Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Intercal - Adaption in physiology > Diabetic Adaptation 1 > Flashcards

Diabetic Adaptation 1 Flashcards

1
Q

What is a normal fasting glucose

A

4-5.9mM - maintained by glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a normal feeding glucose

A

7.8mM - dropped by insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does insulin lower blood glucose

A

Drops glucose production by liver
Increases glucose uptake in adipose (to make more fat) and skeletal muscle (for energy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give some positive actions of insulin

A

Glucose uptake
glycolysis
Glycogen synthesis
Protein synthesis
Ion uptake (K)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give some negative actions of insulin

A

Gluconeogensis
Glucogenolysis
Lipolysis
Ketogenesis
Proteolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Define diabetes mellitus

A

Metabolic disease characterized by hyperglycemia resulting in defects in insulin secretion due to beta cell destruction (DM1) or insulin resistance (DM2) or both.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is associated with diabetes type 2

A

Obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How was insulin discovered

A

Minkowski removed pancreas of dog in 1899 which caused symptoms of diabetes

1921 - banting, best and macleod made an extract of the pancreas and cured dog by injecting back into pancreas

Cured boy in 1922 with DM1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What causes ketoacidosis

A

Anti-lipolytic effect of insulin is lost resulting in increase of serum free fatty acids into ketones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why does diabetes cause CVD

A
  • Chronic low grade inflammation due to dyslipidemia and hyperglycaemia
  • Hypertension and endothelial dysfunction due to nitric oxide decrease
  • Both causing –> Atherosclerosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is insulin found

A

Preformed granules in beta cells to allow insulin release at any time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is PDX1 (pancreatic and duodenal homeo-box 1)

A

A transcription factor that is required for all stages of pancreatic B cell development and mature B cell function and survival

Required for all stages of B cell function and maturation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is FoxA2/HNF3-beta

A

Works with PDX1 and acts as a pioneer factor to regulate PDX1 gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is MafB

A

Required in late development after PDX1 and FoxA2 but is not present n the mature B cell.
Restricted to adult alpha cells - glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is MafA and its role

A

Found exclusively in developing and adult Beta cells. Required for -

  • Structure of islets
  • Ratio of B cells: A cells
  • Glucose stimulated insulin secretion
    Gene expression of
  • Glut2 - beta cell glucose transporter
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where does glucagon act

A

On liver for glycogenolysis (glycogen break down into glucose) and gluconeogenesis (make more glucose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What regulates glucose release

A

Glucose-6-phosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does glucose enter the beta cell

A

Glucose entering the beta cell via glut2 transporters (high Km - no matter how high glucose conc goes it can keep transporting).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What happens to glucose inside the cell

A

Converted to glucose-6-phosphate by glucokinase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What happens to G-6-P

A

Glycolysis and mitochondrial metabolism causing an increase in ATP/ADP ratio.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What 2 things does a rise in this ATP/ADP ratio do

A

Depolarise cell –> which releases insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does cell depolarisation release insulin

A

The ATP/ADP ratio leads to activation of the sulphonylurea receptor 1 (SUR1) protein

Lead to closure of the adjacent potassium ATP channel (potassium inward rectifier [KIR] 6·2 channel).

The closure of the potassium channels will alter the membrane potential and open calcium channels.

This triggers the release of preformed insulin-containing granules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the 2 roles of GLUT2

A

Glucose stimulated insulin secretion from beta cells of pancreas islets.
Controls entry and exit of glucose in liver.

24
Q

What is the role of GLUT4

A

An insulin RESPONSIVE glucose transporter.

Found in heart, skeletal, muscle, adipose tissue and brain to uptake glucose.

25
Q

On a molecular level, what causes type 2 diabetes

A

Results from impaired insulin secretion caused by failure of the beta-cell K ATP channel to close in response to increased intracellular ATP.

26
Q

How do sulfonylureas treat type 2 diabetes

A

Close the K ATP channel by an ATP-independent route.

27
Q

What SNP has been noted in DM2

A

In the KCNJ11 and ABCC8 genes which code for the sulfonlyurea protein and K ATP channel. this single nucleotide polymorphism limits insulin release

28
Q

What happens with a KO of the KCNJ11 gene in mice
Koster 2000

A

Causes overactive K ATP channel and therefore develops severe hyperglycemia with hypoinsulinaemia and severe ketoacidosis.

29
Q

What did pearson et al in 2006 discover about Kir6.2 mutaitons

A

Switched patients to sulfonlyureas for better response.

30
Q

What is the role of incretin hormones

A

Released from gut during digestion and can enter bloodstream and regulate beta cell function

31
Q

Give 2 examples of incretin hormones

A

GLP-1
GIP

32
Q

What do DPP4 inhibitors do (sitagliptin)

A

Drug that can break down DPP4 and increase GLP-1 as DPP4 is a GLP-1 inhibtor.

33
Q

What stimulates GLP 1

A

Glucose, fatty acids, amino acids

Vagus nerve, insulin

34
Q

What inhibits GLP-1

A

Somatostatin

35
Q

What is the main purpose of incretins

A

To increase intracellular calcium in beta cells which therefore triggers more insulin release

36
Q

Where do incretins bind

A

G protein coupled receptors to act on adenylyl cyclase

This activates cAMP which increases PKA and Epac

Which increases intracellular calcium levels and in turn increase insulin release

37
Q

Is GLP-1 secretion deficient in diabetics

A

No, not in any state - Baltimore longitudinal study of aging.

