PANCREATIC HORMONES
Dr. Amel Eassawi
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OBJECTIVES
The student should be able to:
 Know the cell types associated with the endocrine pancreas.
 Discuss the biosynthesis and secretion of insulin by the pancreatic beta
cells.
 Describe the regulation of insulin secretion from the pancreatic beta cells.
 Describe the regulatory effects of insulin on the metabolism of
carbohydrates, fats and proteins.
 Discuss the regulation of glucagon synthesis and release from the
pancreatic alpha cells.
 Know the actions of glucagon at the target tissue.
 Describe the dynamic relationship between insulin and glucagon in terms
of fuel storage, fuel mobilization and overall carbohydrate homeostasis.
 Describe glucose counter regulatory mechanisms.
 Discuss type 1 and type 2 diabetes mellitus with respect to etiology,
symptoms, and treatment.
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METABOLIC FUEL IN THE BODY
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PATHWAYS OF FUEL METABOLISM
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METABOLIC FUEL IN THE BODY
• Food intake is intermittent – nutrients must be stored for use
between meals
– Excess circulating glucose
• Stored in liver and muscle as glycogen
• Once liver and muscle stores are “filled up”, additional
glucose is transformed into fatty acids and glycerol and
stored in adipose tissue
– Excess circulating fatty acids
• Become incorporated into triglycerides
– Excess circulating amino acids Converted to glucose and
fatty acids.
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ENERGY METABOLISM
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METABOLIC FUEL IN THE BODY
• Absorptive State
– Fed state
– Glucose is plentiful and serves as major
energy source
• Postabsorptive State
– Fasting state
– Endogenous energy stores are mobilized to
provide energy
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METABOLIC FUEL IN THE BODY
Roles of Key Tissues in Metabolic States:
• Liver
– Primary role in maintaining normal blood glucose levels
– Principal site for metabolic interconversions such as gluconeogenesis
• Adipose tissue
– Primary energy storage site
– Important in regulating fatty acid levels in the blood
• Muscle
– Primary site of amino acid storage
– Major energy user
• Brain
– Normally can only use glucose as an energy source
– Does not store glycogen
• Mandatory blood glucose levels be maintained
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Pancreas
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PANCREAS
•
•
Beta (B cells)
– 60-70% of islet cells
– Insulin
Alpha (A cells)
– 20 -25% of islet cells
– Glucagon
•
Delta (D cells)
– 10% of islet cells
– Somatostatin
•
F (PP) cells
– Approx 1% of islet cells
– Pancreatic polypeptide
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Factors Affecting Blood Glucose Levels
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INSULIN
• Insulin
– Anabolic hormone
– Promotes cellular uptake of glucose, fatty acids, and
amino acids and enhances their conversion into
glycogen, triglycerides, and proteins, respectively
• Lowers blood concentration of these small organic
molecules
– Secretion is increased during absorptive state
• Primary stimulus for secretion is increase in blood glucose
concentration
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INSULIN
Insulin Receptor:
•Membrane glycoproteins composed of 2 subunits
• sub unit has Tyrosine kinase activity
•Sequence of events:
 Binding of insulin to  site unit trigger the
autophosphorylation of tyrosine kinase of  sub
unit. Thus insulin exerts its biological action.
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STIMULATION OF INSULIN SECRETION
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INSULIN
Glucose Transporters Recruitment:
• Insulin increases glucose uptake in most of the
cells by GLUT4 ( glucose transporters)
• GLUT4 operates only after binding with
insuline.
• In insuline dependent cells GLUT4 are
retrieved from plasma membrane when
insulin secretion decreases
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INSULIN
Carbohydrate Metabolism:
Liver : Promotes glucose uptake & storage:
 Promote glycogenesis( synthesis of glycogen from glucose)
 Increases activity of Glycogen Synthetase
 Inhibits Glycogenolysis( breakdown of glycogen into glucose)
 Inactivates liver Phosphorylase thus in liver.
 Inhibits Gluconeogenesis by( Conversion of amino acids into
glucose)
 decreasing the activity of liver enzymes necessary for
gluconeogenesis.
 Increases activity of Glucokinase.
 This causes initial phosphorylation of glucose after it diffuses
into the cells.
Therefore net effect is
 To increase glycogen synthesis in liver.
 To decrease glucose in blood
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INSULIN
Muscle
–
–
It increases glucose entry by increasing
GLUT4.
– Increases storage of glycogen
– Adipose tissue
•
Promotes glucose entry [GLUT4.] which is then
used to form  glycerol phosphate.
•
This provides the glycerol which combines with
fatty acids to form triglycerides thus promoting
deposition of fat.
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ATP PRODUCTION
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PRODUCTION OF KETONE BODIES
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INSULIN
Tissue that do not depend on insulin for
glucose uptake
• Brain
• Working Muscles (Exercising Muscles)
• Liver
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INSULIN
Brain:
• Under physiologic conditions, glucose is a necessary fuel
• Does not synthesize glucose
• Cannot store more than a few minutes’ supply of glucose as
glycogen
• Facilitated diffusion of glucose from the blood to the brain is a
direct function of the arterial plasma glucose concentration
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INSULIN
Protein Metabolism:
Insulin decreases blood amino acid level &
stimulate protein synthesis.
