Download HORMONAL SECRETION OF PANCREAS (PANCREAS 1)

HORMONAL SECRETION OF PANCREAS
(PANCREAS 1)
LEARNING OBJECTIVE:
At the end of lecture student should be able to know:
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What is pancreas.
Endocrine and exocrine portion of pancreas,
Insulin secretion.
Insulin effects.
Diabetic mellitus
PANCREAS
 A triangular gland, A ions which
has both exocrine and
endocrine cells, located behind
the stomach.
 A dual organ having two
functions:
o Exocrine Functions.
o Endocrine Functions
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EXOCRINE FUNCTIONS:
o The exocrine function of the pancreas is localized in the
acinar cells.
o Acinar cells involves synthesis and secretion of digestive
juices – pancreatic juice.
o Plays an important role in
the digestion of proteins
and lipids.
o Has mild digestive action
on carbohydrates.
ENDOCRINE
FUNCTIONS:
o Performed by the islets of
Langerhans.
o Involves production of
hormones.
o Human pancreas contain 1 – 2 million islets.
ISLETS OF LANGERHANS
ORGAN SYSTEMS PANCREAS
 A triangular gland.
 There are two distinct within the pancreas
 The exocrine portion of the pancreas is made up of acini and
ductal systems.
ACINAR CELLS CONTAIN ZYMOGEN
ORGAN SYSTEMS PANCREAS
 The endocrine portion of the pancreas is served by
structures called the islet of Langerhans
o The islet of Langerhans have several
distinct cell types
 Alpha cells-produce
glucagon and constitute
approximate 25% of the
total islet cell number.
 Beta cells-the insulin
producing cells (majority of
the cells)
 Delta cells-produce
somatostatin
INSULIN
 Hormone of nutrient abundance
 A protein hormone consisting of two
amino acid chains linked by disulfide
bonds
 Synthesized as part of proinsulin (86 AA)
and then excised by enzymes, releasing functional insulin
(51 AA) and C peptide (29 AA).
 Insulin is secreted in response to high blood sugar, although
a low level of insulin is always secreted by the pancreas.
 After a meal, the amount of insulin secreted into the blood
increases as the blood glucose rises.
 Likewise, as blood glucose falls, insulin secretion by the
pancreatic islet beta cells decreases.
 In response to insulin, muscle cells,, and fat cells take
glucose in from the blood, which ultimately lowers the high
blood glucose levels back to the normal range.
 Insulin Structure
 Large polypeptide 51 AA (MW 6000)
 Tow chains linked by disulfide bonds.
 A chain (21 AA)
 B chain (30 AA)
 3 disulfide bonds.
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NORMAL INSULIN METABOLISM
Insulin is a peptide hormone composed of 51 aminoacids
that is synthesized, packaged and secreted in the pancreatic
beta cells.
The major regulator of insulin secretion is glucose which acts
both directly and by augmenting the action of other insulin
secretagogues.
A rise in the blood glucose levels, causes an immediate
release of insulin, presumably that is stored in the beta-cell
granules. If the secretory stimulus persists, a delayed
response follows, which involves active synthesis of insulin
from the beta-cells.
Other agents, including intestinal hormones and certain
aminoacids (leucine and arginine), as well as sulfonylureas,
stimulate insulin release.
INSULIN SYNTHESIS
 Insulin gene encodes a large precursor of insulin
(preproinsulin)
 During translation, the signal peptide is cleaved (proinsulin)
 During packaging in granules by Golgi, proinsulin is cleaved
into insulin and C peptide
Protein and Polypeptide Synthesis and Release
 Insulin synthesis is stimulated by glucose or feeding and
decreased by fasting.
 Threshold of glucose-stimulated insulin secretion is 100
mg/dl.
 Glucose rapidly increase the translation of the insulin mRNA
and slowly increases transcription of the insulin gene.
PROTEIN AND POLYPEPTIDE SYNTHESIS AND
RELEASE
INSULIN SYNTHESIS
LEVELS
 Blood glucose is normally maintained between 70 mg/dl and
110 mg/dl.
 Blood glucose levels below 70mg/dl, denote the situation of
"hypoglycemia".
 Although blood glucose levels of 110mg/dl can be normal,
this is only the case if a meal has been taken within 2 to 3
hours.
