the ADH response
to hyperosmolarity.
Secretion of ADH

Regulators
of
Vasopressin
Release

Neuroendocrine reflexes
• release hormones – nervous system signal
1. dehydration > osmolarity of blood – osmoreceptors
detect – ADH released = water conservation
2. >BP –stimulates stretch receptors in heart & certain
arteries – inhibits ADH release, > urine output, < BP

Diabetis insipidus
1.Neurogenic Diabetes insipidus
2. Nephrogenic diabetes insipidus
Clinical implications of ADH:

Diabetes Insipidus - clinical features:
• polyuria- 3-15 L/day
• SG < 1.005
• urine osmolality <200 mOsm/kg
• plasma osmolality > 287 mOsm/kg
• polydipsia

1.In uterus during parturition
2.In mammary gland during lactation
Oxytocin

“Positive feedback loop”
Oxytocin↑
Uterine
contraction
Cervix
dilation
Labor
Oxytocin receptor
↑x100
Estradiol
⊕
⊕

Oxytocin
1. Childbirth – labor contractions – smooth muscle –
uterus
2. Lactating mothers – milk let-down effect
3. Surges –sexual arousal and orgasm – m & f
4. Feelings sexual satisfaction and emotional bonding

Control of oxytocin secretion
• Stimuli:
• Stimulation of the “touch receptor”
1. Around the nipples Milk let-down or
“milk ejection reflex”
2. Genital tract stimulation

Neuroendocrine reflexes
• Infant suckling – hypothalamus – release OT = milk
ejection
• Cerebral cortex – trigger neuroendocrine reflexes
• Examples – lactating mother hears baby cry = milk
ejection reflex

Thyroid Gland
 found in neck region
Weighs about 15-25gm &has rich blood
supply (4-6ml/gm/min).
Made up of multiple acini / follicles.
 Between follicles “C cells/parafollicular cells ”
are present Calcitonin.

 Each follicle contains proteinaceous material
called colloid which contains Thyroglobulin.
Follicular cells secrete T4 & T3.

Bio-synthesis of thyroid hormones:

Synthesis of thyroglobulin on ribosome of ER.
i. Iodide trapping (NIS)
 Trapping is brought by active transport (Iodide
pump) and Na+-K+-ATPase
 TSH stimulates both iodide pump Na+-K+-
ATPase

iii. Oxidation of iodide ion:
Iodide converted to oxidized form of iodine

iv. Iodination of tyrosine & formation of thyroid
hormones .
Binding of iodide with thyroglobulin is called
“organification of thyroglobulin”.
Tyrosine
Iodinase
MIT & DIT
MIT + DIT  T3
DIT + DIT  T4
Coupling
reactions
Thyroid peroxidase is probably involved in coupling
& Iodination.

Storage of thyroglobulin (Tg):
Tg  30 T4 + few T3 molecules.
Large amount of thyroid hormones are stored in
this form which is sufficient for 2-3 months.

Secretion of Thyroid Hormones
 Stimulated by TSH
 Endocytosis of colloid on apical membrane
 Coupling of MIT & DIT residues
 Catalyzed by TPO (thyroid peroxidase)
 Hydrolysis of Thyroglobulin
 Release of T3, T4
 the T4:T3 ratio is as high as 20:1

Transport of thyroid hormones
 Majority of circulating hormone is T4
 98.5% T4
 1.5% T3
 Total Hormone load is influenced by serum
binding proteins (TBG, Albumin, TBPA)
 Thyroid Binding Globulin (TBG) 70%
 Albumin 15%
 Thyroid Binding PreAlbumin (TBPA) 10%
 Regulation is based on the free component of
thyroid hormone

Activation and Degradation of Thyroid
Hormone
 T3 and T4 bind to the same nuclear receptor but T3 binds with
10 times more affinity than T4.
 Thus, because it has greater affinity for the receptor, T3 is the
more active form of thyroid hormone.
 Many target tissues can regulate the conversion of T4 to either
T3 or rT3, thereby locally controlling hormone activity.
 Most of the circulating T3 is derived from the peripheral
conversion of T4 into T3 and its release again into the
circulation (e.g., liver, kidney, and skeletal muscle).