 Promotes active transport of amino acids in
muscles and other tissues
 Stimulates protein synthesis in cell
 Inhibits protein breakdown
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INSULIN
Fat Metabolism:
• Decrease blood fatty acid level & promotes
Triglyceride storage
– Promotes entry of fatty acids into adipose tissue cells
– Promotes entry of glucose into adipose tissue cellsprecursors for fatty acids and glycerol, raw material
for synthesis of triglycerides
– Promotes synthesis of triglycerides from fatty acids
and glycerol
– Inhibits lipolysis hence release of fatty acids from
adipose tissue
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INSULIN
Glucose Metabolism
Fasting State
• Decline in glucose
utilization by muscle
and adipose tissue
• Increase in lipolysis and
ketogenesis
• Ketones become major
fuel source for the brain
Fed State
• Suppression of
endogenous glucose
production
• Increase in glucose
utilization by liver,
muscle and adipose
tissue
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INSULIN
• Other Effects of insuline
1. Helps in general growth along with other
hormones.
2. On electrolytes causes increased entry of K+
into cells thereby decreasing plasma K+ levels.
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Factors Controlling Insulin Secretion
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GLUCAGON
• Glucagon
– Mobilizes energy-rich molecules from storage sites
during post absorptive state
– Secreted in response to a direct effect of a fall in
blood glucose on pancreatic α cells
– Generally opposes actions of insulin
– Glucagon is the hormone of "starvation."
– It produces hyperglycemia
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Blood Glucose and the Pancreatic Hormones
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GLUCAGON ACTIVITY
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GLUCAGON
CARBOHYDRATE:
- Stimulates hepatic glycogenolysis.
- Increases gluconeogenesis.
FAT:
- Promotes fat breakdown and inhibits triglyceride synthesis
- Increase fatty acids and glycerol in blood
- used for gluconeogenesis
- Oxidation for energy (Ketogenesis)
PROTEIN:
- Inhibits protein synthesis (proteolytic Effects)
- Glycogenolytic, Gluconeogenic, Lipolytic, Ketogenic Hormone.
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Interaction of Glucagon and Insulin
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Counteracting action of insulin & glucagon during absorption of high protein
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Importance of Maintaining Blood Glucose Within the Normal Range
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SOMATOSTATIN
Released from pancreatic D cells in direct response to increase in
blood sugar and blood amino acids during absorption of a meal
• Inhibitory effect on both insulin and glucagon
• Decreases motility of stomach, duodenum and gallbladder
• Decreases secretion and absorption in the gastrointestinal
tract.
Therefore somatostatin:
1. Inhibits digetion and absorption of nutrients
2. Decreased utilization of absorbed nutrients by tissues
3. Extends the availability of nutrients for longer periods of
time
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REGULATION OF INSULIN AND GLUCAGON BY SOMATOSTATIN
Somatostatin inhibits the release of both insulin and glucagon
Its release, in turn, is stimulated by glucagon and inhibited by insulin
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DIABETES MELLITUS
• Most common of all endocrine disorders
• Prominent feature is elevated blood glucose
levels
– Urine acquires sweetness from excess blood glucose
that spills into urine
• Two major types
– Type I diabetes
• Characterized by lack of insulin secretion
– Type II diabetes
• Characterized by normal or even increased insulin secretion
but reduced sensitivity of insulin’s target cells
TYPE I DIABETES MELLITUS
JUVENILE ONSET (IDDM)
•
•
•
•
•
•
10 % of D.M Cases
No insulin
Autoimmune process- selective destruction of β-cells
Precise cause unknown
Genetic susceptibility
Environmental triggers
Treatment :
• Insulin
• Dietary control
• Exercise
Type II Diabetes Mellitus
Maturity onset (NIDDM)
• 90 % of cases
• Normal or increase insulin secretion
• Decrease sensitivity of target cells to insulin i.e. insulin
resistance
• Cause :
– Ultimate cause unknown
– Various Genetic & lifestyle factors
– Obesity is biggest risk factor ( 90% are obese)
TYPE II DIABETES MELLITUS
– Link between obesity and insulin resistance
• Adipokines secreted by adipose tissue modulate
response of target tissue o insulin
– Resistine( promotes resistance ), increases in
obesity
– adiponektin (increase insulin sensitivity) ,
decreases in obesity
• Increase FA can indirectly triggers the apoptosis ofβcells
Treatment :
• Dietary control
• Exercise
• Oral hypoglycemic agents
Acute Effects of Diabetes Mellitus
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Both insulin-dependent and insulin-independent glucose uptake is reduced in insulin
resistant tissues
Obesity aggravates the tissue resistance
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REFERENCES
• Human physiology by Lauralee Sherwood,
seventh edition
• Text book physiology by Guyton &Hall,11th
edition
• Text book of physiology by Linda .s
contanzo,third edition
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