Pancreas

Is the overall effect of glucagon anabolic or catabolic?

Catabolic.

What is the main function of the exocrine pancreas?

Secreting enzymes and HCO3-.

What are the two main components pancreatic juices?

HCO3- and Enzymes.

Describe the function HCO3- in pancreatic juice

Neutralises stomach acid, protects the small intestine mucosa. Also provides the correct pH for digestive enzymes to function.

Describe the function enzymes in pancreatic juice

To digest the proteins, carbohydrates and fat in food material for absorption in the small intestine.

Why do horses and pigs produce substantial amounts of pancreatic juice?

They have a large large intestine for fermentation so the copious amounts of pancreatic juice create a suitable environment for fermentation.

What body fluid does pancreatic juice have a similar ion composition to?

Blood.

What ion is exchanged out of the duct lumen during HCO3- transport into the duct lumen

Cl-

Describe the movement of ions during HCO3- transport into the duct lumen

HCO3- is actively transported into the duct lumen in exchange for Cl-.

Water then follows by osmosis and H+ is correspondingly transported into the blood stream.

What is the significance of H+ moving into the blood stream during HCO3- transport into the gut lumen

This movement negates the alkaline tide.

Describe the absorption of HCO3- at normal flow rates

Reabsorbed into acinar cells.

Describe the absorption of HCO3- at high flow rates

Not enough time to reabsorb HCO3- so little is absorbed and hence the pancreas juice remains alkaline.

Describe the benefits of alkaline pancreatic juice at high flow rates

Prevents acidosis.

Describe the composition of Na+ and K+ in pancreatic juice

Always constant no matter the flow rate.

What enzymes does the pancreas secrete?

Trypsin(ogen), chymotrypsin(ogen), (pro)elastase, (pro)carboxypeptidase, lipase, phospholipase, amylase, ribo/deoxyribo-nuclease.

Why are proteases secreted in their inactive form?

Prevents auto-digestion.

What does amylose break starch down into?

Maltose.

What do lipases/phospholipidases break down fat into?

Glycerol and fatty acids.

What is the substrate for trypsin(ogen), chemotrypsin(ogen) and (pro)elastase?

Protein and peptides.

What is the substrate for (pro)carboxypeptidase?

Protein and peptides.

What is the substrate for lipase?

Triglycerides.

What is the substrate for phospholipase?

Phospholipids.

What is the substrate for amylase?

Polysaccharides.

What is the substrate for ribo/deoxyribonuclease?

RNA and DNA.

Describe the catalytic mechanism of trypsin(ogen), chemotrypsin(ogen) and (pro)elastase

Cleaves interior peptide bonds.

Describe the catalytic mechanism of (pro)carboxypeptidase

Release amino acids and carboxylic terminal.

Describe the catalytic mechanism of lipase

Cleaves ester bonds at 1- and 3- positions creating free fatty acids and monoglycerides.

Describe the catalytic mechanism of phospholipase

Cleaves ester bond at the 2- position.

Describe the catalytic mechanism of amylase

Cleaves starch and glycogen to maltose.

Describe the catalytic mechanism of ribo/deoxyribonuclease

Cleaves RNA and DNA into nucleotides.

Where are enteropeptidases found?

Duodenal epithelial surface.

What is the function of enteropeptidase?

Converts trypsinogen to trypsin.

State how trypsinogen can be converted to trypsin

Auto-catalysis and by enteropeptidases.

What do pancreatic cells do to prevent auto-digestion?

Secrete "trypsin inhibitors".

What are the 3 phases to pancreatic secretion?

cephalic phase, gastric phase, intestinal phase.

What are the cephalic and gastric phase mediated by?

Vagus nerve and gastrin.

In carnivores, what components are secreted at the gastric and cephalic phases of pancreatic secretion?

Only enzymatic components.

In the horse and the pig, what components are secreted at the gastric and cephalic phases of pancreatic secretion? And why?

Ionic components and enzymatic components so the chyme is more prepared for large intestine fermentation.

What is the intestinal phase mediated by?

Secretin and CCK.

Which hormone causes the largest increase in pancreatic secretion?

Cholecystokinin (CCK).

What hormone inhibits the effects of secretin?

Vasoactive inhibitory peptide.

What causes the release of secretin?

H+ levels in the duodenum.

What is the function of secretin?

Increase HCO3- secretion to neutralise acidic chyme.

Describe and state the feedback mechanism that secretin acts under

Negative feedback mechanism.

As acid chyme is gradually neutralised, the stimulus for secretin diminishes.

What causes the release of cholecystokinin (CCK)?

Fat and protein metabolites (e.g. fatty acids, monoglycerides, peptudes and amino acids).

What is the function of cholecystokinin?

