17. Endocrine Pancreas

Question 1

The endocrine cells of the pancreas secrete 3 separate hormones

Beta cells secrete ____

Alpha cells secrete ____

Delta cells secrete ______

Answer 1

Insulin (and C peptide)

Glucagon

Somatostatin

Question 2

The beta, alpha, and delta cells of the pancreas are organized into clusters called ____

Answer 2

Islets (of langerhans)

Question 3

Which cells of the pancreas are neuronal in appearance and send dendrite like processes to beta cells?

Answer 3

Delta cells

Question 4

Most ____ cells of the pancreas are centrally located, while most _____ are peripherally located

Answer 4

Beta; alpha

Question 5

How do individual islets in the endocrine pancreas communicate with each other?

Answer 5

Via gap junctions - rapid cell-cell communication

Question 6

Describe blood supply to the endocrine pancreas - which cells receive blood first?

Answer 6

Venous blood first flows to center for insulin; venous blood from beta cells carries insulin to alpha and delta cells

[flows through periphery, insulin rich blood inhibits glucagon release from alpha cells]

Question 7

What is the major stimulating factor for insulin secretion?

Answer 7

Glucose

Question 8

Insulin is a _____ hormone made up of 2 chains linked by _____ bridges

Answer 8

Peptide; disulfide

Question 9

_______ = signal peptide with A and B chains with connecting C peptide - NO disulfide bonds

Answer 9

Preproinsulin

[preproinsulin —> proinsulin —> Insulin + C peptide]

Question 10

______= no signal peptide because C peptide still attached to insulin; packaged into secretory granules, proteases can cleave it

Answer 10

Proinsulin

Question 11

Once synthesized, insulin and cleaved C peptide are packaged together in ______

Answer 11

Secretory vesicles

Question 12

What compound can be used as a marker of endogenous insulin secretion?

Answer 12

C peptide

Question 13

Steps for insulin release:

1. Glucose enters cell via ______
2. Glucose is phosphorylated by a ________
3. G6P is oxidized, promoting ___ generation
4. ATP closes the inward rectifying ____ channel
5. Plasma membrane is depolarized
6. Activation of voltage gated ___ channels leading to its entry into the cell
7. Mobilization of insulin is initiated

Answer 13

GLUT2
Glucokinase
ATP
K
Ca

Question 14

Rises in ATP have what effect on K channels in beta cells?

Answer 14

Rises in ATP close the K channels

Question 15

The sulfonurea receptor associated with ATP-dependent K channels increase insulin secretion. what effect does this have on membrane depolarization?

Answer 15

Causes membrane depolarization to occur more easily d/t increased Ca entry - so this can be targeted and used for tx of T2DM

Question 16

C peptide secretion is used as a tool to measure function of beta cells and endogenous insulin secretion. C peptide is typically secreted in the ____

Answer 16

Urine

Question 17

Describe the biphasic release of insulin and how this is affected in diabetics

Answer 17

When plasma glucose increases:

Phase 1 = initial spike in insulin secretion

Phase 2 = gradual sustained rise in insulin secretion

In diabetes — phase 1 is the first phase lost

Question 18

Besides blood glucose levels, what are some other modulators of insulin secretion?

Answer 18

Activating:
GI peptides
Glucagon
ACh

Inhibitory:
Somatostatin

Question 19

Once insulin binds its receptor, it ________ itself and other proteins. The entire complex is internalized by target cell, leading to anabolic growth effects and metabolic effects, eventually leading to activation of ______ and ______ which have a negative feedback effect on the receptor itself

Answer 19

Autophosphorylates; mTORC1; SREBP1c

Question 20

Glucose uptake occurs through _______, once vescicles containing this transporter to the membrane

Answer 20

GLUT4

Question 21

Activation of _______ results in GLUT4 transloaction to the plasma membrane INDEPENDENT of insulin

Answer 21

AMP-kinase

[active in times of low energy]

Question 22

Actions of insulin on skeletal muscle

Answer 22

Increased glucose uptake via GLUT4

Increased glycogen synthesis via activity of hexokinase and glycogen synthase

Increased glycolysis and CHO oxidation via activity of hexokinase, PFK, PDH

Increased protein synthesis

Decreased protein breakdown

Question 23

Action of insulin on liver

Answer 23

Promotes glycogen synthesis via glucokinase and glycogen synthase

Increases glycolysis and CHO oxidation via glucokinase, PFK, PK

Decreases gluconeogenesis

increases hexose monophosphate shunt (protein anabolism)

Increases pyruvate oxidation

Increases lipid sotrage and decreases lipid oxidation

Increases protein synthesis and decreases protein breakdown

Question 24

Insulin actions on adipose tissue

Answer 24

Increased glucose uptake via GLUT4

Increased glycolysis

Decreased lipolysis

Promotes uptake of fatty acids

Question 25

What effect does insulin have on K+ uptake into cells?

