The Endocrine System

Pankreas

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 Pancreas

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 Pancreas gland

▪ A triangular gland, which has both exocrine and

endocrine cells, located behind the stomach
▪ Acinar cells produce an enzyme-rich juice used for
digestion (exocrine product)
▪ Pancreatic islets (islets of Langerhans) produce
hormones (endocrine products)
▪ The islets contain two major cell types:
▪ Alpha () cells that produce glucagon
▪ Beta () cells that produce insulin
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 Pancreatic islet (Islet of Langerhans)

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Islets of Langerhans

• Islets are spread throughout the pancreas

• 4 cell types
- α cells secrete glucagon
(20%)
- β cells secrete insulin
(75%)
-  cells secrete
somatostatin (<5%)
- F or PP cells secrete
pancreatic polypeptide
(rare)
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Department of Physiology Diponegoro University Faculty of Medicine
 Hormones of pancreas islets

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 Insulin

▪ A 51-amino-acid protein consisting of two amino

acid chains linked by disulfide bonds
▪ Synthesized as part of proinsulin and then excised
by enzymes, releasing functional insulin
▪ Insulin:
▪ Lowers blood glucose levels
▪ Enhances transport of glucose into body cells
▪ Counters metabolic activity that would enhance
blood glucose levels
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 Effects of Insulin Binding

▪ The insulin receptor is a tyrosine kinase enzyme

▪ After glucose enters a cell, insulin binding triggers
enzymatic activity that:
▪ Catalyzes the oxidation of glucose for ATP
production
▪ Polymerizes glucose to form glycogen
▪ Converts glucose to fat (particularly in adipose
tissue)

Department of Physiology Diponegoro University Faculty of Medicine

 Insulin secretion Physiological
by β cells Actions of
Insulin
• Increases uptake and
storage of glucose

• Stimulates glycogenesis

• Inhibits lypolysis,
promotes fat uptake and
storage

• Increases protein
synthesis
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 Physiological Actions of Insulin
Acts on tissues (especially liver, skeletal muscle, adipose) to
increase uptake of glucose and amino acids.
▪ without insulin, most tissues do not take in glucose and amino
acids well (except brain).
Increases glycogen production (glucose storage) in the liver and
muscle.
Stimulates lipid synthesis from free fatty acids and triglycerides in
adipose tissue.
Stimulates potassium uptake by cells (role in potassium
homeostasis).
Increased activity of glucose transporters: moves glucose into cells
Activation of glycogen synthetase: glucose  glycogen.
Inhibition of phosphoenolpyruvate carboxykinase. Inhibits
gluconeogenesis
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 Intracelullar insulin mechanism

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 Glucose uptake by insulin

Department of Physiology Diponegoro University Faculty of Medicine

 Regulation of Insulin Secretion

• Primary determinant = plasma glucose level

• Increased plasma amino acids

• Release of gastrointestinal hormones (GIP)

• Parasympathetic stimulation

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 Regulation of Blood Glucose Levels

▪ The
hyperglycemic
effects of
glucagon and
the
hypoglycemic
effects of
insulin

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 Insulin: Summary and Control Reflex Loop

Fed-state
Departmentmetabolism
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Department of Physiology Diponegoro University Faculty of Medicine
Regulation of insulin secretion

Department of Physiology Diponegoro University Faculty of Medicine

 Actions of insulin on liver

Department of Physiology Diponegoro University Faculty of Medicine

 Actions of insulin on muscle

Department of Physiology Diponegoro University Faculty of Medicine

 Effect of pancreas removal on blood glucose, plasma
free fatty acid and acetoacetic acid

Department of Physiology Diponegoro University Faculty of Medicine

 Glucagon

▪ A 29-amino-acid polypeptide hormone that is a

potent hyperglycemic agent
▪ Its major target is the liver, where it promotes:
▪ Glycogenolysis – the breakdown of glycogen to
glucose
▪ Gluconeogenesis – synthesis of glucose from lactic
acid and noncarbohydrates
▪ Release of glucose to the blood from liver cells

Department of Physiology Diponegoro University Faculty of Medicine

 Physiological Regulation
Actions of of Glucagon
Glucagon Secretion
• Increased by decreased
• Glycogenolysis plasma glucose
• Glyconeogenesis
• Increased by elevated
• Lipolytic plasma amino acids
• Ketogenic
• Increased by exercise

• Pancreatic sympathetic
stimulation

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 Regulation of Glucagon secretion

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Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
 Diabetes Mellitus (DM)
▪ Most common endocrine disorder
▪ Primary cause  reduced entry of glucose into
peripheral tissues
▪ Results from hyposecretion or hypoactivity of insulin
▪ Characterized by polyuria, polydipsia, weight loss
despite polyphagia, hyperglycemia, glucosuria, ketosis,
acidosis
▪ The three cardinal signs of DM:
▪ Polyuria – huge urine output
▪ Polydipsia – excessive thirst
▪ Polyphagia – excessive hunger and food consumption

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 Diabetes Mellitus (DM)

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 Insulin Dependent Diabetes Mellitus (IDDM)

• Also called type I or juvenile onset

• Associated with ketosis and acidosis

• Pathological changes in beta cells

• Plasma insulin low or undetectable

• Treatment  insulin injection

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 Pathophysiology of ketosis

• Diabetes mellitus is a state akin to starvation.

• There is plenty of circulating glucose, but since there is a
lack of insulin, the circulating glucose cannot be taken into
the cell to be utilised  increased lipolysis and increased
FFA production.
• Ketone bodies represent readily transportable fatty acids
that can be utilised by organs such as the heart and brain.
When there is a lack of glucose, improper utilisation of
components of the citric acid cycle leads to a continued
build up of ketones metabolic acidosis.
• The three ketone bodies: acetone, acetoacetate and  -
hydroxybutyrate.

Department of Physiology Diponegoro University Faculty of Medicine

 Non-Insulin Dependent Diabetes Mellitus (NIDDM)

• Also called type II or adult onset

• Patients are generally obese

• Insulin levels can be normal

• Insulin receptors downregulated

• Treatment  diet, sulfonylureas

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 Glucose Tolerance Test

• Administer a glucose challenge and monitor blood

glucose levels
• Blood glucose rises higher and returns to baseline
more slowly in diabetics

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 Glucose tolerance test on normal and DM people

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 Insulin Shock

• Insulin excess causes hypoglycemia

• Lack of fuel (glucose) for brain results in coma
• Hypoglycemia normally triggers secretion of:
– Glucagon
– Epinephrine
– Cortisol
– Growth hormone

Department of Physiology Diponegoro University Faculty of Medicine