Diabetes

Question 1

Type one initiation?

Answer 1

Up regulation of IFN alpha

Which stimulates cytotoxic Tcells

Up regulation of MHC class 1 enables cytotoxic T cells to attack

Question 2

TCell attack

Answer 2

Beta cells become available due to apoptosis and the antigens are then displayed to the autoimmune system which creates antibodies

Question 3

CD8 cytotoxic T cells

Answer 3

Attack the beta cells and bind the cell receptors causing apoptosis as the fasl bind the gas on the B cell

Question 4

CD4

Answer 4

Present the Antigen receptor on the surface causing the B cell to release cytokines such as TNF alpha which induces apoptosis on other beta cells

Question 5

Autoimmune diseases

Answer 5

Generally occur when an issue with the Tcell suppression cells, auto reactive cells

Question 6

Process of increasing autoantibodies

Answer 6

Increased production of IFN before MHC1 increases as well then CD8 binds eating the beta cells before the antigen from the beta cells are transported

Can be extended when CD8 binds and destroys periforin and the process repeats

Question 7

Time of diagnosis in T1

Answer 7

8years

Question 8

Type 2

Answer 8

Insulin sensing and signalling

Question 9

Glucose induced secretion

Answer 9

Glut1 allows glucose into the cell and glucokinase causes its metabolism releasing ATP to close the k channel and sends PDX1 to the nucleus to increase production of insulin and calcium channel opens causing the release of insulin from its capsules

Question 10

Incretin and glucose induced secretion

Answer 10

GLP1 released when glucose is sensed in the gut and binds the receptor on the B cell increasing camp levels and then PKA and epac2 converge on the exocytosis path increasing insulin secretion

Question 11

Glucose kinase mutation

Answer 11

Loss of metabolism as glucose cannot be metabolised

Question 12

Kcnd11 abbc8

Answer 12

Loss of function mutations in the k channel so it cannot be closed

Question 13

PDX1 mutation

Answer 13

Lethal so no cases present as no insulin at all can be transcribed as its a TF for islet cell or birth

Question 14

Insulin receptor

Answer 14

TRK docking to IRS1 which activates pi3 kinase which the catalysed the phosphorylation of pip2 converting it to pip3 which activates akt which catalysed phosphorylation of key proteins such as glycogen synthase

Question 15

Non receptor mutation

Answer 15

The serine is phosphorylated on IRS as opposed to the tyrosine

Question 16

CDKAL1

TCF7L2

Answer 16

Risk alleles associated with low and high birth weight both leading to potential t2

Question 17

Type 1

Answer 17

Destruction of beta cells

Genetic susceptibility

Question 18

ROS

Answer 18

At least six main pathways contribute to them

Islet cells have worst chance as they have low number of antioxidants in them

Question 19

Increased glucose

Answer 19

Means more production of acetyl co enzyme A and oxaloacetate which cause increased oxidative phosphorylation increasing ROS

Question 20

Islets at risk

Answer 20

Due to low levels of sod 12

Question 21

Adipocytes

Answer 21

Lean state stores fat as triglycerides

Excess calories leads to metabolic overload and enlargement

Further intake causes hyper trophy and they release cytokines (mcp1) which recruits macrophages

Question 22

Adipose inflammation pathway

Answer 22

Macrophage attracts by mcp1 which secretes TNF causing chronic inflammation and the excess free fatty acids inhibit glucose uptake

Question 23

Ketoacidosis

Answer 23

T1

Fatty acids converted into ketones

Question 24

Glycation metabolism

Answer 24

Glycation and protein damage

Question 25

Glyceradehyde autoxidation

Answer 25

Hydrogen peroxide and alpha ketoaldehydes

Question 26

Treatment for type 1

Answer 26

Insulin therapy Transplantation Prevention of autoimmunity

Question 27

T1 insulin treatment

Answer 27

Injects insulin at continuous basal level

Question 28

Autoimmunity treatment t1

Answer 28

Immune supresives e.g methotrexate Anti inflammatory e.g aspirin or NSAIDs T cell inhibitors e.g sirolimus Best would be a cd8 inhibitor

Question 29

Transplants t1

Answer 29

Pancreas to people who need new kidneys Islets to achieve normoglycemia

Question 30

Type 2 therapies

Answer 30

Sensitisers Secretagogues Glucosidase inhibitors

Question 31

Glucosidase inhibitors

Answer 31

Acarbose inhibits production of glucose from oligosaccharides Side effects are standard

Question 32

Insulin sensitisers

Answer 32

Rosiglitizone activate ppar increasing transcription of insulin sensitive genes but have been taken of market Metformin ampk agonist increasing sensitivity and reducing hepatic glucose production

Question 33

Secretagogues

Answer 33

Meglitidines inhibit k channels so it stays shut Byetta GLP1 agonists DPP4 inhibitors prolong the activation of of beta cells

Question 34

SGLT inhibitors

Answer 34

Located in the kidneys Dapagliflozin causes excess glucose to be eliminated n the urine