The Endocrine Pancreas

Question 1

Energy Intake controlled by which 2 hypothalamic centres?

Answer 1

○ FEEDING CENTRES = PROMOTES FEELING OF HUNGER + DRIVE TO EAT

	○ SATIETY CENTRE = PROMOTES FEELING OF FULLNESS BY SUPPRESSING FEEDING CENTRE

Question 2

Feeding & Satiety Centres controlled by what?

Answer 2

CONTROLLED BY COMPLEX BALANCE OF NEURAL & CHEMICAL SIGNALS + NUTRIENT PRESENCE IN PLASMA

	○ GLUCOSTATIC THEORY = FOOD INTAKE DETERMINED by BLOOD GLUCOSE - BG INCREASES causes EATING DRIVE TO DECREASE

	○ LIPOSTATIC THEORY = FOOD INTAKE DETERMINED by FAT STORES- FAT STORE INCREASES causes EATING DRIVE TO DECREASE

Question 3

What does energy output consist of?

Answer 3

Consist of ALL THE PROCESSES WE PERFORM TO STAY ALIVE + THOSE PERFORMED VOLUNTARILY + HEAT LOSS ASS. W/ THESE ACTIONS

Question 4

3 Categories of Energy Output

Answer 4

○ CELLULAR WORK = transporting molecules across membranes, growth & repair, storage of energy

	○ MECHANICAL WORK = movement (large scale/intracellularly)

	○ HEAT LOSS = ass. w/ cellular & mechanical work

• ONLY PART OF ENERGY OUTPUT VOLUNTARILY REGULATED = MECHANICAL WORK BY SKELATAL MUSCLES

Question 5

Metabolism Definition + Main 2 Types of Reactions + When do these types of reactions occur (in terms of eating/after eating)

Answer 5

INTEGRATION OF ALL BIOCHEMICAL REACTIONS IN THE BODY

ANABOLIC PATHWAYS = BUILD UP
CATABOLIC PATHWAYS = BREAK DOWN

AFTER EATING = Enter ABSORPTIVE STATE

• ANABOLIC PHASE: ingested nutrients supply energy needs of body + excess stored

BWTN MEALS & OVERNIGHT = Enter POST-ABSORPTIVE STATE/FASTED STATE

• CATABOLIC PHASE: pool of nutrients in plasma decreases, so rely on body stores to provide energy

Question 6

Why is maintaining [BG] important?

Answer 6

• MOST CELLS = can use FATS, CHOs, PROTEINS FOR ENERGY
  
  • BRAIN = OBLIGATORY GLUCOSE UTILISER, can only use GLUCOSE (KETONES in EXTREME STARVATION)○ Must maintain [BLOOD GLUCOSE] in POST-ABSORPTIVE STATE enough to meet brain’s req.○ If not = HYPOGLYCAEMIA OCCURS = COMA & DEATH○ Soooo… BG maintained via GLUCOSE SYNTHESIS from: GLYCOGENOLYSIS/GLUCONEOGENESIS (from glycogen or amino acids)

Question 7

Normal Range of Blood Glucose Concentration?

Answer 7

4.2-6.3mM

5 m moles usually normal

Hypoglycaemia < 3 mM [BG]

Question 8

Types of Pancreatic Islet Cells

Answer 8

• alpha cells produce GLUCAGON
  
  • beta cells produce INSULIN
  • delta cells produce SOMATOSTATIN
  • F cells produce pancreatic polypeptide (function not really known, may help control of nutrient absorption from GIT.)

Question 9

What is insulin + how is it produced?

Answer 9

• PEPTIDE HORMONE PRODUCED BY PANCREATIC β CELLS = STIMULATES GLUCOSE UPTAKE BY CELLS
  
  • PRODUCTION IS SAME AS GENERAL PEPTIDE HORMONE PRODUCTION + STORED IN PANCREATIC BETA CELL UNTIL CELL IN ACTIVATED

Question 10

Stimuli Increasing Insulin Secretion

Answer 10

1. Increased [BG]*****
2. Increased [amino acids]plasma
3. Glucagon (insulin required to take up glucose created via gluconeogenesis stimulated by glucagon)
4. Other (incretin) hormones controlling GI secretion and motility e.g. gastrin, secretin, CCK, GLP-1, GIP. (Released by ileum and jejunem in response to nutrients. Early insulin release prevents glucose surge when absorption occurs.)
5. Vagal nerve activity

Question 11

Primary Action of Insulin in Insulin Sensitive Tissues + What happens after insulin action complete?

Answer 11

• BINDS TO TYROSINE-KINASE RECEPTORS of INSULIN-SENSITIVE TISSUES (MUSCLE & ADIPOSE TISSUE)
  
  • STIMULATES TRANSPORT OF SPECIFIC GLUCOSE TRANSPORTERS TO MEMBRANE = GLUT-4 located in cytoplasm of unstimulated muscle & adipose cells
  • WHEN INSULIN STIMULATION STOPS = GLUT-4 TRANSPORTERS RETURN TO CYTOPLASMIC POOL

Insulin primarily degraded in liver + kidneys

Once insulin action complete = insulin-bound receptors internalised by endocytosis + destroyed by insulin protease - some recycled

Question 12

Primary Action of Insulin in Insulin Sensitive Tissues + What happens after insulin action complete?