Actions of Thyroid hormones
 Metabolic actions
On various systems
On Growth
 Interaction with Catecholamines

1. Metabolic Actions :
A. Calorigenic
 Increases O2 consumption & heat production by
stimulating Na+-K+-ATPase
 Increases BMR.
 Heat sensitivity in Hyperthyroidism.
 Some of calorigenic actions are due to lipolytic effect

B. Carbohydrate Metabolism :
Hyperglycemic.
 Increase rate of reabsorption of glucose from GIT
 Increases glycogenolysis in liver, muscle.
 Increase gluconeogenesis.
 Reduces secretion of insulin & accelerates its
breakdown.
 promotes Diabetes.

C. Fat metabolism :
Promotes cholesterol synthesis , but also promotes
hepatic breakdown & biliary excretion of cholesterol.
Increases fecal excretion of cholesterol.
Reduction in plasma cholesterol levels.
Causes lipolysis, promotes fatty acid oxidation
by the cells.
i.e. breakdown > synthesis.
 Therapeutically used to lower cholesterol levels

D. Protein metabolism :
 stimulate both structural and functional protein
synthesis.

2. On Various systems :
a.Blood :
Stimulates erythropoiesis.
Hyperpolycythemia.
Hypo anemia.

c. Respiration :
Rate of metabolism
Utilization of O2 & formation of Co2
Rate & Depth of respiration.

d. GIT :
Increases appetite & food intake.
Increases motility & secretions.
 Hyper food intake motility  Diarrhoea.
 Hypo food intake motility  Constipation.

e. On Skin :
Hyper  Excess heat
Sweat production.
Cutaneous vasodilation.
Skin is soft , warm & wet.
Hypo skin is coarse, dry, scaly, cold & puffy.
Hypersensitive to cold.

f. On CNS :
Essential for normal development &growth of CNS.
In adult brain TH’s stimulate :
Branching of dendrites.
Myelination.
Increases no. of synapses.
In fetus & newborn stimulate growth of brain.

3. On growth :
Required for normal growth & differentiation
from the 1st day of newborn.
GH requires thyroxine to exert its full effect.
T3 has direct growth promoting effect .
4. Interaction with Catecholamines :
 TH’s sensitizes the tissues to catecholamines
by increasing no. of receptors on cells.

TRH
 Produced by Hypothalamus
 Down regulated by T4, T3
 Travels through portal venous system to
adenohypophysis
 Stimulates TSH formation

TSH
 Produced by Adenohypophysis Thyrotrophs
 Upregulated by TRH
 Downregulated by T4, T3
 Stimulates several processes
 Iodine uptake
 Colloid endocytosis
 Growth of thyroid gland

Wolff-Chaikoff Effect
 Increasing doses of I- increase hormone synthesis
initially but higher doses cause cessation of
hormone formation.

Hypothyroidism
 Symptoms – fatigability, coldness, weight gain,
constipation,
 Signs – Cool skin, dry skin
 Newborn – Retardation, short stature, possible
deafness
 Types of Hypothyroidism
 Primary – Thyroid gland failure
 Secondary – Pituitary failure
 Tertiary – Hypothalamic failure

Causes :
1.Congenital deficiency of the gland.
2. Iodine deficiency in mother during pregnancy.
3. Administration of Anti-Thyroid drugs during
pregnancy.
Cretinism

Hashimoto thyroiditis
 Hypothyroidism is most commonly caused by,
an autoimmune disease
 autoimmunity destroys the gland rather than
stimulates it

Hyperthyroidism
 Symptoms – Palpitations, nervousness, fatigue,
diarrhea, sweating, heat intolerance

Graves disease
 Most common cause of hyperthyroidism
 It is autoimmune disease
 Thyroid-stimulating immunoglobulin (TSI) binds
with the same receptors that bind with TSH

Changes in Feedback Relationships in Several
Disorders

Calcium Regulation
Parathyroid gland

Calcium
 Required for muscle contraction,
intracellular messenger systems,
hemostasis, membrane excitation,
excitation secretion process of hormone &
enzymes.
 Exists in free (ionized) and bound states
 Albumin (40% total calcium)
 Phosphate and Citrate (10% total calcium)
 Concentration of Ca2+ mediated by
 Parathyroid gland
 Parafollicular C cells of thyroid gland
 Kidney & Bone.

Calcium Distribution in the Body

Parathyroid Gland
Parathyroid glands contains chief cells which
secrete parathyroid hormone (PTH).
Its primary function is to keep the Ca2+ conc. In
ECF & ICF nearly constant level.

