Endocrine Pancreas

Question 1

Endocrine cells of the pancreas secrete what?

What role does it play?

Cells arranged in clusters called ____.

What innervated it?

Answer 1

Insulin, glucagon, somatostatin

Regulating lipid, CHO, and AA metabolism

Islets of Langerhans

Adrenergic, cholinergic, peptidergic neurons

Question 2

Cells of the endocrine pancreas and their secretions

Answer 2

Beta cells (central): insulin and C peptide

Alpha cells (peripheral): glucagon

Gamma cells (between alpha and beta cells): somatostatin; send dendrite-like processes to beta cells

Question 3

How do the cells of the Islets of Langerhans communicate with each other?

Answer 3

Gap junctions

Blood supply: islets receive 10% of pancreatic blood flow; venous blood from beta cells carries insulin to alpha and gamma cells (center to periphery)

Paracrine actions work in reverse of blood flow

Question 4

Insulin is a major ____ hormone.

Secreted in response to _____ ingestion.

____ is its major stimulator factor

Answer 4

Anabolic

CHO and/or protein

Glucose

Question 5

Signal peptide with A and B chains connecting peptide (C peptide); no disulfide bonds

Answer 5

Preproinsulin

Question 6

No signal peptide; C peptide still attached to insulin; packaged into secretory granules; proteases cleave proinsulin***

Answer 6

Proinsulin

Question 7

____ is the marker of endogenous insulin secretion ***

Answer 7

C peptide

Question 8

Describe the step to insulin release

Answer 8

Glucose enter cell by GLUT-2 (always on membrane); GLUT-4 (inside cell, on membrane when needed)

Glucose is phosphorylated by glucokinase

Glucose-6-phosphate is oxidized promoting ATP generation

ATP closes the INWARD RECTIFYING K channel (increase membrane potential, becoming more positive)

Plasma membrane is depolarized

Activation of VOLTAGE-GATED Ca channels; Ca enters

Initiates mobilization of insulin containing vesicles to plasma membrane and exocytosis

Question 9

Rise in ATP ____ K channels

____ receptor is associated with ATP-dependent K channels; increase insulin secretion (membrane depolarization, Ca enter, treatment of type 2 DM)

____ secretion measures function of beta cells and endogenous insulin secretion

Answer 9

Closes

Sulfonylurea

C peptide

Question 10

Insulin release is ____.

First phase insulin secretion is ____ first in diabetic pt

Secondary responses ____. ***

Answer 10

Biphasic

Lost

Increase

Question 11

GI peptides, CCK, gastrin, glucagon, phospholipase C, ACh (parasympathetics) ____ insulin secretion.

Somatostatin ____ insulin secretion.

Act independent of ____.

Answer 11

Stimulate

Inhibit

Glucose

Question 12

Insulin binds to a ____ receptor

This receptor autophosphorylates itself and ____.

Insulin-receptor complex is ____ by target cell.

Down Regulation of receptor by ____.

Answer 12

Insulin

Other proteins

Internalized

Insulin

Question 13

Glucose enters cell through GLUT4

Answer 13

???? **

Question 14

Activation of AMP-kinase (AMPK) results in GLUT4 translocation to plasma membrane allowing ____ uptake…acts ____ of insulin.

Stimulated by ____.

Answer 14

Glucose

Independent

Muscle contractions

Question 15

Insulin actions on skeletal muscle

Answer 15

Increase glucose uptake (GLUT4)

Increase glycogen synthesis (hexokinase, glucokinase, glycogen synthase)

Increase glycolysis and CHO oxidation (hexokinase, PFK, PDH)

Increased protein synthesis

Decrease protein breakdown

Question 16

Insulin actions on liver (“put on the break”)

Answer 16

Promotes glycogen synthesis (glucokinase, glycogen synthase)

Increases glycolysis and CHO oxidation (glucokinase, PFK, pyruvate kinase)

Decreases gluconeogenesis (PEPCK, fructose-1,6-bisphosphatase, G6P phosphatase)

Increase hexose monophosphate shunt

Increases pyruvate oxidation

Increase lipid storage and decreases lipid oxidation (increase malonyl CoA)