 A blood glucose level of 180mg/dl or more, is termed
"hyperglycemia.“
 Diagnosis is made if blood glucose levels are above
200mg/dl after drinking a sugar-water drink (glucose
tolerance test).
 Insulin excess causes hypoglycemia, which leads to
convulsions and coma.
 Insulin deficiency, either absolute or relative, causes
diabetes mellitus (chronic elevated blood glucose), a
complex and debilitating disease that if untreated is
eventually fatal
ISLETS OF LANGERHANS
 Islets of Langerhans consists of four types of cells :
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A cells or α cells
B cells or β cells
D cells or δ cells.
F cells or PP cells.
o Alpha cells - release the
hormone glucagon, which
o triggers the release of glycogen form liver stores and
o helps to raise the level of glucose (sugar) in the
o bloodstream.
o Beta cells - release the hormone insulin, which help regulate
carbohydrate metabolism into the bloodstream.
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FUNCTIONS OF INSULIN
Insulin is a major anabolic hormone. It is necessary for:
Transmembrane transport of glucose and aminoacids
Glycogen formation in the liver and skeletal muscles
Glucose conversion to triglycerides
Nucleic acid synthesis
Protein synthesis
Its principal metabolic function is to increase the rate of
glucose transport into certain cells in the body. These are
the striated muscle cells, including myocardial cells,
fibroblasts, and fat cells, representing collectively about 2/3
of the entire bodyweight.
GLUCOSE IS THE PRIMARY STIMULATOR OF INSULIN
SECRETION
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REGULATION OF INSULIN SECRETION
No insulin is produced when plasma glucose below 50 mg/dl
Half-maximal insulin response occurs at 150 mg/dl
A maximum insulin response occurs at 300 mg/dl
Insulin secretion is biphasic:
Upon glucose stimulation– an initial burst of secretion (5-15
min.)
Then a second phase of gradual increment that lasts as long
as blood glucose is high
INSULIN SECRETION IS BIPHASIC
INSULIN SIGNALING
INSULIN ACTION ON CELLS:
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INSULIN ACTION ON CARBOHYDRATE METABOLISM:
Liver:
Stimulates glucose oxidation
Promotes glucose storage as glycogen
Inhibits glycogenolysis
Inhibits gluconeogenesis
 Muscle:
 Stimulates glucose uptake (GLUT4)
 Promotes glucose storage as glycogen
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Insulin Action on Carbohydrate Metabolism
Adipose Tissue:
Stimulates glucose transport into adipocytes
Promotes the conversion of glucose into triglycerides and
fatty acids
GLUCOSE TRANSPORT
 GLUT2 (liver, pancreas)
 GLUT4, insulin sensitive transporter (muscle, adipose tissue)
 GLUT3 (brain)
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GLYCOGEN SYNTHESIS
Short term storage of glucose
Activates glycogen synthase
Inhibit glycogen phosphorylase
Glycolysis is also stimulated by insulin
Lipogenic and antilipolytic
Insulin promotes lipogenesis and inhibits lipolysis
Promotes formation of α-glycerol phosphate and fatty acid
synthesis
Stimulates fatty acid synthase (FAS)
Inhibits hormone sensitive lipase (HSL)
Activates lipoprotein lipase (LPL)
Protein Synthesis and Degradation
Insulin promotes protein accumulation:
Stimulates amino acid uptake
Increases the activity of protein synthesis
Inhibits protein degradation
ACTION OF INSULIN ON LIVER:
ACTION OF INSULIN ON FAT
ACTION OF INSULIN ON MUSCLE
INSULIN ACTION (SUMMARY):
 Dominates in Fed State Metabolism.
 glucose uptake in most cells
 glucose use & storage
 protein synthesis
 fat synthesis
DIABETES MELLITUS
DIABETES MELLITUS is a syndrome of impaired
carbohydrate, fat, and protein metabolism caused by either
lack of insulin secretion or decreased sensitivity of the
tissues to insulin.
TWO GENERAL TYPES:
o Type I diabetes, insulin-dependent diabetes mellitus
(IDDM):
 Caused by lack of insulin secretion.
o Type II diabetes, non–insulin-dependent diabetes
mellitus (NIDDM):
o Caused by decreased sensitivity of target tissues to the
metabolic effect of insulin. This reduced sensitivity to insulin
is often called insulin resistance.
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