Actions :
1.On Bones :
 Increases plasma calcium & decreases plasma
phosphate conc. by osteolytic effect.
 increases Osteoclast size, no. of osteoclast nuclei
& osteoclast proliferation.
 Hydrolyzes the organic bone matrix.

2. On Kidneys :
Increases Ca2+ reabsorption from DCT.
Decreases Ca2+ excretion in urine.
Decreases reabsorption of phosphate from PCT &
increases its excretion in DCT.
Promotes conversion of 25 HCC to 1,25 DHCC by
activating 1 hydroxylase.

3. On GIT :
Enhances both Ca2+ & PO4
- absorption by
increasing production of 1,25 DHCC.

Regulation :
Stimulation of parathyroid
PTH
Mobilization of Ca2+
from bones
Normal serum Ca2+
Serum Ca2+
1.

2. Serum phosphate
PTH
Serum Ca2+
3. 1,25 DHCC inhibits PTH
secretion

calcitonin
•It regulates calcium level in the blood
•Secreted from “C cells/ parafollicular cells” of
thyroid gland.

Actions :
 Decreases plasma Ca2+ & PO4
- conc.
 Inhibits Osteoclast activity& its number.
 Decreases renal formation of 1,25 DHCC.
 Inhibits intestinal absorption of Ca2+ & PO4
- .

Vitamin-D
Plasma PO4
- concentration

rickets
•Result of Vit-D deficiency.
•Causes : Inadequate intake of vit-D, Inadequate
exposure to sun, kidney failure, liver dysfunction,
defect in target cell receptors.
•Pathology : Deficiency in deposition of Ca2+ salts in
bones, process of Ossification is abnormal.

Osteomalacia
 Adult rickets.
 Inadequate absorption of Ca2+ due to deficiency
of vit-D & Ca2+ in diet.
 Serum Ca2+ is low , 6-7mg/dl.
 Mostly seen in females after multiple pregnancies.

Regulation of Calcium and phosphate

Adrenal Glands
Paired
organs that
cap the
kidneys.
Each: outer
cortex and
inner
medulla.

Adrenal cortex
Adrenal cortex:
- stimulated by ACTH
- secretes corticosteroids
- different regions secrete different hormones.
- all made from cholesterol.

Adrenal Cortex
Corticosteroids include:
- mineralocorticoids:
- glucocorticoids
- gonadocorticoids

Adrenal Cortex
Mineralocorticoids:
- aldosterone
- targets kidneys
- affects Na+ and K+ balance
- stimulates transcription of Na+/K+ ATPase
pump!
- more aldosterone -> more Na+, water in body
- stress -> CRH -> ACTH -> aldosterone ->
retain fluid -> high blood pressure!

Adrenal Cortex
Glucocorticoids
- cortisol
- metabolism, more glucose in blood
- stress -> large increase in glucocorticoides

Adrenal Cortex
Gonadocorticoids:
-sex steroids
- include DHEA (precursor for estrogen,
testosterone)

Cortisol Actions :
 Metabolic actions
On various systems
Anti-inflammatory & Anti-immunity
Stress adaptation
Anti-growth effects
Permissive actions

1.Metabolic actions :
Carbohydrate metabolism :
glucose sparing hormone, anti-insulin effects.
Increases hepatic glycogenolysis 6-10 fold.
Decreases rate of glucose utilization.
 Adrenal Diabetes

Fat metabolism :
Lipolytic .
Increases plasma FFA by promoting mobilization
of fatty acids from adipose tissue.
Enhances oxidation of fatty acids in the cells.
Protein metabolism :
catabolic
Reduces protein stores

Electrolyte & H20 metabolism :
Actions similar to Aldosterone, less potent.
Retention of Na+ & Cl-.
Excretion of K+ .
Maintains ECF volume, provides adequate GFR

2. On various Systems :
1.CVS :
Required for maintenance of normal BP.
Improves myocardial performance by blocking Na+-
Ca++ exchanger.
Permissive action to catecholamine's & A-II
Cortisol stimulates erythropoietin synthesis

2.GIT :
Promotes peptic ulcer formation (mediated
stimulation of gastric acid and pepsin secretion)
Promotes absorption of water insoluble fats .
exerts a trophic effect on the GI mucosa
Stimulates appetite, hypercortisolism is
frequently associated with weight gain

3.Muscle :
Maintains the contractility & work performance
skeletal and cardiac muscle.
Increases ß adrenergic receptors in myocardium.
When cortisol levels are excessive, muscle
weakness and pain are common symptoms
(excessive proteolysis)
4. Connective tissue :
Inhibits collagen synthesis and produces thinning
of skin and walls of capillaries.

