L5: Pancreas Structure and Function

What are the two pancreatic structures?

1. Acinar cells

2. Islets of Langerhans

what do acinar cells produce?

exocrine digestive enzymes

what do Islets of Langerhan cells produce?

endocrine hormones such as glucagon and insulin

Which cells in the pancreas produce insulin?

Beta cells of the Islets of Langerhans

Which cells in the pancreas produce glucagon?

Alpha cells of the Islets of Langerhans

Which cells in the pancreas produce somatostatin?

Delta cells

Which hormone is co-secreted with insulin and has its own endocrine activity?

Amylin.

What is the insulin precursor called?

Proinsulin

How are insulin and C-peptide produced from the precursor?

Proinsulin is cleaved to insulin and C-peptide

Where are insulin and C-peptide stored before release?

In secretory vesicles

Why is storage of insulin in vesicles important?

Enables quick release of insulin when needed

How is insulin primarily degraded?

Hepatic and renal enzymes

how do alpha and beta chains connect?

via sulfite bridges

what happens after the C chain is cleaved off the alpha and beta chain?

insulin and C-peptide will release

what is the advantage of having vesicle storage and release be quick compared to proteins?

protein synthesis takes a long time due to gene processing, so to make up for long time, peptides can be stored in vesicles for quick release when needed

What triggers insulin secretion in pancreatic beta cells?

Glucose metabolism increasing ATP production.

Which channels close in response to increased ATP during insulin secretion?

KATP channels.

What sequence follows KATP channel closure to release insulin?

1. Membrane depolarization (more + ions enter)

2. Ca2+ influx into cell

3. exocytosis of insulin-containing granules

Which ion influx is critical for insulin exocytosis?

Calcium (Ca2+) influx.

what does the exocytosis of insulin and C-peptide depend on?

glucose oxidation of beta cells to lead to a calcium influx

how is potassium retained in the cell after KATP channnels havel closed in the process of insulin secretion?

retained intracellularly

What is the main stimulus for insulin secretion?

Hyperglycemia (blood glucose > ~90 mg/dL)

what are other stimuli that increase insulin release besides hyperglycemia.

1. Elevated amino acids

2. incretins (GIP and GLP-1).

GIP

glucose dependent insulinotropic hormone

GLP-1

glucagon-like peptide-1

incretins

gastrointestinal hormones that respond to dietary carbohydrates and stimulate insulin release

What inhibits insulin secretion?

1. Hypoglycemia

2. epinephrine/norepinephrine

Which tissues are the main targets for insulin-dependent glucose uptake?

Muscle, adipose (fat), and liver.

what is the only tissue in the body that does not have an insulin receptor?

red blood cells

what are the other tissues besides muscles, fat, and liver that respond to insulin?

1. neurons

2. GI cells

3. renal cells

4. endothelium

5. leukocytes

what is the secondary messenger that is activated after ligand binding for insulin receptors?

tyrosine kinase will become phosphorylated

GLUTS

glucose transporters

what is the only GLUT not embedded in the cell membrane?

GLUT-4

what is the function of GLUTs?

to absorb glucose from circulation via facilitated diffusion

what controls GLUT-4?

insulin

where are GLUT-4 dominant in the body?

striated muscle and fat cells

how is GLUT-4 stored?

in intracellular vesicles

What happens to GLUT-4 transporters after insulin binds to its receptor?

GLUT-4 vesicles translocate to the cell membrane to enable glucose uptake.

glucose uptake into muscles and fat tissues can only occur …

in the presence of insulin (in hyperglycemia)

what does glucose uptake in muscle and fat do?

lowers blood glucose

what will happen to GLUT-4 if no insulin is present?

GLUT-4 will detach and enter storage; muscle and fat will have to use another energy source

How does insulin influence glucose uptake in muscle and fat?

It promotes uptake and utilization, lowering blood glucose.

MCQ: which two tissues are most dependent on insulin for their glucose uptake?

muscle and fat

how does insulin affect carbohydrate metabolism?

1. glucose uptake increases

2. glucose oxidation increase

3. glycogenesis increases

4. gluconeogenesis decreases

how does insulin affect lipid metabolism?

1. increase FFA uptake

2. increase lipogenesis from excess glucose

3. increase storage as triglycerides

4. decrease lipolysis

how does insulin affect protein metabolism?

1. increase amino acid uptake

2. increase protein synthesis

3. increase cell growth

4. decrease proteolysis

what processes are actively inhibited by insulin?

1. gluconeogeneis

2. lipolysis

3. proteolysis

what does insulin do to potassium?

moves potassium into cells

How does insulin affect potassium distribution?

1. stimulates Na-K-ATPase

2. inhibits K+ efflux (beta cells)

How can insulin deficiency or excess affect potassium homeostasis?

