Mastick Flashcards Preview

Block 3; Week 2 > Mastick > Flashcards

Flashcards in Mastick Deck (76)
Loading flashcards...
1

What is the problem in Type I Diabetes? What type of defect is it? What are the levels of insulin like? What is the treatment?

autoimmune destruction of beta cells
primary defect
there is no insulin!!
Treatment: insulin injections required or islet transplant

2

What is the problem in Type II Diabetes? What type of defect is it? What are the levels of insulin like? What is the treatment?

beta cell exhaustion-->compensation for insulin resistance
secondary defect
not enough insulin or maybe even high levels, but resistance
Treatment: oral hypoglycemia

3

What is the predicted transition in 2025 in terms of our issue w/ Diabetes?
What does this really mean?

Transition from diabetes epidemic to Diabetes tsunami...
this means that a higher percentage of the population is becoming diabetic...

4

What are some important complications of Diabetes?

heart disease & stroke
hypertension
blindness
kidney disease
nervous system disease or neuropathy
amputations (non-traumatic)

5

T/F the pancreas is highly innervated (by parasymp & symp) & highly vascularized.

TRUE

6

What are the 2 main divisions of the pancreas?

Pancreatic Acini: secrete digestive juices into the duodenum
Islets of Langerhans: secrete insulin & glucagon into the blood

7

What separates the acini from the islets?

CT capsules

8

What are the 3 cells that make up the islets of Langerhans & what is their prevalence & what do they secrete?

Alpha cells; 25%; secrete glucagon
Beta cells; 60%; secrete insulin & amylin
Delta cells; 10%; secrete somatostatin

9

What are the functions of the following?
Insulin
Glucagon
Somatostatin

Insulin: anti-hyperglycemic (glucose clearance)
Glucagon: anti-hypoglycemic (glucose secretion)
Somatostatin: tonic modulator

10

What does it mean that somatostatin is a tonic modulator?

It means that glucose homeostasis could maybe be achieved w/o somatostatin...but it's possible that larger & larger levels of insulin & glucagon would build up (in proper proportion). Somato keeps that from happening!! : )

11

What is the blood glucose level kept at in glucose homeostasis?

5.5mM

12

Glucagon, Insulin & somatostatin are all 3 ______ ______. They all begin in the ____ form. What does this mean?

3 peptide hormones
begin in the preproform.
The pre form means that you get across the ER & into the inside of a vesicle for secretion...

13

What is different about the way that proglucagon is broken up in intestinal cells?

The breakdown in intestinal cells releases incretins...

14

How does insulin begin? What is its status once it is at the vesicle?

Begins as preproinsulin. It is proinsulin by the time that it is secreted.

15

What are some important characteristics of proinsulin?

It has a C peptide as a part of it that is later cleaved...it is there to help with folding...
As far as secretion goes...C peptide & insulin are secreted in a 1:1 ratio...
However, C peptide isn't degraded as quickly...so it can help indicate how much insulin has been secreted.

16

What is the relationship b/w the insulin, glucagon, & somatostatin in the human pancreas?

They work together & are all found intercalated & communicating.
Not as much the case in the mouse pancreas.

17

T/F The blood glucose levels remain relatively constant even during prolonged fasting or starvation.

TRUE.
even after 42 days of fasting!!

18

Describe the 4 phases of glucose homeostasis during fasting.

Phase 1 (0-4hrs): well fed-->glucose from diet
Phase 2 (4-16hrs): post-absorptive-->glucose from glycogen stores in the liver & muscles
Phase 3 (2-7days): Early Gluconeogenic-->from gluconeogenesis
Phase 4 (7-42days): prolonged fasting or starvation-->from gluconeogenesis

19

According to the 4 phases of glucose homeostasis...when does the body start using ketones to supply the brain?

Phases 3 & 4
takes around 10-14 days

20

What are 2 ketone bodies that the body can use for fuel?

acetyl acetate
beta-hydroxybutyrate

21

T/F most of the time the blood sugar remains stable & doesn't drop into hypoglycemia.

TRUE

22

What are some people groups that are at risk for hypoglycemia?

Diabetes patients w/ insulin but w/o food
People w/ insulin-producing tumors
Newborns w/ untreated galactosemia
Alcohol-poisoned people
People w/ liver diseases
Athletes who totally exceed their capacity.

23

What can happen progressively if you do experience hypoglycemia?

Faint
Coma
Death

24

What is considered the range that is normoglycemic?

4.5-8.

25

What is the oral glucose tolerance test?

It is a test for Diabetes. Patients are given a bunch of sugar & you observe their blood glucose levels to see if they get a sustained & crazy spike over 200mg/dL.
Shows if that insulin is working...