5.Bone :
Increases bone resorption .
decrease intestinal Ca++ absorption and renal
Ca++ reabsorption, Antagonizes the action of Vit-D.
inhibit osteoblast bone-forming functions
(osteoporosis)
6. On Foetus :
Facilitates inutero maturation of CNS, retina, skin,
GIT & lungs.
Increases rate of development of alveoli, increases
surfactant synthesis.

3. Anti-inflammatory & anti-immunity action :

4. Stress adaptation
Stress  ACTH  Cortisol
5. Permissive actions : (Glucagon & catecholamines)
Permissive actions of cortisol include
1. Glucagon & catecholamines to exert
calorigenic effects.
2. Catecholamines to exert lipolytic effects
3. Catecholamines to produce pressor response
& bronchodilation.

6. Anti-growth Effect :
antagonize action of vit-D
1.Decreases Ca++ reabsorption
2.Inhibit mitosis of fibroblasts
3.Cause degradation of collagen
Osteoporosis
Delays wound healing

Regulation of Cortisol secretion :

Cushing syndrome
Hypercortisolism regardless of origin, including
chronic glucocorticoid therapy
It is a clinical disorder which results from
the exposure of body tissues to sustained
supraphysiological blood levels of cortisol.

Causes of hypercortisolism
1. Primary hypercortisolism (adrenal source)
 ACTH independent
Cortisol elevated, ACTH depressed
Adenomas or carcinomas of adrenal cortex
2. Secondary hypercortisolism (pituitary vs. ectopic source)
ACTH dependent
Elevated ACTH, cortisol, adrenal androgen
Benign or malignant ACTH secreting tumors.
Ectopic ACTH syndrome:
° Most frequently in patients with small cell carcinoma of the
lung (Greater secretion of ACTH)

Cushing’s Syndrome symptoms
– Thin skin, easy bruising
– Osteoporosis
– Diabetes
– Excess hair growth
– Irregular periods
– Problems in conceiving
– High blood pressure
– Fluid retention
 changes in protein and
fat metabolism
 changes in sex
hormones
 salt and water retention

Aldosterone
Produced in the zona glomerulosa
of the adrenal cortex

Aldosterone actions
1.Na+ & H2O reabsorption  on CD & late DCT.
2. K+ secretion with Na+ reaborption.
3. H+ secretion with Na+ reaborption.
3. Infusion of small doses causes increase BP.
4. Enhances Na+ absorption especially in colon,
which prevents loss of Na+ in stools.

Control of Aldosterone
Release
ADRENAL CORTEX
Aldosterone
ECV
 K+
Renin
Renin Substrate
(Angiotensinogen)
Angiotensin I
Angiotensin II
decrease BP
 Δ Na+
Macula
Densa
ACE
ACTH
 K+

Aldosterone Syndromes
Over production
Conn’s Syndrome
Underproduction
Addison’s Syndrome

Primary Aldosteronism :Conn’s Syndrome
 It is a condition in which there is prolonged
excessive secretion of aldosterone from an
adrenocortical adenoma .
Features :
Hypernatremia, Hypokalemia, Hypervolemia,
Hypertension.

Secondary Aldosteronism :
 It is a condition in which oversecretion of
Aldosterone is brought about by extra adrenal
factors.

Adrenal cortex Insufficiency
 Destruction of adrenal cortex
Eg: Addison disease.
 Diminished secretion of ACTH due to
Adenohypophyseal or Hypothalamic failure
 Congenital failure of Cortisol secretion due
to defects in the enzymes responsible for its
synthesis.

Addison’s disease :
• Chronic deficiency of both Mineralocorticoids
and Glucocorticoids due to destruction of
adrenal cortex.

Features :
Hypoglycemia, Hypovolemia, Hypotension.
Resistance to stress & infection
Disturbed electrolyte balance.
Sometimes Vitiligo, change in pigmentation of
skin.

Adrenal Medulla
Adrenal medulla:
Derived from embryonic neural crest
ectoderm (same tissue that produces the
sympathetic ganglia).
Controlled by preganglionic sympathetic
innervations
(is like a postganglionic neuron!)
Secretes adrenaline ( epinephrine >90%)
(also secretes norepenephrine <10%)

Actions :
1.Intracellular actions :
• Adrenaline & NA produce different effects
depending on type of Adrenergic receptors
alpha & beta.
Effector organ Receptor Response
1.Eyeradial muscle contraction
Ciliary muscle ß Relaxation.

