6 Pancreas

Question 1

What are the endocrine parts of the pancreas called?

Answer 1

Islets of langerhans - islands of endocrine cells (roughly 1 mil) in a sea of exocrine (digestive enzyme excreting) tissue

Question 2

What are the 5 types of endocrine cells in the islets of langerhans?

Answer 2

ß cells (60%) —> INSULIN
Alpha cells (25%) —> GLUCAGON
Delta cells (10%)
Gamma cells (4%)
Epsilon cells (1%)

Question 3

What are the dominant hormonal regulators produced by the pancreas

Answer 3

Insulin (produced by ß cells) and Glucagon (produced by a cells)

Shift the body between anabolism and catabolism/glucose sparing

Generally oppose each other

Question 4

What do delta cells of the islets of langerhans secrete?

Answer 4

Somatostatin (inhibits digestive function, GHIH)

Question 5

What do gamma cells of the islets of langerhans secrete?

Answer 5

Pancreatic polypeptide (putatively reduces appetite and food intake)

Question 6

What do epsilon cells of the islets of langerhans secrete?

Answer 6

Ghrelin (appetite stimulating hormone)

When you’re grilling, the smell makes you release Ghrelin

Question 7

Besides Insulin, what else do beta cells release?

Answer 7

Amylin - acts on the CNS to suppress appetite

Question 8

What does proinsulin look like?

Answer 8

Alpha and beta peptide chains connected by a C-peptide.

The alpha and beta chains are linked by 2 disulfide bonds.

The c-protein is cleaved from the proinsulin to form insulin

Question 9

C-peptide is a marker of…

Answer 9

Insulin production and ß-cell function.

Used therapeutically to determine ß-cell function (because exogenous insulin doesn’t have c-peptide)

Question 10

How does glucose stimulate insulin release?

Answer 10

Excitation-secretion coupling in ß-cells

Glucose enters via GLUT2 (facilitated diffusion)
Glucose+PO43 —> glucose-6-phosphate (trapped)
ATP closes K+ channel
Decreased K+ flux depolarizes cell membrane
Voltage-gated Ca2+ channels open
Ca2+ enters ß-cell and triggers exocytosis of insulin vesicles
Insulin secreted into circulation

Question 11

Effect of insulin on carbohydrate stores

Answer 11

Decreased blood glucose and storage
Increased glucose uptake by skeletal muscle and adipose tissue
Glycogenesis (skeletal muscle and liver)
Glycogenolysis (liver)
Gluconeogenesis (liver)

Question 12

Effect of insulin on lipid stores

Answer 12

Decreased blood fatty acids and increased storage
Increased glucose uptake into adipocytes
Increased enzymes that produce fatty acids (increased lipogenesis)
Increased fatty acid uptake
Decreased lipolysis

Question 13

Effect of insulin on protein stores

Answer 13

Decreased blood amino acids and increased storage
Increased amino acid uptake
Increased protein-synthesizing machinery
Decreased protein degradation

Question 14

Insulin recruits ______ to cell surface

Answer 14

GLUT4: insulin dependent transporter in most other cells of the body

Other non-insulin dependent GLUT transporters:
GLUT1: BBB
GLUT3: neurons

GLUT2 is also insulin dependent GLUT4 is the main one to think of

Question 15

What is the consequence of low levels of insulin secretion on glucose uptake?

Answer 15

Glucose transporters can’t get to surface of the cell and therefore can’t take up glucose

Question 16

Insulin stimulates __________ pathways to regulate numerous possible intracellular pathways

Answer 16

MAP kinase

Can lead to general gene expression, cell growth, differentiation and other processes

Disruption of intracellular signaling is key to understanding insulin resistance and Type II DM

Question 17

Most common endocrine disorder?

Answer 17

Diabetes Mellitus - results form high blood sugar levels over a prolonged period

Question 18

Type I DM is also known as…

Answer 18

Insulin dependent DM - due to lack of insulin secretion

Autoimmune: T-lymphocytes destroy ß-cells

Can also be idiopathic or environmental

Question 19

Type II DM is also known as

Answer 19

Non-insulin dependent DM - due to tissue resistance to insulin

Can be mild to severe

Often the result of life-style choice

Acute: characteristic of post-absorptive state

Chronic: includes a range of symptoms culminating in death

Question 20

Diagnosis of DM is through measurement of …

Answer 20

Glycated hemoglobin, HbA1c

Value of >6.5% HbA1c reflects above average blood glucose over the previous 3 months

Question 21

By what mechanism does DM cause polyphagia and polydipsia?

Answer 21

Hyperglycemia results from inadequate uptake of glucose into cells and an increased output of glucose from liver

Elevated glucose in the glomerular filtrate is greater than what the tubular cells can reabsorb

The osmotic effect of glucosauria draws additional water into the filtrate

Excess fluid lost from the body results in dehydration

Polyphagia occurs as a consequence of increase in appetite (cells are starving b/c glucose not getting in - GLUT4 not active)

Polydipsia occurs in an attempt to compensate for effects of dehydration

Question 22

The chronic dehydration resulting from DM eventually leads to what?

Answer 22

Dehydration state results in decreased blood volume

Peripheral circulatory failure can affect several vita organs

Renal failure may occur when GFR declines due to inadequate filtration pressure

Brain function declines resulting in failure to oxygenate the brain —> DEATH

Cells in the body shrink due to an osmotic shift of water into ECR and blood

Nerve cells lose their ability to maintain correct membrane potentials and form action potentials

Question 23

In DM patients, large-scale mobilization of fatty acids from triglyceride stores leads to what?

