ENDOCRINE SYSTEM
ASST. PROF. DR. EMRE HAMURTEKIN
EMU FACULTY OF PHARMACY
CHAPTER I
ENDOCRINE PANCREAS-LIVER and GH
ENDOCRINE PANCREAS
INTRODUCTION


Endocrine glands are highly vascularized clusters of
hormone-producing cells known as pancreatic islets
(islets of Langerhans).
Islets contain 4 principal endocrine cell types:
α-cells: glucagon (peripherally)
 β-cells: insulin (located centrally)
 δ- cells: somatostatin
 F-cells: pancreatic polypeptide



Sympathetic stimulation (α and β - adrenergic receptors):
increase energy substrate release into blood.
Parasympathetic stimulation (muscarinic receptors): stimulate
cells to take up and store energy substrates.
ISLET of LANGERHANS
GLUCAGON
GLUCAGON

FUNCTION:
1.
2.
3.
4.
Glycogenolysis
Gluconeogenesis
Lipolysis
Ketogenesis
1. Glycogenolysis:

Glucagon stimulates glycogen breakdown in liver, so
stimulates;
Glycogen phosphorylase
 Glucose 6-phosphatase

Liberates glucose for release into the blood circulation.
 Glucagon inhibits glycogen synthase enzyme.
 Glucagon also stimulates glycogenolysis in muscle to support
an increase in contractile activity.

Glycogenolysis
GLUCAGON
(+)
(+)
GLUCAGON
2. Gluconeogenesis:
 Glucagon
also stimulates glucose synthesis from noncarbohydrate sources (lipids and proteins) so it
stimulates;
 Glucose
6-phosphatase
 Fructose 1,6 bisphosphatase
 Glucagon
inhibits enzymes involved in glucose
breakdown like;
 Glucose
kinase
 Phosphofructokinase
 Pyruvate kinase
Gluconeogenesis
(-)
(+)
GLUCAGON
GLUCAGON
(+)
(-)
(-)
GLUCAGON
3. Lipolysis:
 Glucagon
causes the adipocytes to breakdown
triglycerides into glycerol and free fatty acids by
stimulating;
 Hormone-sensitive
lipase
4. Ketogenesis:
 Glucagon
stimulates the formation of ketone bodies
like;
 acetoacetate,
 β-hydroxybutyrate
 acetone
 Ketone
bodies are used in energy formation.
GLUCAGON

Increased secretion:
 CCK
 High
amino acid concentrations in blood
 Decreases in blood glucose (negative feed back)
 Sympathetic nervous system

Decreased secretion:
 Insulin
 Somatostatin
 Increases
in blood glucose, fatty acids and ketone
bodies (negative feed back)
 Glucagon-like peptide 1 (GLP-1)***
INSULIN
INSULIN
Major function is to lower the blood glucose
Uptake of glucose, fatty acids, glycerol,
ketone bodies and amino acids from the blood
INSULIN
BLOOD GLUCOSE and INSULIN SECRETION
insulin
*
** *
*
glutamate
CAC
INSULIN

FUNCTIONS:
1.
2.
3.
4.
5.
6.
Glucose uptake
Glycogenesis
Glycolysis
Lipogenesis
Inhibition in formation of the ketone bodies
Protein synthesis
Glucose Uptake
(+)
MUSCLE
INSULIN dependent
GLUT-4
(+)
ADIPOSE
LIVER
GLUT-4
GLUT-2
INSULIN dependent
Glycogenesis and Glycolysis
SKELETAL MUSCLE
Glucose
(+)
INSULIN
glucokinase
Glucose 6 - P
Glucose 1 - P
(+)
glycogen
synthase
Glycogen
(+)
Fructose 1,6 BP
Fructose 6 - P
PFK
(-)
glycogen
phosphorylase
Pyruvate
(+)
Pyruvate
dehydrogenase
Acetyl CoA
Glycogenesis and Glycolysis
LIVER
Glucose
(-)
(+)
INSULIN
Gluconeogenesis in hepatocytes
is inhibited
(-)
glucokinase
Glucose 6 - P
Fructose 6 - P
(+)
Fructose 1,6 BP
PFK
(-)
Glucose 1 - P
(+)
glycogen
synthase
Glycogen
PEP
(+)
(-)
glycogen
phosphorylase
(+)
Pyruvate
Pyruvate
dehydrogenase
Acetyl CoA
Other Effects of Insulin
(+)
lipoprotein lipase
FFA
TGs
INSULIN
(-)
hormone-sensitive
lipase
ADIPOCYTE


