THE

PANCREAS
Dr.H.Gusbakti, MSc,PKK,AIFM
Professor of Physiology
University Islamic North Sumatera

TYPES OF TISSUES
1.Acini secretes digestive juices
2.Islets of Langerhans- has 3 types of cells namely
a. Alpha cells 25% - secrete Glucagon
b.Beta cells 60% - secrete Insulin and Amylin
c. Delta cells 10% - secrete Somatostatin
d. F cells secrete pancreatic polypeptide

INSULIN ACTION

1. CARBOHYDRATE METABOLISM
ANTIGLUCONEOGENIC
Increases entry of glucose into skeletal muscle, cardiac
muscle, smooth muscles
Increases peripheral utilization of glucose
Increases glycolysis in liver, muscles, adipose tissue
Increases synthesis of glycogen

INSULIN ACTION

2. FAT METABOLISM
ANTILIPOLYTIC ACTION
Increases synthesis of FFA by stimulating lipoprotein lipase
Inhibits hormone sensitive lipase

INSULIN ACTION

2. FAT METABOLISM
ANTILIPOLYTIC ACTION
Increases synthesis of FFA by stimulating lipoprotein lipase
Inhibits hormone sensitive lipase
3. PROTEIN METABOLISM
ANABOLIC ACTION
Decreases protein breakdown
Increases protein synthesis in muscles

INSULIN MECHANISM

FACILITATED Diffusion by glucose transporters

Decrease cAMP formation by inhibiting the activity of adenyl
cyclase activity.

REGULATORY MECHANISM

FACTORS STIMULATING INSULIN

CARBOHYDRATE

Hyperglycemia
stimulation
Increased level
blood glucose

FAT

PROTEIN

NEURAL

HORMONAL

Ketoacids

Increased
amino acids

parasimpatis

Glucagon
,GH,
secretin,
gastrin

vagal

INSULIN Hormone Associated with

Energy Abundance
1.Effect on Carbohydrate Metabolism
A. Promotes Muscle Glucose Uptake and Metabolism
-Storage of Glycogen in Muscle
B. Promotes Liver Uptake, Storage and Use of Glucose
Mechanisms:
a. inactivates liver phosphorylase
b. causes enhanced uptake of glucose from the
blood by the liver cells (by increasing the
activity of the enzyme glucokinase

C. increases activity of enzyme glycogen synthase , that

promote glycogen synthesis
- Glucose is released from the liver between meals
Lack of insulin activates Phosphorylase , which
causes splitting of glycogen into glucose phosphate
- Insulin promotes Conversion of Excess Glucose into
fatty Acids and Inhibits Gluconeogenesis in the
liver

C. Lack of Effect of Insulin on Glucose Uptake and Usage

by the Brain

2. Effect on Fat Metabolism

A.Insulin promotes Fat Synthesis and Storage
- Storage of Fat n the Adipose Cells
a. insulin inhibits the action of hormone-sensitive
lipase
b. insulin promotes glucose transport through the cell
membrane into the fat cells

B. Insulin deficiency Causes Increase Metabolic Use of Fat

causing
a . Lipolysis of Storage Fat and Release of Free Fatty
Acids
b. Increase Plasma Cholesterol and Phospholipid
c. Excess Usage of Fats during Insulin Lack Causes
Ketosis and Acidosis

3. Effect of Insulin on Protein Metabolism

A. INSULIN PROMOTES PROTEIN Synthesis and Storage
a. stimulates transport of amino acids into the cells
(valine, leucine, isoleucine, tyrosine,
phenylalanine)
b. increases the translation of messenger RNA,
forming new proteins
c. increases the rate of transcription of DNA genetic
sequences in cell nuclei
d. inhibits catabolism of proteins
e. depresses the rate of gluconeogenesis

INSULIN PROMOTES PROTEIN FORMATION AND

PREVENTS DEGRADATION OF PROTEINS
B. Insulin Lack Causes Protein Depletion and Increased
Plasma Amino Acids
- protein wasting is one of the most serious of
all effects of severe diabetes mellitus
C. Insulin and Growth Hormone Interact Synergistically to
Promote Growth

