Pancreas Function and Diabetes
Glucose metabolism and absorption into the small intestine after we eat.
Glucose is a monosaccharide.
Glucose levels rise after we eat a meal.
Polysaccharides are digested to monosaccharides prior to absorption.
Different carbohydrates are broken down to different enzymes.
When broken down to glucose monomers it is absorbed by the small intestines by
cotransport with sodium ions
Sodium-dependent hexone: transporter that carries glucose to the enterocyte
(intestine cell wall)
Then it enters the bloodstream via GLUT2 by facilitated diffusion
How does the body respond to food?
Increased glucose levels occur when we eat.
Insulin is released when levels of blood glucose increase.
Glucose is then taken up into cells, so blood glucose levels decrease.
This occurs because the body uses glucose as a source of fuel.
Oral or IV glucose more effective
Oral glucose because it stimulates the release from the gut of incretin hormones.
This stimulates insulin secretion.
To increase glucose uptake into cells
What causes hypoglycaemia? 2 things
Too low blood glucose
Or excessive exogenous insulin
What are incretins?
group of hormones that regulate blood glucose.
these influence insulin secretion and glucose metabolism.
released from the GI tract.
in response to food intake
What are the two types of incretins? Where are they produced?
GIP
o Gastric inhibitory peptide
o Produced by K cells (found ion duodenum).
o It stimulates insulin release from pancreatic beta cells.
o In response to glucose in digested food.
o Promotes the storage of glucose into cells.
GLP-1
o Glucagon like peptide 1
o Produced by L cells in the small intestine and colon of enterocytes.
, o Stimulates insulin secretion from the pancreas in response to elevated blood
glucose levels.
o Promotes the uptake of glucose.
o Slows down gastric emptying.
o Suppresses glucagon release by alpha cells.
o The amount of these produced is proportional to the amount of food
consumed.
How does GIP and GLP-1 cause an insulinotropic effect? Where and how do they work?
Insulinotropic: stimulate insulin.
GIP
o Binds to GIPR
o Triggers increased intracellular cAMP and Ca2+ levels.
o In pancreatic beta cells.
o Causing insulin release.
GLP-1
o Binds to GLP-1R.
o This does the same as GIP.
Both inhibit gastric emptying and decrease food intake.
Inhibits glucagon secretion.
Slows the rate of endogenous glucose production.
How do we control the amount of insulin released via negative feedback in terms of GIP and
GLP-1?
GIP and GLP-1 are degraded quickly by DPP4 enzyme.
To prevent glucose levels becoming too low
How does the body respond to insulin?
Increases glucose uptake into muscle via GLUT4.
Increases glycogen synthesis.
Decreases gluconeogenesis in the liver.
Decreases glycogen breakdown.
Where in the body, what organs, does insulin effect?
Liver
Adipose
Muscle
Pancreas
Small intestine
How is insulin synthesised and then activated for use?
Glucose metabolism and absorption into the small intestine after we eat.
Glucose is a monosaccharide.
Glucose levels rise after we eat a meal.
Polysaccharides are digested to monosaccharides prior to absorption.
Different carbohydrates are broken down to different enzymes.
When broken down to glucose monomers it is absorbed by the small intestines by
cotransport with sodium ions
Sodium-dependent hexone: transporter that carries glucose to the enterocyte
(intestine cell wall)
Then it enters the bloodstream via GLUT2 by facilitated diffusion
How does the body respond to food?
Increased glucose levels occur when we eat.
Insulin is released when levels of blood glucose increase.
Glucose is then taken up into cells, so blood glucose levels decrease.
This occurs because the body uses glucose as a source of fuel.
Oral or IV glucose more effective
Oral glucose because it stimulates the release from the gut of incretin hormones.
This stimulates insulin secretion.
To increase glucose uptake into cells
What causes hypoglycaemia? 2 things
Too low blood glucose
Or excessive exogenous insulin
What are incretins?
group of hormones that regulate blood glucose.
these influence insulin secretion and glucose metabolism.
released from the GI tract.
in response to food intake
What are the two types of incretins? Where are they produced?
GIP
o Gastric inhibitory peptide
o Produced by K cells (found ion duodenum).
o It stimulates insulin release from pancreatic beta cells.
o In response to glucose in digested food.
o Promotes the storage of glucose into cells.
GLP-1
o Glucagon like peptide 1
o Produced by L cells in the small intestine and colon of enterocytes.
, o Stimulates insulin secretion from the pancreas in response to elevated blood
glucose levels.
o Promotes the uptake of glucose.
o Slows down gastric emptying.
o Suppresses glucagon release by alpha cells.
o The amount of these produced is proportional to the amount of food
consumed.
How does GIP and GLP-1 cause an insulinotropic effect? Where and how do they work?
Insulinotropic: stimulate insulin.
GIP
o Binds to GIPR
o Triggers increased intracellular cAMP and Ca2+ levels.
o In pancreatic beta cells.
o Causing insulin release.
GLP-1
o Binds to GLP-1R.
o This does the same as GIP.
Both inhibit gastric emptying and decrease food intake.
Inhibits glucagon secretion.
Slows the rate of endogenous glucose production.
How do we control the amount of insulin released via negative feedback in terms of GIP and
GLP-1?
GIP and GLP-1 are degraded quickly by DPP4 enzyme.
To prevent glucose levels becoming too low
How does the body respond to insulin?
Increases glucose uptake into muscle via GLUT4.
Increases glycogen synthesis.
Decreases gluconeogenesis in the liver.
Decreases glycogen breakdown.
Where in the body, what organs, does insulin effect?
Liver
Adipose
Muscle
Pancreas
Small intestine
How is insulin synthesised and then activated for use?