Increases protein synthesis, decrease protein breakdown

Question 17

Insulin actions on adipose tissue

Answer 17

Increase glucose uptake (GLUT4)

Increased glycolysis

Decreased lipolysis (inhibits HSL)

Promotes uptake of fatty acids (LPL)

Question 18

Factors that stimulate insulin secretion

Answer 18

Increased blood glucose
Increased blood AA
Increased blood FA and keto acids
Glucagon
Cortisol
Glucose-dependent insulinotropic peptide (GIP)
Vagal stimulation (through ACh)
Potassium
Sulfonylurea drugs
Obesity

Question 19

Factors that inhibit insulin secretion

Answer 19

Decreased blood glucose
Fasting
Exercise
Somatostatin
Alpha-adrenergic agonists
Diazoxide (K channel activator)

Question 20

Coordinated actions of insulin (8)

Answer 20

Increased glucose uptake into cells (decrease blood glucose)
Increased glycogen formation
Decreased glycogenolysis
Decreased gluconeogenesis
Increased protein synthesis (decrease blood AA)
Increased fat deposition (decrease blood FA)
Decrease lipolysis (decrease blood keto acids)
Increased K uptake into cells (decreased blood K)

Question 21

BMI

Answer 21

Body mass index

Weight (kg)/height (m2)

18.5-24.9 normal
25.0-29.9 overweight
30-39.9 obese
>40

Question 22

This is a fasting blood profile of a pt with type 1 DM

This is a fasting blood profile of a pt with type 2 DM

Answer 22

Increase glucose
Decrease insulin
Decrease C peptide
Increase HbA1c

Increase glucose
Increase insulin
Increase C peptide
Increase HbA1c

Question 23

Type 1 DM:

____ insulin secretion.

Destruction of ____ cells.

___ blood glucose, FA, ketoacids, AA

Decreased utilization of ketoacids result in ____.

Answer 23

Inadequate

Beta

Increased

Diabetic ketoacidosis (DKA)

Hyperkalemia, osmotic diuresis, glucosuria

Question 24

Hyperkalemia is a shift of ____ out of cells.

Answer 24

K *****

Question 25

Treatment of type 1 DM has drawbacks

Answer 25

Painful Lag between glucose measurement and insulin dosing Delayed absorption of insulin following injections Poor blood glucose control leads to hyperglycemia

Question 26

Treatment for type 1 DM

Answer 26

Beta cell mimetic designer cells (HEK-beta) show glucose-induced insulin release performance comparable to beta cell lines and human islets

Question 27

Type 2 DM: Insulin resistance Progressive exhaustion of active ____ cells due to ____ factors.

Answer 27

Beta Environmental

Question 28

Progression of insulin resistance in type 2 DM: Reactive hyperinsulinemia followed by _____. Obesity induced insulin resistance includes what?

Answer 28

Hypoinsulinemia Decreased GLUT4 uptake of glucose in response to insulin Decreased ability of insulin to repress hepatic glucose production Inability of insulin to repress adipose tissue uptake

Question 29

Insulin resistance of type 2 DM: Post-receptor signaling results in ____ glucose transporter number and mobilization

Answer 29

Decreased

Question 30

Treatment of type 2 DM ****

Answer 30

Caloric restrictions, exercise Sulfonylurea drugs Incretin analog of GLP-1 Slow absorption of CHO Metformin

Question 31

When you eat a meal a with glucose (oral glucose) you will get ____ insulin response

Answer 31

Higher

Question 32

Incretin used to treat ____. Stimulates ____ secretion. Inhibits ____ secretion.

Answer 32

Type 2 DM Insulin Glucagon

Question 33

Glucagon is stored in granules of ____ cells. Stimulated by a ____ in blood glucose. Stimulated by ____ in AA, fasting, CCK, beta-adrenergic agonists, ACh What inhibits glucagon?

Answer 33

Alpha Decrease Increase Insulin, somatostatin, FA, ketoacids

Question 34

Actions of glucagon on liver Other actions

Answer 34

Increases blood glucose Increases gluconeogenesis Increases glucogenolysis Inhibits glycogen synthesis Lipolysis of adipose tissue and skeletal m (increases FA) Ketoacids produced form FA