study notes for lecture eight: pancreas

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8 Mar 2011
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\Æunqiue organ = has endocrine and exocrine portions
*Æwhen we discuss glucose metabolism and regulation, refer to pancreatic endocrine-made hormones
Q: which pancreatic hormone is anabolic, which is catabolic, which is negative?
Æinsulin is anabolic, favours energy storage
Æglucagon is catabolic, favours breakdown of energy storage to release nutrients (triglycerides Îfatty acids, glycogen Îglucose, protein ÎAAs)
Æsomatostatins are negative, they inhibit insulin and glucagon secretion
*metabolism = sum of all chemical reactions in the body
Æit is complex, stepwise and balanced
Æmost of the pathways are tightly regulated in a stepwise fashion so there are multiple intervention points
metabolic state I v. metabolic state II
Æfed Æfasted
Æabsorptive Æpost-absorptive
Æanabolic (glucose) Æcatabolic (glucose, fat)
*key hormone is insulin
*energy balance = control caloric intake and exercise
Æplasma glucose concentration is the most closely regulated of the three nutrient pools because glucose is the only fuel that the brain can
metabolize, except in times of starvation
carbohydrates fat protein
glycogen triglyceride muscle
liver, muscle adipose tissue
glucose fatty acid + glycerol amino acids
*glycogenolysis = breakdown of glycogen to glucose, stimulated under catabolic conditions
*glycogenesis = formation of glycogen from glucose
*gluconeogenesis = formation of glucose, takes place at the liver, increased in fasting conditions
*lipolysis = breakdown of fatty acids from triglycerides to fatty acids + glycerol {also blocked by insulin as it favours formation of storage
*lipogenesis = formation of lipids/triglycerides
Æpancreas is a gland organ in the digestive and endocrine system
Æendocrine gland produces several important hormones, including insulin, glucagon, and somatostatin,
\Æhormones are secreted directly into the bloodstream
\Æparacrines are hormones that are released that affect only target cells nearby the release site
Æexocrine gland, secretes pancreatic juice containing digestive enzymes that pass to the small intestine.
\Æenzymes are secreted into ducts that lead to the external environment
\Æthese enzymes help to further break down the carbohydrates, proteins, and fats in the chyme.
\Ærelease *zymogen ± inactive enzyme precursor that requires a biochemincal change to become active (change reveals active site or changes
conformation to reveal active site)
\Æzymogen is released to prevent the enzymes from digesting proteins in the cells in which they are synthesized
Æthe part of the pancreas with endocrine function is made up of ~1 million cell clusters ± islets of Langerhands
\Æislets of Langerhans consist of 4 main cell types classified by their secretion products
::alpha-cells secrete glucagon ::beta-cells secrete insulin ::delta-cells secrete somatostatin ::PP cells secrete pancreatic polypeptide
endocrine pancreas
Æregulator of metabolism
Æexocrine (acinar) cell
-cell .-cell /-cell
Æforms insulin from Æforms and Æforms and secretes
pro-insulin releases glucagon negative hormones: somatostatins
Æreleases C-peptide + active \Æhas paracine function to inhibit
insulin insulin release and glucagon function
insulin & glucagon signal target cells to change gears between feeding and fasting metabolism
- insulin binds to receptor on the surface of the cell
- binds to a tyrosine kinase receptor-enzyme
- binding results in activation of a 2nd messenger system ± intracellular
signalling cascade
- phosphorylation of proteins occurs during the signalling pathway
- leads to a cellular response
glucagon binds to receptor on the surface of the cell
binds to a G-protein coupled receptor
binding results in activation of a 2nd messenger system ± intracellular
signalling cascade
phosphorylation of proteins occurs during the signalling pathway
leads to a cellular response
- anabolic hormone
- dominant hormone
of fed state
- synthesized as a
typical peptide
- synthesized from
with a signal
- signal peptide
directs movement
of pre-pro-
hormone to
undergo proper
- pro-insulin is
cleaved for form
active insulin {A
and B chains} and
inactive C-peptide
- removal of signal
peptide sequence
increased glucose levels = primary
stimulus for insulin secretion
increased [glucose]blood results in
glucose to binding to GLUT transporter
on thHVXUIDFHRI-cells
increases glycolysis and citric acid
results in increased levels of ATP
products from glycolysis and citric acid
ATP closes the ATP-sensitive K+
channel (was previously open)
closed K+ channel results build up of
K+ in the cell
build up causes the cell to depolarize
depolarization of cell causes Ca2+
channel to open
free calcium flows into the cell via the
Ca2+ channel triggering exocytosis of
vesicles containing insulin
insulin is VHFUHWHGIURPWKH-cell
o binds to receptor tyrosine kinase
o reduces blood glucose levels
o in the fed state, insulin is the most potent
anabolic hormone known ± increases synthesis
the synthesis and storage of carbohydrates,
lipids and proteins, while inhibiting their
degradation and release to the blood
::favours glycogen formation
o insulin favours glucose uptake from
extracellular environment to the intracellular
environment by direct stimulation of GLUT-4
transporters on muscles and fat,
o in the liver, indirectly increases glucose uptake
as GLUT-2, found on the surface of liver cells,
is not directly stimulated by insulin
o insulin binds to tyrosine kinase receptor, results
in signal cascade, activating hexokinase
o results in hexokinase-mediated conversation of
intracellular glucose to glucose-6-phosphate
o this lowers [glucose]intracellular, favouring
glucose uptake from the extracellular
environment via GLUT-2 transporters
o eventually glycogen is made
Other Considerations
- from DNA, miRNA gene is transcribed to pre-miRNA
myotrophin mRNA is translated and
o microRNA (from DNA) in beta-