2. Metabolic actions :
•Both stimulates Gluconeogenesis, Glycogenolysis,
Muscle Glycogenolysis i.e. Hyperglycemic.
Adrenaline is more potent than NA.
•Both are lipolytic . NA is more potent than
adrenaline.

3. On CVS :
•Both increase force & rate of contraction of heart.
•Increases myocardial excitability.
•NA produces vasoconstriction in most organs but
Adrenaline dilates blood vessels in skeletal muscles
& liver.

4. On Skeletal muscle :
•Adrenaline increases muscular blood flow.
•Increases force of contraction.

5. Other effects :
•Inhibits GI motor activity.
•Relaxation of bronchioles to improve gas exchange.
•Dilatation of pupils.
•Increases renin release from kidneys.
•Enhances thyroid hormone secretion.

Some Actions of Catecholamine Hormones

Regulation of Adrenomedullary secretion :

PHEOCHROMOCYTOMAS
• a tumor of chromaffin tissue that produces excessive
quantities of catecholamines
• It may be extra-adrenal pheochromocytomas of
sympathetic ganglia located primarily within the abdomen
and that secrete norepinephrine.
• Symptoms include:
– Main feature is hypertension
– diaphoresis,
– palpitations, and anxiety
– Increased metabolic rate
– hyperglycemia

pancreas
Located in the curve of duodenum
Has both Exocrine & Endocrine function
Secretes major hormones:
Insulin
Glucagon
Somatostatin
Pancreatic polypeptide
Four types of cells , ß, D, F cells.

 cells Glucagon
 ß cells  Insulin
 Delta cells  Somatostatin
 F or PP cells Pancreatic polypeptide

Insulin
•Polypeptide containing two chains ( &ß)
linked by disulfide bridges.
•A chain21aa’s & B chain 30aa’s.

Biosynthesis :
• Synthesized in ER of ß cells.
•Pre proinsulin Pro insulinInsulin

Tissues that require insulin for effective uptake of
glucose
• Adipose tissue
• Resting skeletal muscle?
• Liver
Tissues in which glucose uptake is not affected by
insulin
• Nervous tissue
• Kidney tubules
• Intestinal mucosa
• Red blood cells
• β-cells of pancreas

Mechanism of Insulin secretion

Insulin secretion :
Increased Decreased
glucose .
Proteins.
Keto acids , FFA.
K+, Ca++
Glucagon.
Gastric Inhibitory Peptide.
Secretin, Cholecystokinin.
Vagal activity, Ach.
Fasting
Exercise
Somatostatin.
 Leptin.
K+ depletion.
Insulin.

Insulin Receptor
• The portion of the insulin receptor that
faces externally has the hormone-binding
domain.
• The portion of the insulin receptor that
faces the cytosol has tyrosine kinase
activity.
• When occupied by insulin, the receptor
phosphorylates itself and other proteins.

Actions :
1.Metabolic actions : Carbohydrate metabolism
On liver On muscle On adipose
tissue
Promotes
glycogenesis &
glycolysis.
Inhibits
glycogenolysis &
gluconeogenesis
Stimulates
transport of glucose
into cells.
Stimulates
glycogenesis.
Increase muscle
blood flow
Stimulates
transport of glucose
into adipose tissue.
Glucose is
converted into
glycerophosphate
& fatty acids
(minor)

Fat metabolism :
On liver On muscle On adipose tissue
Lipogenic & Anti-
ketogenic.
Glucose converted
to fatty acids
Favours Cholesterol
synthesis
Decreases
Apolipoprotein-B
synthesis.
Suppresses
lipoprotein
lipase
Inhibits
lipolysis.
Inhibits FFA
uptake,
Oxidation.
Inhibits
Hormone
Sensitive Lipase.
Stimulates use
of keto acids
Promotes
deposition of fat
into adipose
tissue.

Protein metabolism :
•Anabolic hormone.
•Stimulates Na+dependent transport of
neutral aa’s across cell membrane in muscle.
•Increases gene transcription.
•Contributes to body growth by stimulating
synthesis of macromolecules in bone,
cartilage & stimulates transcription of growth
factors such as IGF-I

Insulin decreases: Triglyceride breakdown (lipolysis) in adipose tissue
by decreasing the activity of hormone-sensitive lipase.
This enzyme is activated by stress hormones (i.e., cortisol, growth
hormone, epinephrine, glucagon).

