The Endocrine Pancreas Flashcards
Describe the development of the gut
- Foregut: coeliac trunk
- Midgut: SMA
- Hindgut: IMA
- Pancreases is a large gland
- develops embryologically as an outgrowth of the foregut
What are the functions f the pancreas
• Pancreas has two functions – produces digestive enzymes secreted directly into duodenum (exocrine action) • Exocrine function forms the bulk of the gland – Alkaline secretions via pancreatic duct to duodenum – hormone production (endocrine action) • From Islets of Langerhans • ~ 1% endocrine tissue, 99% exocrine tissue
Describe the anatomy of the pancreas
Has a head, neck, body, tail, hits behind the stomach, head in duodenum, in front of aorta and portal vein
Foregut derivative
What are important polypeptide hormones secreted by the pancreas
• Important Polypeptide hormones secreted by pancreas - each secreted by a specified cell • Insulin - beta • Glucagon - alpha • Somatostatin - delta • Pancreatic polypeptide (PP) - pp cells • Ghrelin - e cells • Gastrin - g cells • Vasoactive intestinal peptide - vip cells
What are the major types of cell in the islets
– Beta ( β)-cells - Insulin – Alpha (α)-cell - Glucagon – Delta (d)-cells -Somatostatin – PP cells – e cells ghrelin – G cells gastrin – VIP - vasoactive intestinal peptide
The cell types in an islet all stain differently - see slide
Which hormonaes are involved in glucose regulation?
Insulin, glucagon
Describe the feedback look for plasma glucose regulation
High blood glucose islets are well perfumed with this plasma - this will stimulate the release of insulin from pancreatic beta cells. This will travel around target tissues and cause those cells to take up glucose - also stimulate the liver to produce glycogen - store. This will lower the plasma glucose levels.
Vice versa with fall- alpha - glucagon which works predominantly in liver
What are actions of insulin
Signal - feeding
Target tissues - liver (to make glycogen) adipose, skeletal muscle (take up glucose)
Affects metabolism - carbohydrates,lipids, proteins
Actions - anabolic
What are teh actions of glucagon
Signal - feeding
Target tissues - liver (break down glycogen), adipose (release sugars back into plasma)
Affects metabolism - carbs, lipids
Actions - catabolic
What is the importance of plasma glucose
• Brain uses glucose at fastest rate in body
– Relies on blood
• Sensitive to falls in glucose
• or rise = increased osmolarity
• Circulation glucose needs to be controlled
• Normally 3.3-6 mmol/L (UHL reference range)
• After a meal 7-8 mmol/L
• Renal threshold 10 mmol/L - the point at which glucose pass across filtrate in kidney and appear in urine - Elderly - higher renal threshold - longer time before it appears in urine
– Glycosuria
• Pregnancy renal threshold↓
• Elderly renal threshold↑
What are the properties of insulin and glucagon
• Water soluble hormones: – Carried dissolved in plasma – no special transport proteins – Short ½ life 5mins – interact with cell surface receptors on target cells – receptor with hormone bound can be internalised – inactivation
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What are properties on insulin
- Action (favours storage) it is the hormone of energy storage
- is anti-gluconeogenic – at high dosage lowers incorporation of pyruvate- into blood glucose, but also stimulated its incorporation into liver glycogen.
• Insulin is Anabolic
– anti-gluconeogenic
– anti-lipolytic and anti-
ketogenic
Describe this islats o langerhans
See slide
Why does the endocrine pancreas tissue have a good blood supply
Production of hormones - quickly taken up by blood supply and transported around
Describe the structure of insulin
• Insulin is a big peptide
with an alpha helix structure (3bits)
• consists of two un- branched peptide chains which are connected by 2 disulfide bridges this ensure stability (hold chains together)
– 51 amino acids
– 2 polypeptide chains
– (A = 21, B = 30)
– 2 disulphide bridges: = rigid structure
Outline the formation of insulin a
- Pre-proinsulin translation, signal cleavage, proinsulin folding
- Proinsulin is transported to Golgi
- Proinsulin is cleaved to produce insulin and C- peptide
See mcbg
In vesicle - marginate to surface - collect here
When there is a signal from influx of calcium - vesicles fuse with membrane - contents released
What transporter toes glucose enter through
GLUT2
Describe the action of KATP channels
Glucose closes K ATP channels in pancreatic beta cells - When glucose added - channel activity gone - no longer effluxing potassium - no longer hyperpolarised - now depolarised
Metabolic inhibition reopens K ATP channels - Hyperpolarisation - membrane potential closer to Ek
Cell-attached patch recordings, high external K -60mV
Makes the link between electrical excitability and metabolism. It cellis able to metabolise, it is able to make ATP, channels are inhibited in presence of ATP
Describe the release of insulin.
If metabolism is low, low atp, high adp, channels open, membrane hyperpolarised
When insulin perfumes cell eg after meal, glucose taken up through GLUT2, cell increase metabolic rate, produce ATP, inhibit K ATP channels, beta cell memb potential +ve - depolarise. On the cel surface there is a VOCC - depolarisation opens this - Ca2+ enters the cell down conc grads. Influx of Ca2+ triggers fusion of vesicles to B cell memb - release of insulin
What are the metabolic effects of insulin
• Insulin…. What does it do?
• increases glucose uptake into target cells and glycogen synthesis (insertion of Glut 4 channel - glucose enters target cells)
- no insulin - no signal - no glut 4 - no glucose uptake
– in the liver it increases glycogen synthesis by stimulating glycogen formation and by inhibiting
breakdown
– in muscles it increase uptake of AA promoting protein synthesis
– in liver inhibits breakdown of AA – in adipose tissue increases the storage of
triglycerides
• inhibits breakdown of fatty acids
Describe the insulin receptor.
– Insulin binds to the insulin receptor on cell surfaces
– receptor is a dimer
– two identical subunits spanning the cell membrane.
– two subunits are made of one α-chain and one β- chain, connected together by a single di-sulfide bond.
– α-chain on exterior of the cell membrane,
– β-chain spans the cell membrane in a single segment,
What is glucagon
• Hormone that opposes insulin – acts to raise blood glucose levels – It is glycogenolytic – gluconeogenic – lipolytic – ketogenic • it mobilizes energy release If patient has low levels of glucose - can give glucagon if unable to rally take it Normally would cause hyperglycaemia unless levels low
How is glucagon secreted
• Secreted by α- cells
• Secreted due to low glucose levels in α-cells
• Synthesized in Rough ER transported to Golgi - folded and a bit cleaved
• package in granules
• Effect mainly in the liver
• Granules move to cell surface
– Margination – movement of storage vesicles to cell
surface
– Exocytosis – fusion of vesicle membrane with plasma
membrane with the release of the vesicle contents.
C peptide MIGHT have a physiological effect - probably for a reason that affects smal vessels