26

What happens to a patient in the case of hyperglycemia?

nothing really at first, but with chronic exposure the following can happen:
Blindness
Kidney Disease
Nervous System Disease (neuropathy)
Amputation

27

What do glucagon & insulin typically do in response to a meal?

Insulin will increase dramatically.
The glucagon will probably only decrease slightly, if at all...it is relatively constant.
The insulin/glucagon ratio does change, however. You should think in terms of that! : )

28

What does a high protein meal do to insulin & glucagon?

It significantly increases both insulin & glucagon.

29

What does glucagon do between meals?

Glucagon stimulates the liver to release glucose (glycogenolysis) & keeps the blood glucose around 4.5.

30

T/F Glucagon receptors are found in the muscle, liver, & adipose tissue.

FALSE.
Glucagon receptors are only found in the liver.

31

What happens first...glycogenolysis or gluconeogenesis?

Glycogenolysis

32

During an overnight fast, what happens to the following:
glycogen synthesis
lipolysis
lipogenesis

Glycogen synthesis is inhibited.
Lipolysis is stimulated.
Lipogenesis is inhibited.

33

If glycogen synthesis in muscle tissues is inhibited...what does that do to the amount of glucose required from the blood?

It decreases it. The muscles don't need their glucose supplied by the blood.

34

During fasting, what happens to the resting glucose transport?

It is decreased 3-4 fold relative to the fed (insulin high) state.

35

Even if your insulin isn't high or your insulin isn't helping you (Type II D)...what is another way to accomplish glucose uptake by tissues?

Glucose uptake can be stimulated by exercise. When exercising & muscles use up their glycogen...AMP increases & activates the AMPKinase. This can then accomplish more glucose uptake.

36

Glucose transport into adipocytes is very low/high in basal adipocytes.

VERY LOW

37

T/F It takes a LOT of insulin to inhibit the breakdown of fat in adipose tissues.

FALSE It doesn't take much insulin to inhibit the breakdown of fat.

38

After a meal...the blood glucose increases & insulin is released. What are the 3 main target tissues for insulin where it increases glucose transport? What is the main target?

Liver
Fat
Muscle***most of it goes here!!

39

What happens in a fed metabolic state in the liver?

glycogenolysis inhibited
gluconeogenesis inhibited
lipolysis inhibited
glycogen synthesis stimulated

40

What happens in a fed metabolic state in the muscles?

The rate limiting & important step for Diabetes patients (glucose transport increases 4 fold).
Glycogen synthesis stimulated
Glycogenolysis inhibited

41

T/F Lipogenesis is rate limited by glucose transport into adipocytes.

True.

42

T/F Low insulin levels increases glucose transport 20-50 fold in adipocytes.

FALSE
High insulin levels...

43

When you exercise...what happens in terms of the muscle & AMPK?

Muscle needs more glucose & uses up its glycogen stores. AMPK activated.
Then it increases its glucose uptake.
This decreases the blood glucose levels.
Glucagon relatively increases & insulin decreases.

44

When glucagon is dominating & there is movement toward free glucose...which enzyme is activated? What is the phosphorylation situation?

PKA is activated
The enzymes that break down are phosphorylated & activated.
The enzymes that build up are phosphorylated & deactivated.

45

When insulin is dominating & there is movement toward stored glucose...which enzyme is activated? What is the phosphorylation situation?

PP1
The enzymes that build up are dephosphorylated & activated.
The enzymes that break down are dephosphorylated & inactivated.

46

How does glucose enter a cell?

Thru GLUT transporters. These are bidirectional pores. They just allow glucose to flow down its concentration gradient.

47

What happens as soon as glucose is transported into the cell?

It is phosphorylated & trapped. (by either hexokinase or glucokinase).
This means that there is no free glucose lying around the cell.
Glucose-6-phosphate can't exit thru the GLUT transporters.

48

What is something special about the liver that is different than other cells? In terms of trapping glucose...

Well...normally G-6-P can't get thru GLUT. But in the liver there is also Glucose-6-Phosphatase present, so that it can remove the extra phosphate & allow it to get back thru the transporter.
This is done during periods of fasting.

49

Which direction does glucose flow thru the GLUT transporter?

Down the conc'n gradient of glucose. If blood glucose under 4mmol/L-->it flows into the cell.

50

Which organ expresses the GLUT transporters with the highest affinity? Why is this important?

THE BRAIN! B/c the brain needs delivery of a constant amount of glucose.
Has:
Glut 3: highest affinity-->Km=0.4mM

51

Which organs/cells express GLUT transporters with a low affinity?

