Endocrine: Pancreas Physiology

Front 1

List the metabolic actions of insulin in liver

Back 1

- Decreases gluconeogenesis
- Increases glycogenesis
- Increases lipogenesis

Front 2

List the metabolic actions of insulin in striated mm

Back 2

- Increases glucose uptake
- Increases glycogenesis
- Increases protein synthesis

Front 3

List the metabolic actions of insulin in adipose tissue

Back 3

- Increases glucose uptake
- Increases lipogenesis
- Decreases lipolysis

Front 4

What is the islet of Langerhans?

Back 4

Regions of pancreas that contain endocrine cells

Front 5

What is the structure of proinsulin?

Back 5

Insulin + C-peptide

Front 6

List the hormones secreted by endocrine cells in pancreas and their feedback fxn

Back 6

alpha = glucagon; autocrine activation
ß = insulin + amylin; autocrine activation & inhibits alpha cells
∂ = somatostatin; inhibits alpha & ß cells

Front 7

Describe insulin synthesis

Back 7

Occurs in ß cells nucleus & ER

Synthesize pre-proinsulin, which is cleaved in the ER to proinsulin, from which C-peptide is excised to form mature insulin.

Insulin + C-peptide packaged by Golgi into secretory granules

Front 8

Describe amylin secretion and its effects

Back 8

Co-secreted 1:100 with insulin

Inhibits alpha cells to suppress post-prandial glucagon & restrain gastric emptying

Front 9

Of what is C-peptide indicative?

Back 9

Since C-peptide is cosecreted with insulin, it is used to monitor insulin production & ß cell fxn

Front 10

What is the half-life of insulin?

Back 10

3-5 minutes

Front 11

Describe insulin secretion

Back 11

1) Glucose enters ß cells by GLUT2R
2) It's immediately phosphorylated by Glucokinase for entry into glycolysis
3) activates CAC cycle & electron transport pathway in mitochondrion, yielding ATP
4) ATP opens ATP-dependent K+ channel
5) K+ influx hyperpolarizes cell, opening Ca2+ channels
6) Ca2+ mediates exocytosis of secretory granules, which release insulin

Front 12

What is the role & mechanism of sulfonylurea in insulin secretion?

Back 12

--->Increases Insulin secretion <---

Binds sulfonylurea receptor that partners to the ATP-dependent K+channel

Binding of sulfonylurea causes K+ channel to depolarize (close), therefore increasing insulin secretion

Front 13

Describe the mechanism of insulin-induced glucose uptake?

Back 13

1) Insulin binds to its receptor tyrosine kinase, producing IRS binding proteins
2) IRS BPs induce Ras complex, which increases gene transcription
3) IRS BPs also induce other pathways that activate glucose transporter and deliver it to cell surface
4) Glucose transporter actively takes up glucose into the cell

Front 14

Which glucose transporter protein mediates basal glucose uptake in the brain vasculature? Where else it it expressed?

Back 14

GLUT-1

Expressed in all tissues

Front 15

Which glucose transporter protein acts as a "glucose sensor" in the beta cell and what is unique about it?

Back 15

GLUT-2

Has a lower affinity for glucose in order to prevent pancreas from becoming overstimulated from low levels of glucose

Front 16

Which glucose transporter protein is insulin-regulated & where is it expressed?

Back 16

GLUT-4

Expressed in skeletal mm & adipose tissue

Front 17

Which glucose transporter protein is expressed in neurons?

Back 17

GLUT-3

Front 18

Describe the glucose affinity of each glucose transporter protein

Back 18

GLUT-1: high
GLUT-2: lower
GLUT-3: high
GLUT-4: insulin-dependent

Front 19

Where is the GLUT-2 receptor expressed?

Back 19

Beta cell, liver, GI, kidney

Front 20

Describes insulin's effects on the liver

Back 20

Inhibits ketogenesis & gluconeogenesis

Stimulates glycogenesis & FA synthesis

Front 21

Describes insulin's effects on the muscle

Back 21

Stimulates glucose uptake via GLUT-4 & glycogenesis

Increases protein synthesis by stimulating uptake of neutral amino acids and increasing mRNA translation

Front 22

Where is excess glucose stored in the body and in what forms?

Back 22

Liver = glycogen, fatty acids
Muscle = glycogen
Adipocytes = triglyceride (fat); *produced from FFA or glucose

Front 23

What effects are stimulated by low levels of insulin?

Back 23

---> Catabolism <---

Liver: Increased glycogenolysis, then gluconeogenesis; decreased FA synthesis and glycogenesis; ketogenesis from FAs in severe low insulin

Mm: Decreased glycogenesis

Adipose: Lipolysis, decreased lipogenesis

Front 24

Describe insulin's effects on adipose tissue

Back 24

- Stimulates glucose uptake via GLUT-4
- Stimulates FFA uptake via activation of lipoprotein lipase for TG storage

Front 25

What is the rate-limiting step of glucose uptake in the liver?

