Pancreas Physiology - Trachte

Question 1

How much glycogen can we store?

Answer 1

Glycogen stores in liver and muscle = 500 grams (almost a pound) total body stores which can last ~ 12 h.

Question 2

How much Triglyceride can we store?

Answer 2

Triglyceride stores in adipose tissue are unlimited

Question 3

What happens to the excess glucose during the fed state?

Answer 3

Consume carbs => excess glucose, the two molecules of pyruvate produced during glycolysis are processed differently than they are during energy production.

They are converted to citrate within the mitochondria of liver and fat cells, and the citrate is subsequently used to manufacture fatty acids.

Fatty acids are then attached to glycerol to form triglycerides, which are your body’s primary form of fat storage.

Question 4

What energy stores are utilized when glucose intake is low?

Answer 4

**GLUCOSE is the preferred primary energy source for brain. Ketone bodies are the back-up energy source.

First: Glycogen breakdown in liver and muscle to produce glucose. Reserves depleted within 24h.

Next: Adipose triglycerides are catabolized to glycerol and free fatty acids: Glycerol can be made into glucose via gluconeogenesis in the liver. Free fatty acids, aceotacetate and beta hydroxybuterate, can be made in the liver. Ketone bodies are converted to acetyl CoA to produce energy in the citric acid cycle in other tissues including brain, muscle..

Eventually, muscle wasting: Proteins catabolized to amino acids. Amino acids can be made into glucose via gluconeogenesis in the liver.

Question 5

How does insulin inhibit lypolysis and promotes triglyceride storage?

Answer 5

Insulin inhibits breakdown of fat/adipose tissue by inhibiting intracellular lipases that hydrolyze triglycerides. (Net result is no release of fatty acids and glycercol)

Insulin promotes accumulation of triglyceride in fat cells by facilitating entry of glucose into adipocytes and liver

Liver derived Fatty acids are packaged as lipoproteins and secreted and in circulation become free fatty acids.

Adipose picks up FFAs which is used to make triglycerides (by combining with glycerol).

Question 6

Is insulin or glucagon anabolic/catabolic?

Answer 6

Insulin = anabolic

Glucagon = catabolic

Question 7

What are normal blood glucose levels? normal fasting? hyperglycemia? hypoglycemia?

Answer 7

Normal blood glucose = 70~120 mg/dL

Normal fasting ~130 mg/dL (~7 mM)

Hypoglycemia

Question 8

What cells secrete what hormones in the Islets of Langerhans?

Answer 8

Alpha = Glucagon

Beta = Insulin, amylin

Delta = Somatostatin

Epsilon = Ghrelin

Question 9

What happens when you deactivate the K+ channel?

Answer 9

Depolarization of cell

Question 10

What happens when you activate the K+ channel?

Answer 10

Hyperpolarization of cell

Question 11

What activates Pancreatic Beta-cells?

Answer 11

Glucose, amino acids, and ketoacids evoke insulin secretion. Primary stimulus is glucose.

Secretion is calcium dependent:
A rise in ATP, due to the metabolism of nutrients, closes an ATP-dependent K-channel => which DEPOLARIZES the cell. Extracellular calcium enters via a voltage-dependent Ca-channel and stimulates the secretion of insulin.

Question 12

What stimulates the intracellular release of calcium of Pancreatic Beta Cells?

Answer 12

Glucagon,GLP-1, GIP via adenylate cyclase (Gi-protein)

ACh and CCK via Phosholipase C

Question 13

What inhibits the intracellular release of calcium of Pancreatic Beta Cells?

Answer 13

Somatostatin, EPI, NE

Cholinergic stimulation increases and adrenergic stimulation decreases secretion of insulin

Question 14

What type of receptor is the Insulin receptor?

Answer 14

tyrosine kinase receptor

Question 15

What type of receptor is the Glucagon receptor?

Answer 15

G-protein coupled receptors

Question 16

What is Insulin composed of?

Answer 16

Proinsulin is 86 AA => Insulin 51 amino-acid acid mature polypeptide (alpha chain + beta chain) => C-Peptide (Connecting Peptide=C-Chain) connects alpha and beta chain of Insulin

C-peptide can be measured as an indicator of endogenous insulin production in diabetic patients

Question 17

How is glucagon synthesized?

