The Endocrine Pancreas Flashcards
Anatomy of the pancreas
Pancreas nestles with stomach and the duodenum. Overlays aorta and vein. Has a head, body and tail.
pancreas develops embryologically as an outgrowth of the
foregut
exocrine function
- Digestive enzymes directly into the duodenum (99% exocrine tissue) o Alkaline secretions via the pancreatic duct to duodenum
endocrine function
- Hormone production and release (1% of endocrine tissue) - From islets of Langerhans
is the pancreas mainly exocrine or endocrine
99% exocrine
important polypeptide hormones secreted by the pancreas
- Insulin - Glucagon - Somatostatin - Pancreatic polypeptide - Ghrelin - Gastrin - Vasoactive intestinal peptide (VIP)
major cell types in islets
- Beta cells- insulin
- Alpha- glucagon
- Delta- somatostain
- PP cells- OO
- Epsilon cells- Ghrelin
- G cells – Gastrin
- VIP
which hormones regulate the metabolism of CHOs, proteins and fats
insulin (CHOs, proteins and lipids) and glucagon (CHO and lipids)
properties of insulin and glucagon
Water soluble hormone
o Carried dissolved in plasma- no special transport
o Short half life- 5 mins
o Interacts with cell surface receptors on target cells
insulin main action
lowers blood glucose and promotes energy storage
target tissue of insulin
liver, adipose and skeletal muscle
- increases uptake of glucose via insertion of GLUT4 channels
- also increases glycogen synthesis in the liver
is insulin anabolic or catabolic
anabolic
main action of glucagon
opposed insulin- raises blood glucose
- stimulates glycogenolysis
- stimulates glucosneogensis
- stimulates lipolysis
stimulates proteolysis
target tissue of glucagon
liver and adipose
is glucagon anabolic or catabolic
catabolic
when blood glucose of high after a meal
- high blood glcuose promotes release of insulin from Beta cells of the pancreas
- insulin stimulates glucose uptake from blood increasing uptake in muscle and fat
- insulin also stimulates the conversion of glucose to glycogen in the liver lowering blood glucose
when blood glucose of low during fasting
- blood glucose low stimulates the release of glucagon
- glucagon stimulates the breakdown of glycogen to glucose
- glucoseneogensis stimulates
- glycogensis inhibited
importance of plasma glucose
Brain uses glucose at fastest rate in body
- Sensitive to falls in glucose and rise (increase osmolarity- shrinking)
- Circulation glucose needs to be controlled
normal blood glucose
3.3-6 mmol/L
(after meal 7-8 mmol/L)
renal threshold (point at which the tissue in the kidneys cannot deal with the amount of glucose in the plasma (cant filter and reabsorb), so instead of absorbing all glucose, glucose will be excreted in the urine (glycosuria))
10mmol/L
in pregnant women and the elderly the renal threshold
increases
Insulins effect on CHO, lipid and protein metabolism
Carbohydrate metabolism
- Increase glucose transport across the cell membrane
- Increases glycolysis
- Stimulate glycogenesis
- Inhibits glycogenolysis breakdown
- Inhibits gluconeogenesis
Lipid metabolism- decrease lipolysis
Protein metabolism – decrease proteolysis
structure of insulin
big peptide with an alpha helix structure
51 aa
2 polypeptide chains
2 disulphide bridged= rigid structure
Insulin synthesis
- The single polypeptide preproinsulin is synthesised in the nucleus of β cells.
- A signal peptide on the preproinsulin directs the polypeptide chain to the rough endoplasmic reticulum.
- Preproinsulin is cleaved to proinsulin.
- The proinsulin is folded and the disulphide bridges are formed.
- Proinsulin is transported to the golgi apparatus where it is cleaved to produce insulin and C-peptide, which are both packaged into a secretory granule that then waits for a signal to be released.
C-protein
can be used to measure insulin
Insulin is then released from the pancreatic β-cells via the following pathway
- Food intake results in an increase in blood glucoseconcentration.
- Glucose diffuses into the pancreatic β cell via GLUT2transporters.
- The increase in intracellular glucose causes an increase in glycolysis and ATP production.
- The increase in ATP production increases the intracellular ATP:ADP ratio.
- The increased ATP:ADP ratio causes the ATP-dependant K+channels on the cell membrane to close.
- The closure of the K+ channels causes the membrane to depolarise.
- Voltage-gated Ca2+ channels on the cell membrane open, and there is a calcium influx into the cell.
- The increase in intracellular calcium causes secretory granules (insulin) to be released via exocytosis.
release of insulin increases the uptake of glucose into cells of target tissue (liver, adipose, skeletal muscle) via the
insertion of GLUT4 channels and increase in glycogen synthesis
GLUT 4
allows transport of glucose across the target cell membrane
insulin receptors
are dimers with two identical subunits, made of one α and one β chain connected by a disulphide bond.
The α chain is on the exterior of the cell membrane, and the β chain spans the membrane in a single segment.
overall insulin…
Increases number of GLUT4 receptors on adipose, skeletal muscle and liver increasing uptake of glucose
GLUT 2
acts as a glucose sensor on pancreatic cells
glucagon is the hormone that
opposes insulin- acting to raise glucose levels
main actions of glucagon
stimulates glycogenolysis (liver)
stimulates glucoseneogenesis
stimulates lipolysis and proteolysis
structure of glucagon
29 amino acid structure comprised of only a single polypeptide, meaning its synthesis is more simple than insulin’s
synthesis of glucagon
Synthesised in RER of alpha cells, packaged in golgli, marginalised at cell surface and wait for signal to exocytose (in response to low glucose levels)
when glucose is low
- Granules move to the cell surface
- Margination- movement of storage vesicle to cell surface
- Exocytosis- fusion of vesicle membrane with plasma membrane with the release of the vesicle content
clinically when is glucagon used
Glucagon in emergency medicine is used when a person with diabetes is experiencing hypoglycaemia and cannot take sugar orally
where is glucagon most active
int he liver