Answer 23

Hepatic use of fatty acids —> kenos is

Ketone bodies in the blood disrupt blood pH resulting in METABOLIC ACIDOSIS

Respiratory ventilation may increase in an effort to vent CO2 and shift pH up

Severe acidosis may depress brain function —> COMA —> DEATH

Question 24

How is hyperglycemia aggravated in DM patients?

Answer 24

Lack of insulin results in a shift towards more protein catabolism

Muscles atrophy and weight loss occurs

In children, proper growth is compromised

Excess blood amino acids shift towards greater gluconeogenesis in teh liver, contributing to the existing hyperglycemia

Question 25

How does insulin excess occur?

Answer 25

Insulin overdose (insulin shock) - a sugary snack will recover normal blood glucose Reactive hypoglycemia - in an extreme response to glucose, beta cells release too much insulin; DON’T give sugary snack but control by limiting carbs in diet Use C-peptide levels to determine which it is if you don’t know Effects are dangerous - can lead to depressed brain function and LOC

Question 26

Glucagon is stimulated by ...

Answer 26

Low glucose Epinephrine*** Vagal stimulation***

Question 27

Glucagon is inhibited by...

Answer 27

High glucose Somatostatin***

Question 28

What IS glucagon?

Answer 28

14 amino acid polypeptide expressed in liver, intestine, brain and pancreas Produced as proglucagon and proteolytically process to yield glucagon and incretin (GLP1) GLP1 is released from intestine in response to high glucose levels in teh intestine GLP1 increases insulin release from ß-cells

Question 29

Glucagon mainly targets ________ to stimulate________.

Answer 29

Liver —> hepatic glucose output It INCREASES PLASMA GLUCOSE LEVELS Opposes the effects of insulin and GLP1 Increases gluconeogenesis and glycogenolysis In adipose tissue, has a pro-lipolysis effect

Question 30

Glucagon release is...

Answer 30

Increased by hypoglycemia**** Increased by epi, CCK, vagal stimulation, fasting, exercise Decreased by hyperglycemia, somatostatin, insulin, fatty acids, and keto acids Increased by dietary protein (ARGININE), in absence of carbs (if a meal is a combo of protein and carbs, no effect on glucagon, but A STEAK —> increased glucagon)

Question 31

Glucagon effects on carbohydrate stores

Answer 31

Increase blood glucose Increased gluconeogenesis and release Increased glycogenolysis Decreased glycogen synthesis

Question 32

Glucagon effects on lipid stores

Answer 32

Increased blood fatty acids and ketones Decreased triglyceride synthesis Increased lipolysis and release of fatty acids from adipose tissue Increased ketone production

Question 33

Glucagon effects on protein stores

Answer 33

``` Minimal effect on blood amino acids Decreased hepatic protein synthesis Increased hepatic protein degradation Increased gluconeogenesis No effect on skeletal muscle proteins, the major protein storage site ```

Question 34

What is somatostatin?

Answer 34

14 amino acid polypeptide hormone produced in the delta cells Release stimulated by high fat, carbs, and protein-rich meals Release in the pancreas not well understood, but inhibits the release of insulin and glucagon by hyperpolarizing the beta and alpha cells (paracrine effect) Has generalized inhibitory effects on the GI tract (smooths out the spikes in blood glucose that can occur with meals) Well-known brain peptide released in the median eminence of the hypothalamus to inhibit the release of GH by anterior pituitary

Question 35

How else is glucose regulated (besides insulin and glucagon)?

Answer 35

``` Diabetogenic hormones: Epinephrine Cortisol GH and IGF-1 (Thyroid Hormone) - not very responsive, onset too slow ``` The brain: hypothalamic control of fuel management • Autonomic control of hormone release • Senses nutrients and hormones associated with nutrient levels

Question 36

Epinephrine effects on blood glucose

Answer 36

Increased glycogenolysis, gluconeogenesis and glucagon secretion Decreased insulin secretion via alpha-adrenergic stimulation of beta cells

Question 37

Cortisol effects on blood glucose

Answer 37

Increase gluconeogenesis and glucose sparing (use fatty acids instead) Decreased glucose uptake in tissues other than the brain In liver, promotes glycogenolysis in early-stage fasting and glycogen synthesis in late-stage fasting

Question 38

GH effects

Answer 38

On blood glucose - decreased glucose uptake by muscles and increased glucose sparing On fatty acids - increased lypolysis On amino acids - increased uptake into cells, decreased blood amino acids On muscle protein - Increased protein synthesis, decreased protein degradation, increased DNA/RNA synthesis Released during deep sleep, stress, exercise, hypoglycemia Promotes growth, SMALL ROLE in fuel metabolism

Question 39

What are the main areas of the brain involved in neural control of glucose?

Answer 39

CNS has receptors for nutrient levels, esp glucose detection in ARCUATE NUCLEUS, and hormones The hypothalamus directly and indirectly regulates glucose homeostasis by: • Insulin and glucagon secretion (via ANS0 • Hepatic glucose output • Glucose uptake by skeletal muscles Pathways that regulate glucose balance integrate with brain circuits that control energy balance and control body weight

Question 40

What is a positive energy balance?

Answer 40

Food intake exceeds energy expended Remaining stored as adipose tissue

Question 41

What is a negative energy balance?

Answer 41

Food intake does not meet energy needs Body supplies remainder

Question 42

__________ are primarily responsible for regulating food intakes and body composition

Answer 42

Hypothalamic brain centers