Answer 12

• BINDS TO TYROSINE-KINASE RECEPTORS of INSULIN-SENSITIVE TISSUES (MUSCLE & ADIPOSE TISSUE)
  
  • STIMULATES TRANSPORT OF SPECIFIC GLUCOSE TRANSPORTERS TO MEMBRANE = GLUT-4 located in cytoplasm of unstimulated muscle & adipose cells○ INSULIN DOMINANT IN ABSORPTIVE STATE = ONLY HORMONE DECREASING [BG]
  • WHEN INSULIN STIMULATION STOPS = GLUT-4 TRANSPORTERS RETURN TO CYTOPLASMIC POOL

Insulin primarily degraded in liver + kidneys

Once insulin action complete = insulin-bound receptors internalised by endocytosis + destroyed by insulin protease - some recycled

Question 13

Additional Actions of Insulin (apart from glucose uptake)

Answer 13

Increases glycogen synthesis in muscle and liver

Stimulates glycogen synthase and inhibits glycogen phosphorylase

Increases amino acid uptake into muscle, promoting protein synthesis

Increases protein synthesis and inhibits proteolysis

Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis and inhibits lipolysis

Inhibits the enzymes of gluconeogenesis in the liver

Has a permissive effect on Growth Hormone

Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase (hypo/hyperkalaemia)

Question 14

Stimuli Decreasing Insulin Secretion

Answer 14

1. Low [BG]
2. Somatostatin (GHIH)
3. Sympathetic alpha2 effects
4. Stress e.g. hypoxia

Question 15

Why does Vagus activity cause increased insulin secretion?

Answer 15

VAGUS ACTIVITY STIMULATES RELEASE OF MAJOR GI HORMONES + STIMULATES INSULIN RELEASE

Sooo…. INSULIN RESPONSE TO IV GLUCOSE LOAD < RESPONSE TO EQUIVALENT ORAL GLUCOSE ADMINISTRATION

Question 16

What is Glucagon?

Answer 16

PEPTIDE HORMONE PRODUCED BY PANCREATIC α CELLS

Question 17

Primary Action of Glucagon

Answer 17

• RAISES BLOOD GLUCOSE
  
  • GLUCOSE MOBILISING HORMONE + ACTS MAINLY ON LIVER
  • PLASMA 1/2-LIFE = 5-10MINS + DEGRADED MAINLY BY LIVER

Question 18

Primary Action of Glucagon

Answer 18

• RAISES BLOOD GLUCOSE
  
  • GLUCOSE MOBILISING HORMONE + ACTS MAINLY ON LIVER
  • PLASMA 1/2-LIFE = 5-10MINS + DEGRADED MAINLY BY LIVER
  • PRIMARILY OPPOSES INSULIN + FORMS PART OF GLUCOSE COUNTER-REGULATORY CONTROL SYSTEM (incl. EPINEPHRINE, CORTISOL & GH)
  • MOST ACTIVE IN POST-ABSORPTIVE STATE

Question 19

Mechanism of Action of Glucagon

Answer 19

GLUCAGON RECEPTORS = GCPR COUPLED TO ADENYLATE CYCLASE/cAMP system = activates SPECIFIC LIVER ENZYMES (VIA PHOSPRYLATION)

RESULTS IN:

* INCREASED GLYCOGENOLYSIS
* ICREASES GLUCONEOGENESIS
* FORMATION OF KETONES FROM FA

Question 20

Stimuli Increasing Glucagon Secretion

Answer 20

Low [BG]

High [amino acids].Prevents hypoglycaemia following insulin release in response to aa.

Sympathetic innervation and epinephrine, beta 2 effects

Cortisol

Stress e.g. exercise, infection

Question 21

Stimuli Inhibiting Glucagon Secretion

Answer 21

Glucose

Free fatty acids (FFA) and ketones

Insulin (fails in diabetes so glucagon levels rise despite high [BG] )

Somatostatin

Question 22

Why is both glucagon & insulin secretion present in high amino acid meals?

Answer 22

• AMINO ACID MEALS CAUSE ACTIVATION OF INSULIN, EVEN THOUGH THERE IS NO GLUCOSE
  
  • INSULIN CAUSES A REDUCTION OF BLOOD GLUCOSE (BUT BG HAS NOT INCREASED)
  • THIS CAUSES HYPOGLYCAEMIA

Question 23

ANS Effects on Islet Cells

Answer 23

• INCREASED PARASYMP. ACTIVITY = INCREASES INSULIN & TO LESSER EXTENT GLUCAGON, in ass. w/ acticipatory phase of digestion
  
  • INCREASED SYMP. ACTIVITY = PROMOTES GLUCOSE MOBILISATION = INCREASED GLUCAGON, EPINEPHRINE & INHIBITS INSULIN - ALL FOR FIGHT/FIGHT RESPONSE

Question 24

What is somatostatin & what is its primary action?

Answer 24

PEPTIDE HORMONE RELEASED BY PANCREATIC DELTA CELLS & HYPOTHALAMUS

INHIBIT GIT ACTIVITY

• SLOWS DOWN ABSORPTION OG NUTRIENTS TO PREVENT EXAGGERATED PEAKS IN PLASMA CONCS.

NOT COUNTER-REGULATORY HORMONE IN CONTROL OF BLOOD GLUCOSE = IT STRONGLY SUPPRESSES INSULIN & GLUCAGON RELEASE