Back 25

*Glucokinase* (glu -> glu-6-p)

Needed to keep the intracellular [glucose] low to favor entry of glucose into cell

Front 26

What is the effect of exercise on glucose?

Back 26

Increases glucose transport/uptake to the muscles via a different transporter at the cell surface

Front 27

Which tissues use ketone bodies & how do they produce energy?

Back 27

All tissues except liver

Incorporated into acetyl-CoA and used in the citric acid cycle

Front 28

Which tissues use fatty acids?

Back 28

All tissues except the brain

Front 29

What is a counter-regulatory hormone?

What are the counter-regulatory hormones to insulin?

Back 29

Hormone with the opposite effect of a specific hormone

Glucagon, Catecholamines (E, NE), Cortisol, GH

Front 30

What are the effects of glucagon?

Back 30

Counter-regulatory to insulin:

Liver: glycogenolysis (minutes); gluconeogenesis (hours); ketogenesis (extreme hypoglycemia)

Acts through T-protein coupled receptor to signal via cAMP & downstream kinases

Front 31

Where is glucagon produced and how is its production stimulated?

Back 31

Islet alpha cells

Stimulated by hypoglycemia and catecholamines; inhibited by high [glucose]

Front 32

In a hypoglycemic state, what energy sources are utilized and in what order?

Back 32

1) Glycogen
2) Lactate, glycerol, alanine (gluconeogenesis)
3) FFAs --> ketone bodies

Front 33

Describe the clearance of glucagon (include half-life).

Back 33

Half-life: 3-6 minutes
Removed by liver & kidneys

Front 34

How is glucagon regulated?

Back 34

- Inhibited by insulin

- Inhibited by Somatostatin-14

- Glucagon-like protein (GLP)-1 secreted from intestinal L cells post-meal; acts on pancreas to increase insulin & inhibit glucagon release

Front 35

What is the effect of GLP-1? Are they short or long-acting and why?

Back 35

- increases insulin
- inhibits glucagon release
- stimulates satiety in hypothalamus
- acts on stomach to inhibit gastric secretion & motility
- secreted with GLP-2


Short-acting because rapidly inactivated by dipeptidyl peptidase (DPP-IV) in circulation

Front 36

What is GLP-2?

Back 36

Glucose-like peptide cleaved from proglucagon and co-secreted with GLP-1

acts on intestine to increase absorption and decrease motility

Front 37

Where is somatostatin synthesized?

Back 37

Hypothalamus, pancreatic ∂-cells, GI tract

Front 38

Where does somatostatin act?

Back 38

SMS-14: pancreas
SMS-28 = gut

Front 39

Describe somatostatin's effects

Back 39

SMS-14 = more potent glucagon inhibitor

SMS-28 inhibits GH & insulin release; SMS-14 does too, but to a lesser extent

Front 40

What is the effect of catecholamines?

Back 40

- Catecholamines rise when [glucose] low

- Stimulates glycogenolysis
- Stimulates gluconeogenesis (liver)
- Stimulates lipolysis (activates hormone-sensitive lipase)

- When elevated, cause a change in mental status, shakiness, sweating
*Sx similar to hypoglycemia, but not true hypoglycemia

Front 41

What is the effect of cortisol?

Back 41

- Stimulates proteolysis
- Stimulates gluconeogenesis
- Induces insulin resistance
- Stress response
- Part of dawn phenomenon

Front 42

What is the dawn phenomenon? Which hormones are included?

Back 42

Peak of serum hormone levels at dawn (~5-6am)

Applies to Cortisol & Growth Hormone

*Note: Insulin is at its lowest at dawn

Front 43

What is the effect of GH?

Back 43

Stimulates lipolysis, protein synthesis, and insulin resistance

Part of dawn phenomenon and stress response

Front 44

Why are young patients with GH deficiency susceptible to hypoglycemia when in a fasting state?

Back 44

GH stimulates lipolysis in order to spare glucose from being burned as fuel.

∴ in fasting state, GH-deficient pts spare less glucose => hypoglycemia

Front 45

Explain how polydipsia, polyuria, and dehydration occur in insulin deficiency

Back 45

- Renal threshold for glucose (RTG) is 180-200mg/dl
- At RTG, tubules cannot reabsorb anymore glucose from blood
- More glucose in lumen increases osmotic pressure, leading to water retention in the lumen (decreased reabsorption)
- Water & glucose excreted in urine

Front 46

True or False: Glucose is normally secreted in urine

Explain.

Back 46

False. Normally reabsorbed in tubules, except when renal threshold for glucose is

Front 47

How is weight loss mediated in insulin deficiency?

Back 47

Insulin deficiency mediates an excess of counter-regulatory hormones which increase proteolysis & gluconeogenesis for glucose production

Catabolism reduces mm and adipose tissue (fat)

Leads to weight loss and hyperglycemia