Physiology Of The Endocrine Pancreas

Question 1

Major hormones secreted by the endocrine pancreas

Answer 1

B cells (70%)

• secretes insulin and amylin
• decreases gluconeogenesis/glycogenolysis/FA breakdown and ketogenesis
• increases glycogenesis, protein synthesis and glucose uptake
• amylin = suppress glucagon, slows down gastric emptying and promotes satiety

A cells (20%)

• secretes glucagon
• induces hepatic glycogenolysis and gluconeogenesis

D cells (2%)

• secretes somatostatin
• inhibits secretion and action of all pancreatic and gut peptides as well as growth hormone

PP cells

• secretes pancreatic polypeptide
• inhibits pancreatic exocrine secretion and facilitates hepatic action of insulin

E cells

• secretes ghrelin
• decreases insulin secretion and action

L and K cells

• secretes incretins (GLP-1, GIP)
• function is to amplify first phase insulin secretion, slows down gastric emptying and suppresses glucagon

Question 2

How does glucose oral vs IV affect insulin levels?

Answer 2

Oral glucose increases insulin secretion more than IV glucose

Insulin increases glycogen, ATP by

• upregulated glycogen synthase to produce glycogen
• up-regulating hexokinase and glucokinase to produce G6P and F,26-BP
• upregulates PK/pyruvate kinase and PFK enyzymes to produce ATP

Question 3

Review synthesis of insulin molecule

Answer 3

1) transcription of mRNA from DNA occurs in the cytosol
2) ribosomes translate mRNA into preproinsulin molecules
3) preproinsulin molecules get cleaved into proinsuilin in the ER
4) proinsulin moves to the Golgi apparatus, and gets bound to converting enzymes for cleavage sites.
5) in secretory granules proinsuilin is cleaved into C peptide and insulin

Question 4

Review of how glucose molecules induce releasing of insulin in B-cells

Answer 4

1) glucose enters cell via the GLUT2 transporter in hyperglycemia conditions
2) glucose is metabolized into energy molecules which inhibts K/ATPase channels in B-cells
3) the inhibition of K/ATPase channels results in depolarization of the cell as Vm becomes more positive
4) the depolarization opens voltage-gated Ca+ channels in plasma membrane Which further compounds calcium induced calcium release from sarcoplasmic reticulum in cells
5) elevated calcium leads to exocytosis of insulin containing secretory granules

in addition to glucose, CCK, B-adrenergics and acetylcholine can act via the Gq-IP3/DAG pathway to upregulate PKA and induce insulin release without calcium

somatostain acts on GI receptors to inhibit all of this

Question 5

B-adrenergic vs a-adrenergic stimulation on B-cells in pancreas

Answer 5

B-adrenergic
- increases insulin secretion

A-adrenergic

• decreases insulin secretion
• ** because sympathetic neurons to the pancreas release NE, and NE stimulates 1-adrenergic more, sympathetic activity inhibits insulin release**

Question 6

Blood concentrations that increases insulin release

Answer 6

Glucose concentration increased

Amino acid concentration increased

FFA’s increased

Ketones increased

Question 7

Hormone factors and other factors that increase insulin secretion

Answer 7

Hormones = GIP, glucagon, cortisol

Other factors = potassium, ACh, use of sulfonylurea drugs, obesity

Question 8

Major actions of insulin

Answer 8

Increases glucose uptake
Increases glycogen
Increases protein synthesis (anabolic)
Increases fat deposition and synthesis (VLDL and TAG)
Increases potassium uptake in cells (hypokalemia)

Decreases gluconeogenesis
Decreases glycogenolysis
Decreases lipolysis

Question 9

Factors that promote intracellular shift of potassium (hypokalmeia)

Answer 9

Insulin

Aldosterone

B-adrenergic stimulation

Alkalosis

Question 10

Factors that promote an extracellular shift of potasssium (hyperkalemia)

Answer 10

Insulin deficiency

Aldosterone deficency (Addison)

B-blockers

Acidosis

Cell lysis (tumor lysis syndrome or rhabdomyolysis)

Strenuous exercise

Increased extracellular osmolarity

Question 11

Factors that promote glucagon secretion

Answer 11

Fasting

Decreased glucose concentration

Increased amino acid concentration In blood (especially arginine)

CCK release in blood

B-adrenergic agonists

ACh release

Question 12

What is the insulin receptor

Answer 12

A tyrosine kinase that is a heterodimer of a/b subunits

• b subunit is the tyrosine kinase
• a subunit contains mass amounts of cysteine AAs also

When bound to insulin, auto phosphorylates itself and leads to downstream signaling which ultimately upregulates GLUT4 receptor deposition

Question 13

How does insulin deficiency lead to ketosis

Answer 13

Low insulin and high glucagon/pseudostarvation mood of the cells (cell think they are starving) results in increased lipolysis.

Increased lipolysis and FFAs get taken into the liver and are converted to ketoacids (especially B-hydroxybutyric acid and acetoacetic)

Question 14

How does osmotic diuresis lead to orthostatic hypotension

Answer 14

Osmotic diuresis results in a decrease in extracellular sodium and water

This results in decreased blood volume which leads to a decrease in venous return (frank starling mechanisms) and decreased arterial pressure
- results in pooling of blood in veins and hypotension

Standing up results in even further pooling due to gravity which causes the orthostatic hypotension

Question 15

Why cant insulin be taken orally?

Answer 15

It’s a peptide protien which means it will be degraded by gastric enzymes and proteases if swallowed