Answer 17

Produced in a-cell of pancreas
Synthesized as proglucagon

Proglucagon gene is spliced into glucagon in pancreatic beta cells and into GLP-1 and GLP-2 in intestinal cells.

Question 18

What increases glucagon synthesis?

Answer 18

Increases with hypoglycemia, decreases with hyperglycemia

Increases with amino acids (to protect from hypoglycemia of an all protein meal).

Increases with Sympathetic (mobilizes in flight/fright) and Vagal stimulation (temper insulin effects)

Question 19

What three processes does glucagon promote?

Answer 19

Promotes liver gluconeogenesis

Promotes glycogenolysis

Promotes lipolysis

Question 20

What are the actions of Somatostatin after it is made by pancreatic Delta cells?

Answer 20

SST is triggered by increased insulin.

SST inhibits secretion of insulin, glucagon, ghrelin.

In the G.I., SST net result is to reduce the rate of food absorption.

SST is inhibited by ghrelin which is a general signal of hunger.

Question 21

What are “Incretins”?

Answer 21

GI hormones that are Mediators of Intestinal Phase of Insulin Secretion = GIP and GLP-1

Question 22

What is the action of GLP-1?

Answer 22

GLP-1 = glucagon like peptide 1

Stimulates insulin in high glucose situation (feeding)

Question 23

What is the action of GIP?

Answer 23

GIP = glucose dependent insulinotropic peptide

old name: gastric inhibitory peptide

promote beta cell insulin release after eating

Question 24

What are the phases of insulin secretion?

Answer 24

1. Cephalic Phase:
   Parasympathetic information from sight & smell
2. Oral Phase:
   Parasympathetic information
   Carbohydrate sugar stimulation of sweet receptors
3. G.I. Phase:
   The Incretins:
   GIP = the glucose-dependent insulinotropic peptide is a member of the secretin family of hormones.
   Produced in response to hyperosmolarity due to glucose in gut. The amount of insulin secreted is greater when glucose is administered orally than intravenously.
   GLP-1 = derived from proglucagon gene stimulates insulin
4. Blood Glucose Phase:
   Increase in blood glucose triggers beta cell release of insulin. Decrease in blood glucose triggers a cell release of glucagon.

Question 25

Why is there a larger GIP/GLP-1 response from oral vs. IV glucose?

Answer 25

due to oral and intestinal phases of insulin secretion (parasympathetic and incretin signals)

Question 26

What hormones besides Glucagon work to prevent Hypoglycemia?

Answer 26

catecholamines, cortisol, growth hormone

Question 27

What are the important GLUT transporters? Fxns?

Answer 27

***GLUT 1 = is in most cells and responsible for low level basal uptake of glucose

***GLUT 2 = is the glucose sensor for beta pancreatic cells
Thus initiates secretion of insulin secretion. Also present in hepatocytes, and found on basolateral epithelia of kidneys and intestine.

GLUT 3 = neurons, WBCs, sperm, placenta, preimplantation embryo

***GLUT 4 = controlled by insulin in resting skeletal muscle, cardiac muscle and adipocytes

GLUT 5 = transports fructose across apical membrane of intestine (also present in sperm).

GLUT 7 = transports glucose in endoplasmic reticulum

Question 28

How does Insulin signaling change target cell metabolism?

Answer 28

1. Insulin binds to tyrosine kinase receptor.
2. Receptor dimerizes.
3. Receptor phosphorylates insulin-receptor substrates (IRS)
4. Second messenger pathways alter protein synthesis and existing proteins.
5. Membrane transport is modified.
6. Cell metabolism is changed: Enzymatic shifts include promoting glucose storage as glycogen or triglycerides.

Question 29

How does Insulin induce GLUT4 movement to the cell membrane of muscle and adipose cells?

Answer 29

In the absence of insulin, glucose cannot enter the cell (no GLUT 4).

Insulin binding to target cells initiates a signal transduction cascade that causes synthesis/exocytosis of GLUT 4 receptors from the nucleus =>

GLUT 4 incorporates into the plasma membrane => allowing glucose to enter the cell!

Question 30

How is Insulin release from beta cells initiated?

Answer 30

Phospholipase C stimulates the release of intracellular Ca++ stores

Adenylate Cyclase stimulates the release of intracellular Ca++ stores

Closure of ATP-sensitive K+ channels which opens voltage dependent Ca++ channels => INSULIN RELEASE!