MECHANISMS OF INSULIN
SECRETION

CONTROL OF INSULIN SECRETION

1. Increased Blood Glucose Stimulates Insulin secretion

2. Other Factors That Stimulate Insulin Secretion:

a. Amino Acid most potent are arginine and lysine
- potentiates strongly the glucose stimulus for insulin secretion
b. Gastrointestinal Hormones Gastrin, Secretin, cholecystokinin,
Gastric Inhibitory Peptide

c. Other Hormones- Glucagon, Growth Hormone,

Cortisol, Progesterone and Estrogen
d. Autonomic Nervous System
-Stimulation of the parasympathetic nerves to the pancreas can
increase insulin secretion

Role of Insulin in Switching Between Carbohydrate

and Lipid Metabolism

GLUCAGON a hormone secreted by the alpha cells of

the islets of Langerhans when blood glucose
concentration falls. Its important function is to increase
blood glucose concentration thus is also called the
Hyperglycemic Hormone.

GLUCAGON - ACTION
Causes increased level of blood glucose in case of
hypoglycemia

GLUCONEOGENIC GLYCOGENOLYTIC, LIPOLYTIC, KETOGENIC

HORMONE

Stimulates gluconeogenesis
Stimulates glycogenolysis
Stimulates breakdown of glycogen into glucose
LIPOLYTIC ACTION increase FFA into blood

GLUCAGON - REGULATION

Factors stimulating glucagon

I. Hypoglycemia
II. Increased amino acids in blood
III. Symapathetic stimulation
IV. GIT hormones -- Gastrin Secretin
Factors decreasing glucagon stimulation
I. Hyperglycemia
II. FFA
III. Insulin

Effects on Glucose
Metabolism
Major Effects
1. breakdown of liver glycogen (glycogenolysis)
2.increased gluconeogenesis in the liver

Other Effects (when conc. rises above maximum

normally found in the blood
1.activates adipose cell lipase- increasing fatty acids
available to the energy system of the body
2.inhibits storage of triglycerides in the liver
3. enhances the strength of the heart
4. increases blood flow in some tissues, esp. kidneys
5. enhances bile secretion
6. inhibits gastric acid secretion

Regulation of Glucagon Secretion

a. Increased Blood Glucose Inhibits Glucagon Secretion
-

the most potent factor that controls glucagon secretion

the effect of blood glucose conc. on glucagon
secretion is in exactly the opposite direction from
the effect of glucose on insulin secretion

b. Increased Blood Amino Acids Stimulate Glucagon

Secretion (especially alanine and arginine)

SOMATOSTATIN INHIBITS GLUCAGON

AND INSULIN SECRETION

Factors Related to Ingestion of Food Stimulate

Somatostatin Secretion:
1. Increased blood glucose
2. Increased amino acids
3. increased concentrations of GI hormones
4. increased fatty acids

Inhibitory Effects of Somatostatin:

1. Acts on the islets of Langerhans to depress the
secretion of insulin and glucagon
2. decreases the motility of the stomach, duodenum and
gallbladder

 The Principal Role of Somatostatin is to

extend the period of time over which the
food nutrients are assimilated into the
blood

SUMMAR Y OF BLOOD GLUCOSE REGULATION

Mechanisms:
1. The liver functions as an important blood glucose buffer
system
2. Both insulin and glucagon function as important
feedback control systems for maintaining a normal
glucose concentration
3. Severe hypoglycemia stimulates the sympathetic nervous
system
4. Growth hormone and cortisol are secreted in response to
prolonged hypoglycemia, decreasing the rate of glucose
utilization by most cells

Importance of Blood Glucose Regulation:

1. Glucose is the only nutrient that normally can be used
by the brain, retina and germinal epithelium of
the
gonads
2. Blood glucose should not too high (reasons)
a. glucose exert a large amount of osmotic pressure in
the ECF causing cellular dehydration
b. high levels of blood glucose concentration causes loss
of glucose in the urine
c. causing osmotic diuresis by the kidneys
d. long-term increase in blood glucose cause damage to
many tissues, esp. blood vessels. Vascular injury
leads to heart attack, stroke, end-stage renal
failure and blindness

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NOMAD:ENDOPHYSIOL:
THYROID PARA

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NOMAD:ENDOPHYSIOL:
THYROID PARA

DIABETES MELLITUS
It is a syndrome of impaired
carbohydrate, fat, and protein metabolism
caused by either insulin lack or decreased
sensitivity of the tissues to insulin