Insulin decreases: Triglyceride breakdown (lipolysis) in adipose tissue by
decreasing the activity of hormone-sensitive lipase. This enzyme is
activated by stress hormones (i.e., cortisol, growth hormone, epinephrine,
glucagon).
The Adipose Cell

Electrolyte metabolism :
•Stimulates uptake of K+, Po4
-, Mg++ by cells.
•Regulates K+ balance.
•Increases renal reabsorption of K+, Po4
-, Mg++.

2. On CNS :
Selected areas of brain (hypothalamus)
requires insulin.
Injection of insulin into cerebral ventricles
decreases food intake.
Continuous insulin excess increase body
wt.& adipose mass  increase leptin levels 
induces satiety.

3. On blood vessels :
 Overall vasodilator effect  mediated by
increase in NO synthesis.
4. Autocrine effects :
ß cells also possess insulin receptors.
Essential for development of normal size islets
and for glucose stimulated insulin release.

5. On Growth :
• Essential for growth of an animal as GH is.
•Insulin & GH acts synergistically to promote
growth, each performing a specific function.

Regulation of Insulin secretion
1. Substrate stimulation :by a feedback
relationship with exogenous nutrient supply.

2. Hormonal control :
 GI hormones  Glucagon, Secretin, CCK,
GIP,GLP-I.
 Glucagon.
 Growth hormone.
 Cortisol.
 Thyroid hormones.
 Human Placental Lactogen.

3. Electrolytes :
 K+ & Ca++.
 Mg++ has a modulatory effect.
4. Neural control :
 Parasympathetic Increases secretion.
 Sympathetic  Decreases secretion.

To windup Metabolic actions of insulin

Diabetes
mellitus
A clinical state which is associated
with flow of sugar in urine which is due
to deficiency of Insulin /unresponsive to
Insulin

Causes :
Insulin deficiency.
Increase in levels of antagonistic hormones
(GH, Glucagon, Catecholamines, Cortisol).
Hereditary, Age, Obesity

Signs & Symptoms :
•Hyperglycemia.
•Glycosuria.
•Polyuria.
•Polydipsia.
•Polyphagia.
•Dehydration.
•Loss of weight.
•Ketonuria.
•Poor resistance to infections.

glucagon
is a peptide hormone
secreted by the α-cells of the pancreatic
islets
 Promotes mobilization rather than storage
of fuels, especially glucose.
Has opposite action to insulin.

Actions :
Have no influence on glucose uptake by
peripheral tissues.
Increases glycogenolysis & gluconeogenesis
in liver.
Lipolytic & Ketogenic hormone.
Inhibits storage of Tg’s in liver.
Have calorigenic action.

Regulation of Glucagon secretion

Stimulators Inhibitors
Amino acids
(Glucogenic)
CCK, Gastrin
Cortisol
Exercise
Beta adrenergic
stimulators
Glucose
Somatostatin
Secretin
FFA, Ketones.
Insulin.
GABA
Alpha adrenergic
stimulators
Glucagon secretion

Other Hormones Involved In Energy Balance And
Appetite
Leptin:
 produced in adipose tissue
• decreases hypothalamic neuropeptide Y (NPY)….
Which is Potent activator of feeding (orexigenic)
• Leptin, inhibiting NPY synthesis promotes satiety
(anorexigenic)
• increases energy expenditure, in part by
increasing fatty acid oxidation, and it decreases fat
stores
• Lack of and/or resistance to leptin causes obesity

Other Hormones Involved In Energy Balance
And Appetite cont…
Adiponectin:
 produced in adipose tissue
 increases insulin sensitivity and tissue fat
oxidation
 Prevents obesity??????

Other Hormones Involved In Energy Balance And
Appetite cont…
Ghrelin:
 produced by stomach cells
• reduced in response to a meal and highest in the
fasting state
• activates hypothalamic NPY neurons…. potent
orexigenic hormone
• stimulates the release of growth hormone (GH)
• Ghrelin levels are decreased in obese individuals
• elevated by low calorie diets, strenuous exercise

Overall View of Glucose Counterregulation

A endocrine-mrmc-to be used.ppt

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