Answer 25

Increases K uptake into cells (thus decreasing blood levels of K)

Question 26

Which of the following increases insulin secretion? ``` A. Fasting B. Somatostatin C. Cortisol D. Exercise E. Diazoxide ```

Answer 26

C. Cortisol

Question 27

Type 1 diabetes is often d/t autoimmune destruction of ___ cells, leading to inadequate insulin secretion Results in increased BG, fatty acids, _______, amino acids Decreased utilization of ketoacids results in ______

Answer 27

Beta Ketoacids DKA (diabetic ketoacidosis)

Question 28

What effect does T1DM have on blood potassium levels?

Answer 28

Increases shift of K+ out of cells —> hyperkalemia [intracellular concentration of K is low, lack of insulin effect on Na/K ATPase, total K levels usually low d/t polyuria and dehydration]

Question 29

What effect does T1DM have on diuresis?

Answer 29

Causes osmotic diuresis and glucosuria [also polydipsia d/t increased polyuria]

Question 30

Which type makes up 95% of DM cases?

Answer 30

T2DM

Question 31

T1DM is insulin deficiency. What causes T2DM?

Answer 31

Insulin resistance — progressive exhaustion of beta cells d/t environmental and genetic factors

Question 32

The progression of insulin resistance in t2DM begins as reactive ______ followed by relative _____

Answer 32

Hyperinsulinemia; hypoinsulinemia

Question 33

Obesity induced insulin resistance begins with decreased ____ uptake of glucose in response to insulin (classical skeletal muscle impairment) Decreased ability of insulin to repress _____ glucose production (may be earliest response) Inability of insulin to repress _____ tissue uptake via LPL and lipolysis via HSL

Answer 33

GLUT4 Hepatic Adipose

Question 34

T/F: those with T2DM are more prone to ketoacidosis than T1DM patients

Answer 34

False; other way around

Question 35

Treatment options for T2DM

Answer 35

Caloric restriction, weight reduction, PE Insulin secretagogues - sulfonurea drugs, incretin analogues Insulin sensitizers Bariatric surgery Alpha-glucosidase inhibitors, amylin analogues

Question 36

What is the incretin effect that insulin has on skeletal muscle?

Answer 36

Oral intake elicits better response than injection

Question 37

What are some incretin hormones? What effects do they have on insulin secretion, glucagon secretion, and gastric emptying?

Answer 37

Intestine derived hormones = GLP-1, GIP Stimulate insulin secretion, inhibit glugcagon secretion, slow gastric emptying

Question 38

Will type 2 diabetics show a normal, enhanced, or reduced incretin effect?

Answer 38

Reduced

Question 39

______ is a hormone in the same peptide family as secretin and GIP, stored in dense granules of alpha cells

Answer 39

Glucagon

Question 40

What is the primary major stimulus for secretion of glucagon?

Answer 40

Major stimulus = Decreased blood glucose via GLUT, K(ATP), and VDCC in alpha cell membrane (similar to beta cells) [may also be stimulated by increased aa like arginine and alanine, fasting, CCK, beta adrenergic agonists, ACh]

Question 41

What effect does insulin have on glucagon production and secretion?

Answer 41

Inhibits

Question 42

Which of the following stimulates glucagon secretion? ``` A. Insulin B. Somatostatin C. Fatty acids D. Ketoacids E. None of the above ```

Answer 42

E. None of the above

Question 43

The major actions of glucagon are on what organ?

Answer 43

Liver

Question 44

What effect does glucagon have on the liver in terms of glucose formation, gluconeogenesis, glycogenolysis, and glycogen synthesis?

Answer 44

Increases glucose formation via gluconeogenesis and glycogenolysis Inhibits glycogen synthesis

Question 45

What effect does glucagon have on lipolysis in adipose and skeletal muscle?

Answer 45

Stimulates lipolysis [which produces ketoacids from fatty acids]