ENDOCRINE FUNCTIONS

OF PANCREAS

Dr. Rubab Amjad

Department of
Physiology
FMHCMD
Islets of Langerhans
■ Performs the endocrine function of pancreas
■ Human pancreas contains about 1 to 2 million islets
■ Types of cells in Islet of Langerhans:
Insulin
■ Secreted by β – cells in islets of Langerhans
■ Polypeptide with 51 amino acids
■ Two amino acid chains --- α- chain of insulin contains 21 amino acids,
β- chain contains 30 amino acids. Both are linked with disulfide
bridges
■ Half life: 5 minutes
■ Degraded in liver and kidney by a cellular enzyme called insulin
protease
Synthesis of Insulin
■ Precursor of insulin ---- pre-pro-insulin
(formed by translation of mRNA in ribosomes
attached to endoplasmic reticulum)
■ Pre-pro-insulin moves into rough
endoplasmic reticulum and is converted into
pro-insulin +
■ Pro-insulin consists of one A chain, one B Endopeptidase
chain and one connecting peptide in
between called C peptide
■ In ER, because of activities of
endopeptidase, proinsulin is converted into
insulin and C-peptide. A and B chains are
linked with disulfide linkages
■ Insulin, C peptide and little amount of
proinsulin are packed into secretory granules
by Golgi apparatus
Storage of Insulin
■ It is accumulated and stored in cytoplasm of β – cells in the form of
secretory granules along with C peptide
■ It is release by β – cells when required
Actions of Insulin

■ On carbohydrate metabolism
■ On protein metabolism
■ On fat metabolism
■ On growth
On Carbohydrate On Protein On Fat On
Metabolism Metabolism Metabolism Growth
Insulin reduced blood glucose Insulin causes Stimulates Promotes
level by: conversion and synthesis and growth by:
storage of proteins by: storage of fat by:
1. Facilitating transport and 1. Facilitating 1. Promoting 1. Anabolic
uptake of glucose from blood transport of amino transport of excess action on
into the cells by increasing acids into cells from glucose into cells proteins
permeability of cell blood by increasing and facilitates
membrane to glucose permeability conversion of
glucose into fatty
acids ad
triglycerides
2. Increasing the peripheral 2. Facilitating 2. Facilitates 2. Protein-
utilization of glucose, synthesis and storage transport of fatty sparing
oxidized immediately of proteins acids into adipose effect
tissues
3. Increasing the storage of 3. Inhibiting cellular 3. Promoting
glucose by converting it into utilization of proteins storage of fat in
glycogen in liver and muscle adipose tissues
4. Inhibiting glycogenolysis 4. Preventing
(breakdown of glycogen into conversion of proteins
glucose in muscles and liver) into glucose
Glucagon
■ Secreted by α – cells in Islet of Langerhans
■ Also secreted by A cells of stomach and L cells of intestine
■ Polypeptide containing 29 amino acids
■ Half life: 3 to 6 minutes
■ 30% degraded in liver and 20% in kidney
■ 50% of circulating glucagon is degraded in blood itself by enzymes
such as serine and cysteine protease
Synthesis of Glucagon

■ It is synthesized from the pre-pro-hormone precursor called pre-pro-

glucagon in α- cells of islets of Langerhans
■ Pre-pro-glucagon is converted into pro-glucagon which give rise to
glucagon
 Actions of Glucagon
On Carbohydrate On Protein On Fat Other
Metabolism Metabolism Metabolism Actions
Increases blood glucose level by: Increase transport of Lipolytic and
amino acids into liver ketogenic actions
cells
1. Increasing glycogenolysis in The amino acids are 1. It increases 1. Inhibits
liver and releasing glucose in utilized for lipolysis by secretion of
from liver cells into blood gluconeogenesis increasing the gastric juice
release of free
fatty acids from
adipose tissue for
peripheral
utilization
2. Increasing gluconeogenesis in 2. The lipolytic 2. Increase
liver by: activity of the secretion
a. Activating enzymes, which glucagon, in turn of bile from
convert pyruvate into promotes liver
phosphoenol pyruvate ketogenesis
b. Increasing the transport of (formation of
amino acids into liver cells. ketone bodies) in
Regulation of Glucagon: Role of Blood Glucose Level

Blood Glucose level α – cells of islets of

decrease below Langerhans are More glucagon is
80mg/dL of blood stimulated released

Inhibiting
command
Glucagon, in turn
High concentration increase blood
of glucose in blood glucose level
Role of Amino Acids