Both can disrupt K+ homeostasis (insulin excess can cause hypokalemia; deficiency can cause hyperkalemia risk).

Are insulin and C-peptide produced in equimolar amounts?

Yes.

What is one clinical use of C-peptide measurement?

Marker of endogenous insulin secretion.

c-peptide is a

bioactive molecule

what is the function of C-peptides?

1. increases blood flow by dilating blood vessels

2. facilitates neuron functions

insulin dependent patients benefit from replacement of…

insulin and c-peptide hormones

Where is glucagon produced?

In pancreatic alpha cells

what type of hormone is glucagon?

peptide

What stimulates glucagon secretion?

1. Hypoglycemia

2. sympathetic stimulation

3. high amino acid levels.

what is the mechanism for secreting glucagon?

1. low glucose uptake into alpha cell

2. low ATP levels

3. closure of ATP-sensitive K+ channels

4. depolarization

5. increase Ca2+ influx

6. exocytosis

what will happen to glucagon levels if glucose levels are low?

will increase

What inhibits glucagon secretion?

Hyperglycemia with concurrent insulin increase

what is glucagons target tissue?

mainly the liver

how does glucagon raise blood glucose levels?

1. glycogenesis

2. gluconeogenesis

What happens to glucagon when glycogen stores are depleted?

Gluconeogenesis becomes the dominant pathway for glucose production.

How do blood glucose and insulin levels affect glucagon levels?

Glucagon declines as blood glucose and insulin rise.

what are glucose levels in a hunger state?

decreased

what are insulin levels in a hunger state?

decreased

what are glucagon levels in a hunger state?

increased

what are glucose levels for a dog with normal pancreatic function, after eating a meal?

increased

what are insulin levels for a dog with normal pancreatic function, after eating a meal?

increased

what are glucagon levels for a dog with normal pancreatic function, after eating a meal?

decreased

what are glucose levels for a dog that does not produce adequate insulin levels, after eating a meal?

extremely increased

what are insulin levels for a dog that does not produce adequate insulin levels, after eating a meal?

decreased

what are glucagon levels for a dog that does not produce adequate insulin levels, after eating a meal?

decreased

Which hormones are released during nutrient absorption that modulate pancreatic secretions?

1. Somatostatin

2. amylin

3. pancreatic polypeptide.

somatostatin is derived from

delta cells

amylin is secreted with

insulin

What effects do somatostatin, amylin, and pancreatic polypeptide have on digestion and absorption?

1. Induce satiety

2. slow gastric emptying

3. reduce digestive enzyme secretion

4. reduce nutrient absorption

5. dampen glucose spikes.

What is the action of somatostatin on hormone secretion?

1. inhibits insulin, glucagon, and many other endocrines

2. can suppress functional tumors

How does amylin affect glucagon?

Amylin reduces glucagon secretion

How can amylin analogs be used clinically?

Therapeutically to reduce glucagon in diabetes management

What is the role of pancreatic polypeptide (PP) in insulin secretion?

1. PP reduces insulin secretion

2. PP analogs can be used to reduce functional tumors.

How are excess insulin and amylin related to pancreatic amyloidosis?

leads to pancreatic amyloidosis

pancreatic amylodosis

protein-misfolding disease with fibrils forming around pancreatic cells

what does pancreatic amyloidosis lead to?

progressive destruction of beta cells in pancreas

where is pancreatic amyloidosis seen?

feline DM type 2

what mostly causes amyloidoisis?

long-standing infections that increase in serum-amyloid-A NOT amylin

where are deposits in amyloidosis found?

1. kidney

2. liver

3. spleen

4. GIT

What is IAPP?

Islet Amyloid Polypeptide.

What are endocrinopathies in the context of the pancreas?

Hormone excess or hormone deficiency (absolute or relative) disorders.

What are the major pancreatic dysfunctions discussed?

Insulin excess and insulin deficiency.

what is the dysfunction of insulinoma?

1. increased glucose uptake and utilization

2. increased cellular K+ uptake

what are the effects on insulin excess?

1. hypoglycemia

2. hypokalemia

what are the CNS effects of insulin excess?

1. seizures

2. depression

3. lethargy

4. death

5. confusion

6. coma

what are the muscle effects of insulin excess?

1. muscle weakness

2. muscle atrophy

3. ventroflextion of neck

4. parylysis

5. paresis of hind limbs

what animal commonly suffers from insulin excess?

ferrets

what are the drugs used to treat insulin excess?

1. somatostatin analogs

2. diazoxide

how do somatostatin analogs work?

reduce insulin secretion

how does diazoxide work?

opens ATP-sensitive K+ channels to reduce insulin secretion