Increase enzyme secretion from the pancreas, gall bladder contraction (if present).

Describe and state the feedback mechanism that cholecystokinin (CCK) acts under

Positive feedback mechanism.

Increased enzyme secretions produce more metabolites which in turn stimulate further CCK release. This terminates when metabolite levels deplete.

Describe the prevalence of pancreatic juice secretion in carnivores

Intermittent as there is intermittent flow of stomach contents into the small intestine.

Describe the prevalence of pancreatic juice secretion in ruminants

Continuous (irrespective of eating) as there is a continuous flow of rumen contents into the abomasum/small intestine.

Describe the prevalence of pancreatic juice secretion in horses

Continuous as there is a continuous flow of stomach contents into small intestine. However, secretions increase after feeding due to high amount large intestine fermentation.

Is the pancreatic juice in horses low or high in HCO3-?

Low.

How are horses able to neutralise acidic chyme?

Copious pancreatic secretions and secretion of HCO3- by the ileum.

What is the main function of the endocrine pancreas?

Regulation of metabolism.

What are the major types of cells within the islet of Langerhan?

α cells, β cells and δ cells.

Describe the proportion of the major cells in the islets of Langerhan

α cells ~ 65%

β cells ~ 25%

δ cells ~ 10%

Where are the Islets of Langerhans located?

In clusters scattered throughout the pancreas.

What proportion of the entire pancreas is the endocrine pancreas?

~ 1-2%.

Which cells in the Islets of Langerhans secrete Insulin?

β cells.

Which cells in the Islets of Langerhans secrete glucagon?

α cells.

Which cells in the Islets of Langerhans secrete somatostatin?

δ cells.

What is the function of somatostatin?

Inhibits both insulin and glucagon secretion.

Where are the hormones of the pancreas secreted into?

Hepatic vein.

What stimulates the release of insulin?

Increased plasma levels of glucose or plasma increase in amino acids, GI hormones (e.g. GIP).

Is the overall effect of insulin anabolic or catabolic?

Anabolic.

Describe the formation of insulin

Synthesised as a pro-hormone, converted to pro-insulin, secreted as active insulin by cleavage of the c-peptide.

What is the plasma half life of insulin

5-8 mins.

How is insulin deactivated?

In the liver by cleavage of disulphide bonds.

Describe the biphasic nature of insulin secretion

Initial immediate secretion of storage insulin lasting 5-15 mins. After this time period, it is followed by a more prolonged secretion of newly synthesised insulin adjusted to plasma levels of glucose.

Which causes greater insulin secretion - oral glucose or intravenous glucose?

Oral.

Describe the ANS regulation of insulin

Parasympathetic activity via vagus nerve is part of a long reflex arc that amplifies hormonal regulation.

Sympathetic activity and adrenaline release decreases insulin secretion.

What does the receptor for insulin function as upon activation?

Tyrosine kinase.

What is a tyrosine kinase?

An enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell.

What mediates the different actions of insulin within a cell?

Phosphorylation of intra-cellular proteins.

What does insulin stimulate during the absorptive phase?

Uptake of nutrients into the cell.

Which tissues are insulin dependant?

Nearly all tissues (especially skeletal muscle and adipose tissue).

Which tissues are insulin independant?

The brain, intestine, kidney and mammary tissue.

How is glucose uptake enhanced with insulin?

GLUT4 (glucose transport proteins) mobilise towards the cell membranes.

What enhances the uptake of amino acids?

Insulin - by amino acid transporter protein mobilisation.

Describe the effect of insulin on intracellular enzymes

Increases the concentration/activity of intracellular enzymes involved in the metabolism of glucose, amino acids and lipids. Also inhibits enzymes that break down triglycerides (e.g. hormone sensitive lipase).

What is the effect of glucose in the liver and skeletal muscle?

Increased glycogenesis.

What is glucagon released in response to?

Decreased plasma levels of amino acids or glucose but also increased plasma amino acids and increased sympathetic activity.

Describe the synthesis and secretion of glucagon

Synthesised as a pre-pro-hormone

Converted to pro-glucagon

Secreted as active glucagon

What is the plasma half life of glucagon?

5-6 minutes.

How is glucagon deactivated?

Metabolism in the liver or kidneys.

What enzyme does glucagon activate upon binding to a target cell receptor?

Adenylyl cyclase.

How is the net effect of metabolism of glucose determined?

Ratio of insulin to glucagon

How are plasma glucose levels increased by glucagon?

Stimulates liver glycogenolysis and gluconeogenesis.

Describe the tissues that glucagon effects c.f. with insulin

Glucagon has little effect on any tissues other than the liver where as insulin effects nearly all body tissues (especially skeletal muscle and adipose tissue).