Pancreas

 The pancreas is a glandular organ in

the upper abdomen.
 It serves as two glands in one: a
digestive exocrine gland and a hormone-
producing endocrine gland.
 Functioning as an exocrine gland, the
pancreas excretes enzymes to break
down the proteins, lipids, carbohydrates,
and nucleic acids in food.
 Endocrine pancreas
• Pancreas has two parts:
• The exocrine pancreas, which constitutes about
80% of the pancreatic tissue and controls digestion.
• The endocrine pancreas, which constitute 1-2% of
the pancreatic tissue and control storage and
utilization of the nutrients.
• Endocrine pancreas is imp endocrine organ as it
secretes insulin the only antidiabetogenic and
ketogenic hormone in the body.
• Pancreas secrete another three hormones:
glucagon, somatostatin and pancreatic
polypeptide.

• Insulin is anabolic and promotes storage of

nutrients(glucose, FA,AA).
• Glucagon is catabolic and promotes
mobilization of nutrients from their storage
depots into the blood stream.
• The endocrine pancreas constitute less than 2%
of total pancreatic tissue formed by islets of
Langerhans and each islets contains numerous
cells.
• Four types of cells present in islets.
• B cells :secrete insulin
• A cell : secrete glucagon
• D cell: secrete somatostatin
• F cell:secrete pancreatic polypeptide
 INSULIN
• Structure of insulin
Mechanism of insulin secretion
me
 Cont..
• Glucose enters through GLUT2 and is immediately
converted to glucose-6-phosphate(G-6P) by
glucokinase, which undergo metabolism to generate
ATP.
• ATP inhibits K+ efflux that causes depolarization of
the cell.
• Voltage gated Ca++ channels open and calcium influx
increases intracellular Ca++ conc.
• Calcium mediated exocytosis of insulin granules leads
to secretion of insulin.
 Mechanism of action
• Insulin acts on insulin receptors present on various
cells.
• The major target tissues of insulin are liver, skeletal
muscle and adipose tissues.

• Insulin receptor:
• It is a glycoprotein tetramer consist of two alpha and
two beta subunits.
• Alpha subunits is present on cell membrane
extracellularly, beta subunits is intacellular
• Alpha and beta subunits are linked by disulfide
bonds.
• Intracellular surface of beta subunits have
tyrosine kinase activity and on binding with
both subunits it gets autophosphorylated and
exert pysiological effects.
• Insulin binds to the α-subunit of its receptor, which
causes autophosphorylation of the β-subunit
receptor, which in turn induces tyrosine kinase
activity. The receptor tyrosine kinase activity begins a
cascade of cell phosphorylation that increases or
decreases the activity of enzymes, including insulin
receptor substrates, that mediate the effects on
glucose, fat, and protein metabolism. For example,
glucose transporters are moved to the cell
membrane to assist glucose entry into the cell.
 Physiological actions of insulin
• Insulin is secreted at fed state therefore, it is k/a hormone of
abundance.
• Insulin facilitates storage of nutrients when nutrients are
present in excess of energy need.
• It also suppresses mobilization of endogenous substrate.
• The stored nutrients are made available at the time of need
like ex, fasting.
• Insulin produce its target effects by acting mainly on liver,
adipose tissue, skeletal muscle.
• On carbohydrate metabolism
• On fat metabolism:
• Insulin increases storage of fat and inhibits
mobilization and oxidation of fatty acids from
fat depots.
• It decreases the level of FFA and ketoacids in
the plasma.
• Fat metabolism are achieved by its action on
adipose tissue and liver.
• In adipose tissue:
• by inhibiting lipolysis and decreases release of
stored FFA which in turn decreases formation of
ketoacids.
• Insulin facilitates use of ketoacids by peripheral
tissue.
• By promoting lipogenesis:
• Insulin promotes enzyme lipoprotein lipase and
makes FFA available from blood stream for
formation of triglyceride in adipose tissue.
• In liver: insulin is anti ketogenic and lipogenic In liver

• On protein metabolism: insulin is anabolic hormone

• It facilitates amino acid entry into muscle cell.so it
decreases plasma aminoacid conc.
• It promotes protein synthesis in ribosome ,achieved
by induction of gene transcription.
• Insulin also decreases degradation of RNA.
• Insulin inhibits proteolysis by decreasing lysosomal activity. Thus, it
decreases release of amino acid from muscle and inhibit their oxidation.
• Other action of insulin:
• Insulin decreases entry of phosphate and magnesium into
cell.
• It increases absorption of Na+, k+ phosphate from kidney.
• Insulin decreases food intake by inhibitory effect on
neuropeptide y released from hypothalamus.
• Insulin stimulates transcription of genes for growth factors
such as IGF-I &II.
 Diabetes mellitus
• Deficiency of insulin results in DM, most common
endocrine disorder.
• Causes:
• Diabetes occur due to destruction of beta cell of
pancreas. Or
• Due to decreased sensitivity of insulin receptors to
insulin.
Types:
Type I DM or insulin dependent (IDDM) as it is associated with
profound insulin deficiency and requires insulin replacement
therapy.

Type II DM or non-insulin dependent(NIDDM) as it is associated

with normal insulin level in plasma and patient is usually treaded
without insulin replacement therapy.

Gestation diabetes
• Type I DM: characterised by insulin
deficiency, caused by autoimmune destruction
of beta-cells of pancreas.
• Patients demonstrate antibodies against beta
cell surface antigens.
• This disease starts in childhood and
ketoacidosis is common.
• Type II DM: characterized by impaired ability
of target cell to respond to insulin.
• Usually caused by insulin receptor resistance.
Insulin secretion may be normal or even more.
• Disease starts late , in 3rd or 4th decade of life.
• Patients are overweight, sedentary in their
habits, chronic stress is also a factor.
• Usually complication is hyperosmolar coma.
• Oral antidiabetic drugs are usually prefered for treatment.

• Features:
• Glucosuria: loss of glucose in urine
• Polyuria: excess urine formation with increased frequency.
• Osmotic diuresis: excess glucose in renal tubules develops osmotic effect.
Osmotic effect decreases the reabsorption of water from renal tubules
resultin g in diuresis
• Polydipsia : increased water intake secondary to
polyuria
• Polyphagia: intake of excess food
• Asthenia :loss of strength because of protein
depletion caused by lack of insulin.
• Acidosis: due to insulin deficiency, glucose cannot be
utilized by peripheral tissues for energy, so it causes
breakdown of fat for energy which causes acidosis.
• Acetone breathing:in severe ketoacidosis,
acetone is expired in expiratory air giving
fruity odor.
• Circulatory shock: osmotic diuresis leads to
dehydration which can cause shock.
• Weight loss
• coma
Development of coma in diabetes
 Diagnosis of DM
• Fasting blood glucose
• Postprandial blood glucose
• Glucose tolerance test
• Glycated Hb