Insulin inhibits the ketone body formation and
secretion in hepatocytes.
In skeletal muscle and hepatocytes, insulin promotes
protein synthesis and inhibits protein catabolism.
Insulin Secretion

Insulin secretion is regulated by;



neural,
hormonal and
circulating substrate mechanisms.
Increases in blood glucose
Increases in fatty acids
Increases in amino acids
Glucagon
GLP-1
CCK
Acetylcholine
β – adrenergic stimulation
Decreases in blood glucose
Somatostatins
α – adrenergic stimulation
INSULIN
INSULIN
GROWTH HORMONE

GH is secreted from anterior pituitary gland (in reponse to GHRH from hypothalamus).

Secretion of GH is inhibited by somatostatin released from anterior pituitary gland.

A portion of GH binds to plasma proteins before biotransformation in liver.

Half-life of GH is short: ~ 25 min.
GH
GROWTH HORMONE
Collagen formation
and
condrocyte size and number
aa
aa
PROTEIN SYNTHESIS
GROWTH HORMONE
GH
Breakdown of TG
IMPORTANT
anti-insulin effect
Glucose uptake
GROWTH HORMONE


GH is released in pulses and is cyclic throughout the day.
FACTORS THAT INCREASE GH SECRETION:





Decreases in blood glucose
Decreases in blood fatty acids
Stress (physical or biochemical)
Sleep (related to growth and repair function)
FACTORS THAT DECREASE GH SECRETION:




Increases in blood glucose & fatty acids
Obesity
Aging
GH and IGF-1 (direct negative feedback)
Insulin-like Growth Factor 1






IGF-1 (somatomedin-C) is produced and secreted from
hepatocytes.
IGF-1 tightly binds to plasma proteins.
IGF-1 secretion is mediated by GH.
IGF-1mediates the actions of GH.
IGF-1 functions very similar to growth hormone (GH).
IGF-1 effects the musculoskeletal system by;
increasing amino acid and glucose uptake,
 increasing protein synthesis,
 increase in the breakdown of TGs in adipocytes


Increased IGF-1 correlates to growth in adolescence.
GH and IGF-1
GH DEFICIENCY
ACROMEGALY
• associated with excess GH secretion
• If epiphyseal plates haven’t closed yet, it leads to GIGANTISM
prominent brow
large hands / feet
large nose
prominent and large mandibula
COUNTER-INSULIN HORMONES
INSULIN
GLUCAGON
EPINEPHRINE
CORTISOL
GROWTH HORMONE
PROLACTIN
 Causes mammary glands growth
 Causes ductal proliferation
 Synthesis of breast milk
 Decreases sexual drive and reproductive
functions
PROLACTIN
 Tonic dopamine secretion from
hypothalamus suppresses prolactin
secretion.
 Prolactin secretion increases during
pregnancy.
 Nursing and breast manipulation
Increase prolactin secretion (sensory
input).
 Estrogen, Oxytocin, TRH and sleep
increase prolactin levels.
 Somatostatin and GH decrease
prolactin secretion.
OXYTOCIN
 Oxytocin has two primary functions in
female:
1. Contraction of myoepithelial cells in
breast tissue; allowing milk ejection
during lactation (milk letdown)
2. Contraction of uterine muscle during
parturition.
END of CHAPTER 1