EXAM3_L28_Insulin_Glucagon

Question 1

What is diabetes fasting glucose levels?

Answer 1

> 126mg/dL

7mmol/L

Question 2

1 hour postprandial Normal blood glucose

Answer 2

up to 145 mg/dL

8mmol/L

Question 3

Normal Fasting blood glucose?

Answer 3

70-110mg/dL

3.9-6.1mmol/L

Question 4

Symptomatic Hypoglycemia

Question 5

What are the responsibilities of the Pancreas?

What 3 cell types of the pancreas?

Answer 5

DIGESTION
GLUCOSE HOMEOSTASIS (insulin/glucagon)

Exocrine, Endocrine, ductal cell types

Question 6

What 4 cell types in the islets of langerhans of the endocrine pancreas?

Answer 6

1. Alpha- glucagon (15-20%)
2. Beta- INSULIN (60-80%)
3. Gamma- Somatostatin (5-10%)
4. PP-cells - Pancreatic polypeptide (15-20%)

Question 7

3 beta cell functions

Answer 7

synthesize, store, regulate INSULIN

Question 8

Synthesis of Insulin
Describe the 6 steps of how its made
from transcription->prepro>pro>insulin + c pep

Where it happens and what is modified

Answer 8

1st. Beta cell gene for insulin is transcribed into mRNA in the nucleus
2. mRNA code for insulin is transported to RER in Cytosol
3. N-terminal signal penetrates RER and insulin is made/injected into the lumen of RER as pre-pro-insulin
4. Pre-pro-insulin is cleaved and now Pro-insulin
5. Pro-insulin is transported to the golgi where it is cleaved and forms Insulin and C-Peptide
6. Insulin and C peptide are secreted in secretory vessicles via exocytosis

Question 9

What does PDI & Chaperone do? (Protein Disulfide Isomerase)

Answer 9

Helps correct folding of pro-insulin and forms the disulfide bonds in the RER

so that it can be transported to the Cis golgi for cleavage into insulin and Cpeptide

Question 10

Where is 3 places glucagon made?

Answer 10

Alpha cells of the endocrine pancreas (outside perimeter)

AND

L-Cells of Intestines

(some in brain too)

Question 11

What are incretins? Where are they synthesized?

Answer 11

GI hormones released in response to meal w/ carbs

Insulin-secretion-stimulating agents

made during the post-translational processing of
pro-glucagon

(when it is made by intestinal L-Cells)

Question 12

What is GLP-1?

Where does it come from?

Answer 12

GLP1 is created during post-translational processing of the glucagon from LCELLS.

L-Cells secrete glucagon in the small intestines (colon-ilium)
undergo post-processing and incretins are made as a result.

Question 13

What does GLP-1 do?

Answer 13

LOWERS BLOOD GLUCOSE LEVELS by:

Stimulating insulin and inhibiting Glucagon release

Increases the IG ratio

Question 14

What is GLP-1 degraded by? how fast?

Answer 14

-GLP1 degraded by DPP-4 (dipeptidyl peptidase-4) within minutes

Question 15

What is responsible for increasing the IG ratio after a carbohydrate rich meal?

Answer 15

INCRETIN GLP1 released by the L-cells of the small intestines (colon and ilium) minutes after eating a meal

prepares the pancreas for the nutrient load to enter the blood

Question 16

What type of drugs are used to treat diabetes mellitus?

Answer 16

Incretin mimetic drugs:

EXENATIDE (Byetta)- GLP-1 mimetic, resists degradation by DPP-4 w/ long half life (12 hours).

Mimetic drugs resemble incretins- which are decreased in diabetes mellitus patients

Question 17

What is Exenatide (Byetta)?

Answer 17

GLP-1 Incretin mimetic drug used to treat diabetes mellitus

-long half-life (12 hours) by resisting degradation by DPP-4

Question 18

What are secretagogues?

Answer 18

Insulin is stored in secretory granules and secretagogues initiate release of insulin upon being signaled

Question 19

What does Glucokinase do?

Answer 19

Converts Glucose to G6P inside the cell.

Once G6p, glucose is STUCK inside the cell

Question 20

Describe how beta cells Detect blood glucose

Answer 20

Increased [Glucose] > increased ATP/ADP ratio
ATP inhibits (atp sensitive K channel) > DEPOLARIZATION
depolarization> CamKinase2 > Exocytosis of INSULIN

Question 21

What is Sulfonylurea? What does it target?

Overall Function?