Increase in Stimulates
amino acids in secretion of
blood glucagon

Glucagon in turn
converts amino
acids into
glucose
Other Factors
■ Factors which increase glucagon secretion:
– Exercise
– Stress
– Gastrin
– Cholecystokinin
– Cortisol
■ Factors which inhibit glucagon secretion:
– Somatostatin
– Insulin
– Free fatty acids
– ketones
Somatostatin
■ It is secreted by:
1. Hypothalamus
2. δ- cells/ D cells in islets of Langerhans of pancreas
3. D cells in stomach and upper part of small intestine
■ Somatostatin is polypeptide in nature
■ Synthesized in two forms:
1. Somatostatin-14 (with 14 amino acids)
2. Smatostatin-28 (with 28 amino acids)
■ Half life: 2 to 4 minutes
■ Degraded in liver and kidney
Synthesis:
■ It is synthesized from precursor: pro-somatostatin
■ Pro-somatostatin is converted mostly into somatostatin-14 in D cells
of islets in pancreas
■ However, in intestine, large amount of somatostatin-28 is produced
from pro-somatostatin
■ Somatostatin brings out its action through cyclic AMP
Actions of Somatostatin
■ Somatostatin acts within islets of Langerhans and inhibits β and α-
cells to inhibit the secretion of both glucagon and insulin
■ Decreases the motility of stomach, duodenum and gall bladder
■ Reduces the secretion of GI hormones: gastrin, CCK, GIP and VIP
■ Hypothalamic somatostatin inhibits the secretion of Growth hormone
and Thyroid stimulating hormone from anterior pituitary (that’s why
called growth-hormone inhibitory hormone)
Pancreatic Polypeptide
■ It is secreted by F cells or PP cells in islets of Langerhans of pancreas
■ It is found in small intestine
■ Polypeptide with 36 amino acids
■ Half life: 5 minutes
■ Synthesized from pre-pro-hormone precursor called pre-pro-
pancreatic polypeptide
■ Degraded and removed from circulation mainly in kidney
■ Exact physiological action is unknown but believed to increase the
secretion of glucagon from α-cells
 Applied Physiology
■ Hypoactivity ---- DIABETES MELLITUS
■ Diabetes mellitus is a metabolic disorder characterized by high blood
glucose levels associated with other manifestations
■ Diabetes means polyuria and mellitus means honey
■ In most cases diabetes mellitus develops due to deficiency of insulin
■ Classification of Diabetes Mellitus:
• Primary • Secondary Diabetes (due
Diabetes to damage or disease of
(unrelated to pancreas by another disease
another disease) or factor)
• Causes:
• Endocrine
disorders:
gigantism,
Type I Diabetes Type II Diabetes acromegaly
Mellitus Mellitus • Surgical removal of
pancreas
• Hepatitis C and
Type I Diabetes Mellitus
■ Is due to deficiency if insulin because of destruction of β- cells in islets
of Langerhans
■ May occur at any age of life
■ Insulin dependent diabetes mellitus (insulin is injected a
treatment)
■ Causes:
– Degeneration of β- cells in islets of Langerhans of pancreas
– Destruction of β- cells due to viral infections
– Congenital disorder of β- cells
– Destruction of β- cells during auto-immune diseases
Type II Diabetes Mellitus
■ Due to insulin resistance (failure of insulin receptors to give response to
insulin)
■ Body is unable to use insulin
■ 90% of patients have type II diabetes
■ Usually occur after 40 years of age
■ Mostly controlled by oral hypoglycemic drugs
■ Non- insulin dependent diabetes mellitus
■ Causes:
– Insulin receptors are less, absent or abnormal resulting in insulin
resistance
■ Common cause of insulin resistance are:
– Genetic disorders
– Lifestyle changes such as bad eating habits and physical inactivity
leading to obesity
Diagnostic Tests for Diabetes
Mellitus
■ Fasting blood glucose
■ Postprandial blood glucose
■ Glucose tolerance test
■ Glycosylated hemoglobin
Complications of Diabetes
Mellitus:
■ Cardiovascular complications:
– Hypertension
– Myocardial infarction
■ Degenerative changes in retina called diabetic retinopathy
■ Degenerative changes in kidney called diabetic nephropathy
■ Degeneration of autonomic and peripheral nerves called diabetic
neuropathy
Hyperactivity --- Hyperinsulinism
■ Hypersecretion of insulin
■ Occurs due to tumor of β-cells in islets of Langerhans
■ Signs and symptoms:
– Hypoglycemia: blood glucose level falls below 50mg/dL
– Manifestations of central nervous system: blood glucose
decreases leading to increase activity of neurons resulting in
nervousness and tremors all over the body and sweating
■ If not treated immediately, leads to clonic convulsions and
unconsciousness
■ Slowly, the convulsions cease and coma occurs due of damage of
neurons