Liver
Intestine
Pancreatic Beta Cells
**Glut 2; Low Affinity: Km=15mM

52

Which organs express GLUT transporters with relatively high affinity? Glut 4

Heart
Skeletal Muscle
Fat
**Glut 4: High affinity; insulin-regulated; Km=1mM

53

Which organs express GLUT transporters with relatively high affinity? Glut 1

Pancreatic Alpha cells
most other tissues
**Glut 1: High affinity, Km=1mM

54

Explain the process of insulin secretion in pancreatic beta cells.

Glucose enters the Glut 2 transporter (low affinity) of pancreatic beta cells.
The glucose is immediately phosphorylated by glucokinase into G6P & trapped in the cell. It goes thru glycolysis & respiration & increases the ratio of ATP/ADP inside the cell.
The extra ATP inhibits the potassium channel from allowing K+ to exit the cell. The increase in positive charge causes a depolarization that reaches the voltage-gated calcium channel & allows for an influx of Ca++...This stimulates the release of insulin packaged in its safe little vesicles. Enjoy the journey vesicle!

55

What is one of the advantages of beta cells having low affinity & high capacity Glut 2 transporters & phosphorylating enzymes?

B/c of this a small change in glucose causes a significant change in ATP/ADP ratio & insulin secretions...

56

What is the significance of alpha cells having a high affinity?

This means that with normal levels of glucose, there is no change in glucose transport & no changes sensed.

57

T/F There are many ways to control glucagon secretion.

TRUE.

58

What is the main way of controlling glucagon secretion?

thru the levels of insulin...

59

What's the deal with glucose transport in muscle & fat?

It is regulated by insulin. It expresses Glut 4 which is high affinity & low capacity.
The glucose transport is rate limited by the total number of transporters inserted into the plasma membrane.

60

How much does insulin increase glucose transport in fat? in muscle?

Fat: 20-50 fold
Muscle: 3-4 fold
**Muscle can also get glucose transport thru exercise & AMPK.

61

What is released from the pancreas & is considered a tonic modulator? What cell is it released from?

Somatostatin
delta cells

62

What are 2 plans of attack that work on beta cells to increase their insulin secretion?

Sulfonylureas will increase their secretion by acting on K+ channels directly, inhibiting them.
This causes depolarization, opens the voltage-gated calcium channels & allows the vesicles to flee.
Incretins in the intestines bind to the receptors on the beta cell & make it more suspectible to the insulin.

63

Which of the following is considered a secretagogue? Sulfonylurea or incretins?

Sulfonylureas.
All secretagogues act directly on the K+ channel.

64

What do DPP-4 inhibitors do?

They increase insulin secretion by slowing incretin turnover.

65

What are 4 things that can increase insulin secretion?

Sulfonylurea
Other secretagogues
Incretin analogues
DPP-4 inhibitors

66

What are 2 things that can increase insulin sensitivity?

Biguanides (Metformin)
Thiazolidinediones (Avandia)

67

What do biguanides or metformin do? What tissue type do they target?

They activate AMPK. It is an insulin sensitizer. It sort of mimics exercise. It acts on muscle.

68

What do thiazolidinediones (Avandia) do? What tissue type do they target?

They are PPAR gamma activators. They are insulin sensitizers. They act on adipose. These are the ones Mastick developed.

69

What is something that could decrease glucose absorption?

alpha glucosidase inhibitor (Acarbos)
This inhibits intestinal uptake of starch.
It acts on the intestines.

70

Why might sulfonylureas not be a good choice for a late stage Type II Diabetes patient?

Beta cell burnout
It might not be a good idea to stimulate the cell to secrete more insulin when it is already suffering.

71

What are the 3 possible ways that oral hypoglycemics can work?

Increasing insulin secretion
Increasing insulin sensitivity
Decreasing glucose absorption

72

What is an injected hypoglycemic?

a bunch of things that look like insulin/act llke insulin.

73

What are the treatment options for Type I Diabetes?

insulin injections or islet transplants-->NOT oral hypoglycemics.
Remember: the beta cells were destroyed (autoimmune)

74

What are the treatment options for Type II Diabetes?

oral hypoglycemics
if the patient is late stage-->insulin injections
**Remember: these patients are experiencing beta cell burnout.

75

What does a defect in G6P dehydrogenase do?

decreases NADPH & the ability to reduce glutathione

76

Alcoholics are usu deficient in what? This means that which enzyme can't function? What is the result?

Deficient in thiamine
Pyruvate Dehydrogenase can't function
Lactic acidosis & lethargy results...