Types of Diabetes Mellitus:

1. Type 1 Diabetes- also called insulin-dependent diabetes
mellitus (IDDM), is caused by lack of insulin secretion.

2. Type II Diabetes also called non-insulin dependent diabetes

mellitus (NIDDM) , is caused by decreased sensitivity of
target tissues to insulin. This reduced sensitivity to
insulin is often referred to as insulin resistance

Type I Diabetes- Lack of Insulin

Production by Beta cells of the Pancreas
CAUSES:
1. Viral Infection or Autoimmune Disease may be
involved in the destruction of the beta cells
2. Heredity

Usual onset of Type I diabetes occurs at about 14

years of age thus is often called Juvenile diabetes
mellitus

Principal Sequelae:
1.

Increased blood glucose

2. Increased utilization of fats for energy and

for formation of cholesterol by the liver
3. Depletion of the bodys proteins

Blood Glucose Concentration Rises to Very

High Levels in Diabetes Mellitus
Increased Blood Glucose Causes Loss of Glucose in
the Urine
Increased Blood Glucose Causes Dehydration
Osmotic diuresis, polyuria, intracellular and
extracellular dehydration, inceased
thirst(polydipsia)

Chronic High Glucose Concentration

Causes Tissue Injury:
Blood vessels function abnormally resulting
to inadequate blood supply to tissues
leading to risk of heart attack, stroke, end- stage kidney
disease, retinopathy and blindness, and
ischemia and
gangrene of the legs

Damage to tissues causing peripheral neuropathy

(abnormal function of peripheral nerves, and
autonomic nervous system dysfunction

Hypertension (secondary to renal injury)

and arteriosclerosis (secondary to
abnormal lipid metabolism)

Diabetes Mellitus Causes Increase Utilization of Fats

and Metabolic Acidosis leading to coma and death
As a result the patient develops severe metabolic
acidosis leading to coma and death
-Arteriosclerosis increased deposition of cholesterol
in the arterial walls
- Kussmaul breathing - rapid and deep breathing
physiologic compensation in metabolic acidosis

Diabetes Causes Depletion of Bodys

proteins
rapid weight loss and asthenia (lack of
energy) despite of eating large amounts of food
(polyphagia)
-

Type II Diabetes Resistance to Metabolic

Effects of Insulin
-more common than type I to 90% of all cases of
diabetes
-Onset occurs after the age of 30, often between 50 t0 60
years
- referred to as Adult Onset Diabetes
- related mainly to the increasing prevalence of obesity,
the most important risk factor for type II diabetes
in children as well as adults
Obesity, Insulin Resistance and Metabolic
Syndrome Usually Precede Development of Type II
Diabetes

Features of Metabolic Syndrome

1.
2.
3.
4.

5.

Obesity, especially accumulation of

abdominal fat
Insulin resistance
Fasting hyperglycemia
Lipid abnormality such as increased
triglycerides and decreased blood high
density lipoprotein cholesterol
hypertension

Other Factors That cause Insulin

Resistance and Type II Diabetes
1.
2.

Polycystic Ovary Syndrome (PCOS)

Excess formation of glucocorticoids
(Cushing Syndrome) or growth hormone
(acromegaly)

Development of Type II Diabetes During

Prolonged Insulin Resistance

Physiologic Diagnosis of Diabetes

Mellitus
1. Urinary Glucose
2. Fasting Blood Glucose and Insulin Levels
- in the early fasting blood glucose level is
normally 80 to 90 mg/100 ml
-110 mg/100 ml to be the upper limit

FBS above this value indicates diabetes mellitus

- type I diabetes plasma insulin levels are
very low or undetectable during fasting and
after a meal
type II diabetes plasma insulin concentration
is higher than normal
3. Glucose Tolerance Test
4. Acetone breath

TREATMENT OF DIABETES:
A.Type I diabetes administer enough insulin
B. Type II diabetes
-dieting and exercise
-drugs

Insulinoma Hyperinsulinism
- occurs from an adenoma of an islet of Langerhans
- insulin shock and hypoglycemia
- as blood glucose level falls into the range of 50 to 70
mg/dl the CNS becomes excitable leading to
hallucinations, extreme nervousness, trembles
all over, breaks out in a sweat

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