Dr.

Farrukh Majeed
Department of Physiology
Endocrinology Lecture- 13

Endocrinal Pancreas lect-1-3

 Learning objectives
At the end of this lecture student should be able to:
• Determine hormonal regulation of blood glucose
• Describe Mechanism and control of Insulin secretion.
• Discuss functions of insulin on nutrients metabolism.
• Discuss the regulation and functions of glucagon.
• Describe role of Somatostatin in controlling Glucagon
and Insulin Secretion
• Analyze pathophysiology of type 1 and 2 Diabetes
mellitus
Hormonal regulation of blood glucose level

Thyroid Thyroid Circadian rhythm, cold Increase blood glucose

Hormone Gland concentration
 Insulin history
• In 1922 scientists Frederick Banting and Charles Best arrived
at a hospital ward for diabetic children, most of them
comatose and dying from diabetic keto-acidosis.
• This is known as one of medicine’s most incredible moments.
• Imagine a room full of parents sitting at the bedside waiting
for the inevitable death of their child.
• The scientists went from bed to bed and injected the children
with the new purified extract – insulin.
• As they began to inject the last comatose child, the first child
injected began to awaken. Then one by one, all the children
awoke from their diabetic comas.
• A room of death and gloom became a place of joy and hope.
 Physiologic Anatomy of the Pancreas
• The pancreas is composed of two major types
of tissues,
• the acini, secrete digestive juices into the
• the islets of Langerhans  secrete hormones
• The human pancreas has 1 to 2 million islets
of Langerhans, organized around small
capillaries.
• The islets contain three major types of cells,
• The beta cells 60 % of all the cells of the islets,
in the middle of each islet  insulin and
amylin
• alpha cells 25 %  glucagon
• delta cells 10 %  somatostatin
• PP cell, pancreatic polypeptide.
 Insulin Chemistry

• Insulin is a small protein;

• weight of 5808.
• It is composed of two amino acid
Chains connected to each other by
disulfide linkages.
• When the two amino acid chains are
split apart, the functional activity of
the insulin molecule is lost.
 Insulin synthesis
• Except for that portion of the
insulin that combines with
receptors in the target cells,
• the remainder is degraded by the
enzyme insulinase mainly in the
liver,
• to a lesser extent in the kidneys
and muscles,
• And slightly in most other
tissues.
Factors Increase or Decrease Insulin
Secretion
by Glucose
 Increased Blood Glucose Stimulates Insulin Secretion

• If the blood glucose concentration is suddenly

increased to a level two to three times normal
and kept at this, high level insulin secretion
increases markedly in two stages,
1. Plasma insulin concentration increases almost 10-
fold within 3 to 5 minutes from immediate release
of preformed insulin from the beta cells of the islets
of Langerhans. insulin concentration decreases in
another 5 to 10 minutes.
2. Beginning at about 15 minutes, insulin secretion
rises a second time and reaches a new plateau in 2 to
3 hours  rate of secretion even greater than that in
the initial phase. results from additional release of
preformed insulin and from activation of the enzyme
system that synthesizes and release new insulin from
the cells .
 Factors Increase or Decrease Insulin Secretion

• Amino acids  metabolized by the beta cells to increase

intracellular ATP levels  stimulate insulin secretion.
• Glucagon and gastric inhibitory peptide & acetylcholine 
increase intracellular calcium levels through other signaling
pathways in the presence of glucose  stimulate insulin
secretion
• Somatostatin and norepinephrine (by activating a-adrenergic
receptors) inhibit exocytosis of insulin.
• Sulfonylurea drugs bind to the ATP-sensitive potassium
channels stimulate insulin secretion
• parasympathetic activity in response to food in the digestive
tract  stimulates insulin
Insulin receptor action
Glucose transporters
 Skeletal muscle cells do not depend on insulin

• Skeletal muscle cells do not depend on insulin for

their glucose uptake during exercise, even though they
are dependent at rest.
• Muscle contraction triggers insertion of GLUT-4 into
the plasma membranes of exercising muscle cells in
the absence of insulin.
• Exercising muscle fibers become more permeable to
glucose
• This fact is important in managing diabetes mellitus
(insulin deficiency)
 Lack of Effect of Insulin on Glucose Uptake
and Usage by the Brain

• Insulin has little effect on uptake or use of glucose in the

brain.
• brain cells are permeable to glucose and can use glucose
without the intermediation of insulin.
• The brain cells are also quite different from most other cells of
the body in that they normally use only glucose for energy
and can use other energy substrates, such as fats, only with
difficulty.
• When the blood glucose falls too low, into the range of 20 to
50 mg/100 ml, symptoms of hypoglycemic shock develop,
characterized by progressive nervous irritability that leads to
fainting, seizures, and even coma.
Functions of Insulin
 Insulin: Metabolic functions
• Insulin lowers the blood levels of glucose,
fatty acids, and amino acids and promotes 
storage.
• As these nutrient molecules enter the blood
during the absorptive state, insulin 
promotes their cellular uptake  conversion
into glycogen, triglycerides, and protein,
respectively.
 Insulin: carbohydrate metabolism
Insulin is the only hormone capable of ↓ blood glucose.

1. Insulin facilitates glucose transport into most cells.

2. Insulin glycogenesis, the production of glycogen from glucose, in
both skeletal muscle and the liver. stimulates
3. Insulin inhibits glycogenolysis, the breakdown of glycogen into
glucose.
4. Insulin inhibits gluconeogenesis, the conversion of amino acids
into glucose in the liver. Insulin does so by decreasing the amount
of amino acids in the blood available to the liver for
gluconeogenesis and by inhibiting the hepatic enzymes required
for converting amino acids into glucose.
 Insulin: Fat metabolism
Insulin exerts multiple effects to lower blood fatty acids and
promote triglyceride storage:
1. It enhances entry of fatty acids from the blood into adipose tissue
cells.
2. Glucose serves as a precursor for formation of fatty acids and
glycerol, which are the raw materials for triglyceride synthesis.
3. It promotes chemical reactions that ultimately use fatty acids and
glucose derivatives for triglyceride synthesis.
4. It inhibits lipolysis, reducing the release of fatty acids from adipose
tissue into the blood.
Collectively, these actions favor removal of fatty acids and glucose
from the blood and promote their storage as triglycerides.
 Insulin: protein metabolism
Insulin lowers blood amino acid levels and enhances protein
synthesis through several effects:
1. It promotes active transport of amino acids from the blood
into muscles and other tissues. This effect decreases the
blood amino acid level and provides the building blocks for
protein synthesis within the cells.
2. It increases the rate of amino acid incorporation into protein
by stimulating the cells’ protein-synthesizing machinery.
3. It inhibits protein degradation.
The collective result of these actions is a protein anabolic
effect.  insulin is essential for normal growth.
 Reading material
• Guyton 11th edition, chapter 78, page 961-976.
• Sherwood 9th edition, page 685- 701
• https://steemit.com/science/@
towjam/one-of-medicines-most-incredible-moments-
insulin