Answer 21

Sulfonylurea is a secretagogue of insulin release
Targets the atp-sensitive K+ channel

LOWERS BLOOD GLUCOSE LEVELS

(risk of hypoglycemia b/c they act independent of existing blood glucose levels)

Question 22

Type II diabetes (mellitus) can be treated with what drug that acts on atp-sensitive K+ Channels?

Answer 22

Sulfonylurea

blocks K+ channel causing a depolarization and release of insulin (independent of current blood glucose levels)

Question 23

What is the first pass effect?

Answer 23

Blood pancreas to portal vein into liver (50-60% IG) metabolized before hitting systemic circulation.

Question 24

how long is half life of IG?

Why?

Answer 24

3-5 minutes

50-60% metabolized in liver (first pass effect)
Kidney degrades 1/2 of systemic IG
Proteases destroy IG in systemic circulation

Question 25

If IG has such a short half-life, its unreliable to use as a determining factor of diabetes. What Should you measure to determine levels of Beta-cell activity?

Answer 25

C-Peptide (secreted 1:1 ratio w/ insulin) - not degraded by liver or other organs - HL ~30 min

Question 26

What REGULATES Insulin release? looking for 1 major and 3 minor regulators

Answer 26

GLUCOSE! (almost entirely regulated by glucose) - Epinephrine (stress hormone)- Inhibits Insulin Release - incretins help release insulin (GLP1) - AA's stimulate insulin in absence of glucose

Question 27

What is a counter-regulatory hormone? | What 4 are the counter-regulatory hormones ?

Answer 27

Hormones that oppose the action of insulin on glucose: Glucagon, Epinephrine, Cortisol, growth hormone

Question 28

How does epinephrine affect Pancreatic Beta Cells?

Answer 28

- promotes fuel mobilization during stress, exercise, and fasting) Epinephrine (stress hormone) DECREASES/Inhibits INSULIN

Question 29

How does epinephrine affect Pancreatic Alpha Cells?

Answer 29

Alpha cells produce GLUCAGON (increase blood glucose) | Epinephrine (stress hormone) INCREASES Glucagon and blood glucose

Question 30

How do Dietary amino acids affect alpha and beta pancreatic cells?

Answer 30

CAN INCREASE BOTH insulin and glucagon secretion... ? Why? If there is no carbs in the diet, (PROTEIN ONLY DIET- ATKINs) - we use AA's to make glucose

Question 31

Glucose uptake is insulin-dependent in many tissues of the body (brain, RBC, intestine, cornea, kidney, liver) What tissues REQUIRE Insulin/Glucagon for glucose uptake? What transporter expressed on these cells?

Answer 31

MUSCLE & ADIPOSE Insulin-dependent GLUT-4 TRANSPORTER

Question 32

Muscle and Adipose are unique in that they require Glucose transporters to take up glucose. Describe what signals initiate what transporters to get glucose into the cell.

Answer 32

1. Insulin stimulates endosome to release GLUT4 transporter 2. GLUT4 fuses with cell membrane of muscle/adipose and glucose is taken into the cell 3. GLUT4 reabsorbed into endosome when insulin levels fall

Question 33

General Fed state (charging mode)

Answer 33

High IG Fuel storage (make TAGs, glycogen, proteins) Use Glucose as energy source Glucose uptake (GLUT4)

Question 34

General Fasting State (battery mode)

Answer 34

- Low IG - Battery Power (TAGs, Glycogen, Proteins) - Use FA's and Ketone Bodies for energy (except RBC and Brain- Always use glucose) - Glucose synthesis in liver for export (for brain & RBC)

Question 35

Where does Lipolysis Take Place? | Where does Beta Oxidation take Place?

Answer 35

ADIPOSE TISSUE_ NOT THE LIVER!!!! Beta oxidation takes place in the liver

Question 36

How much glucose does the brain require per day? | How much required for total body per day?

Answer 36

Brain requires 130grams glucose/ day Total body requires 180grams glucose /day 72% of total required glucose is used by the BRAIN!!!

Question 37

If we eat atkins Protein only Diet | where does glucose come from?

Answer 37

Low IG ratio: small insulin release prevents muscle protein degradation, but not the rest of fasting responses Synthesize glucose from scratch but uses dietary AA's

Question 38

LONG TERM FASTING

Answer 38

Muscles degrade to make glucose from scratch

Question 39

What type of cell does glp1 work on?

Answer 39

Beta cell - helps release insulin

Question 40

Which does what? Insulin/Glucagon phosphorylate/dephosphorylate target enzymes?

Answer 40

INSULIN- Dephosphorylates target enzymes GLUCAGON- phosphorylates target enzymes