38
Q

What is exenatides/liraglutide role

A

GLP-1R agonist/GLP-1 analogs.

39
Q

How do tyrosine kinase receptors work

WIDER READING – Saltiel 2001

A

Have two alpha and two beta subunit which function as allosteric enzymes where the alpha subunits inhibit the activity of the beta subunits.
This inhibition of Beta subunits causes transphorylation of these subunits which lets the receptor undergo conformational change and increase activity.

40
Q

How are GLUT4 vesicles excytosed when insulin binds

WIDER READING – Pessin 1999

A

Unknown but believed to be a microtubule network

41
Q

What protein is important in GLUT4 docking

WIDER READING – Pessin 1999

A

v-SNARE protein – VAMP2 interacts with syntaxin 4 on GLUT4 vesicles during docking and allows fusion to the plasma membrane.

42
Q

What happens with a cre-loxP conditional gene knockout of GLUT4 if the muscle of mice

WIDER READING – KIM et al 2000

A

Have normal glucose tolerance as a shift of the excess glucose is uptaken in the fat causing an increase in adipose tissue mass and circulating free fatty-acids and triglycerides.

43
Q

What happened with V cells Specific insulin receptor knockout in pancreas and brain-specific insulin knockout in brain occurred

WIDER READING – Bruning et al 2000

A

Defect in glucose stimulated insulin release and an increased food intake ability with mild adiposity. Showing that insulin resistance in the B cell and other body tissues combine to produce the pathophhsiology of DM2

44
Q

In those with diabetes that are insulin deficient, what was found to be their most common complication
WIDER READING – Ahlqwist 2018

A

Diabetic retinopathy – shows the vast complexity and varied presentation of those with diabetes.

45
Q

In those with diabetes that are insulin resistant what was found to be their most common complication
WIDER READING – Ahlqwist 2018

A

Diabetic nephropathy – shows the vast complexity and varied presentation of those with diabetes.

46
Q

How does excess fat cause insulin resistance
WIDER READING – Kamei et al 2006

A

Adipocytes secrete chemokine MCP-1 which drives macrophage accumulation into adipose tissues and this induces insulin resistance in them.
Confirmed with MCP-2 knockout in mice improves insulin sensitivity in mice – Kanda et al 2006

47
Q

What role do toll-like receptors (TLR) have in insulin resistance
WIDER READING - shi et al 2006

A

TLR2 and TLR4 can be activated by saturated fatty acids which indicate that these receptors play a role in obesity driven inflammation. Confirmed with mice as knockout of these TLRs protected from obesity and obesity associated insulin resistance

48
Q

What is the incretin effect
WIDER READING – Nauck 2017

A

A 2-3 fold increase in insulin secretion in response to oral glucose compared to IV glucose which is diminished in type 2 diabetics

49
Q

What happens to the incretin effect in T2DM
WIDER READING – Nauck 2017

A

Diminished or no longer present because of substantially reduced effectiveness of GIP on the diabetic endocrine pancreas.

50
Q

Why is GLP-1 so important in type 2 diabetic Rx
WIDER READING – Nauck 2017

A

GLP-1s insulinotropic and glucagonostatic effects are still present in diabetics and therefore can significantly lower plasma glucose and improves glycaemic control.

51
Q

Other than the effects on blood glucose lowering, what other benefits do GLP-1 provide to diabetics
WIDER READING – Nauck 2017

A

Reduce appetite and food intake  weight loss
Also further backed up by the fact – GLP-1 receptors are found in the hypothalamus

52
Q

What is the role of GIP (incretin) in fat storage and how was it confirmed
WIDER READING – Miyawaki 2008

A

GIP receptor knockout mice don’t develop obesity with hypercaloric feeding
GIP also known to induce lipoprotein lipase – enzyme that releases fatty acids from chylomicron triglycerides in adipose tissue thus promotes the elimination of chylomicron triglycerides
E.g. – GIP believed to promote fat storage in subcutaneous tissue

53
Q

What does GIP receptor knockout do to beta cells
WIDER READING – Campbell 2016

A

Increased apoptosis of them

54
Q

What do mice overexpressing GLUT4 in adipocytes show
WIDER READING – Moraes-vieira 2016

A

Elevated adipose tissue lipogenesis and enhanced glucose tolerance despite being obese

55
Q

What role does TNF-alpha play in obesity-related diabetes and how was this shown.

Wider reading – Gokhan 1994

A

TNF-alpha is a key mediator in insulin resistance – used a rat model for obesity and insulin resistance after neutralzing TNF-alpha and this resulted in a marked increase in insuline stimulated autophosphorylation of the insulin receptor as well as IRS-1 phosphorylation in muscle and fat of these rats restoring them to near lean levels. Also lowered plasma glucose and FFAs.
No effects seen on IRS-1 or IR in the liver.

Shows that – TNF-alpha inhibits the IR tyrosine kinase in muscle and fat which induces obesity-related diabetes.

Intercal - Adaption in physiology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions