T1 L14:Drug treatement of Type 2 Diabetes

Question 1

what tissues does insulin target

Answer 1

liver

adipose

skeletal muscle

Question 2

advantages of metformin

Answer 2

cheap

effective

safe-least side effects

Question 3

what does insulin do to the hepatic cells (processes)

2m

Answer 3

Decreases:
gluconeogenesis, glycogenolysis, ketogenesis,

(increases glycogen synthesis)

Question 4

what & how do muscle cells do to respond to insulin

3m

Answer 4

decreases- glycogenolysis & amino acid release

increases GLUT-4 translocation to the membrane and hence increase glucose uptake, glucose oxidation, glycogen synthesis, amino acid uptake, protein synthesis

Question 5

what do adipocytes do in response to insulin

Answer 5

increase glucose uptake, increase triglyceride synthesis; decrease FFA and glycerol release

Question 6

what is the net effect of insulin

Answer 6

is to cause hypoglycemia

and increase fuel storage in muscle, fat tissue and liver

Question 7

what happens to the insulin sensitivity and insulin conc from a normal to a t2 diabetic

Answer 7

usually, insulin sensitivity is high and insulin conc is low.

Both decrease in t2 but reverse as well- high resistance and low insulin conc

Question 8

what causes hyperglycaemia

Answer 8

Renal glucose absorption

Loss of beta-cell mass

Insulin resistance

Question 9

what is an example of a sulfonylureas

when are they active, and what are they bound to and %

Answer 9

Gliclazide

glipizide

orally active

90-99% bound to plasma protein

Question 10

What is the primary mechanism of how sulfonylureas act

Answer 10

• stimulates endogenous insulin release
• binds to ATP-sensitive-K-channel, inhibiting cell opening to ATP
• causing beta cells to depolarise and ca influx and insulin release

-

Question 11

what are the secondary mechanisms of how sulfonylureas work

Answer 11

Sensitize ß-cells to glucose

Decrease lipolysis

Decrease clearance of insulin by the liver

Question 12

who is sulfonylureas best used on and what is it’s side effects

Answer 12

The best patient-

• over 40 years
• DM duration less than 10 years

Side effect-hypoglycaemia

Question 13

give an example of a biguanide

Answer 13

Metformin

Question 14

what do biguanides do and secondary effects (3m)

Answer 14

increase glucose uptake in muscle and decrease glucose production by liver (Increasing insulin sensitivity via):

• Enhances peripheral glucose uptake
• –Increased GLUT 4 translocation through AMPK

-Increases fatty acid oxidation via decreasing insulin-induced suppression of fatty acid oxidation

Question 15

what is the mechanism of action of biguanides

Answer 15

It reduces hepatic glucose production:

via AMP-activated protein kinase (AMPK) dependent and independent pathways

AMPK increases expression of the nuclear transcription factor SHP which in turn inhibits the expression of hepatic gluconeogenic genes. ie G-6-P glucose-6-phosphatase

Question 16

what other properties of metformin is peculiar (3)

Answer 16

• orally active
• does not bind plasma proteins
• often combined in a single pill with other anti-diabetic medications

Question 17

what other syndrome can metformin treat

Answer 17

also used for polycystic ovary syndrome

Question 18

when can you not use metformin

Answer 18

hepatic disease

past history of lactic acidosis (any cause)

cardiac failure

Question 19

Give an example of a Glitazones (thiazolidinediones

Answer 19

Pioglitazone-

Question 20

how does Pioglitazone function

3m

Answer 20

Activate peroxisome proliferator-activated receptor-g (PPARg)

(involved in involved in transcription of insulin-responsive genes and in regulation of adipocyte lipid metabolism)

Question 21

what does pioglitazone cause

and what does it need to work

Answer 21

It needs the presence of endogenous or exogenous insulin to:

• decrease gluconeogenesis, glucose output, and triglyceride production in liver
• increase glucose uptake and utilization in skeletal muscle
• Cause differentiation of adipocytes

Question 22

what are the adverse effects of pioglitazone

Answer 22

interactions due to liver metabolism.

weight gain

fluid retention

Question 23

what is a major advantage of Glucagon-like peptide-1 analogs GLP-1

Answer 23

It increases satiety and reduces food intake

Question 24

give an example of a GLP-1

Answer 24

Exenatide

Question 25

how does exenatide work

4m

Answer 25

• Augmenting pancreas response
• Suppresses pancreatic release of glucagon helping stop the liver overproducing glucose
• Slows down gastric emptying
• Reduces appetite and promote satiety via hypothalamic receptors

Question 26

what is a DPP-4 inhibitor stand for

Answer 26

Dipeptidyl peptidase-4

Question 27

what is DPP-4 inhib its mechanism and results

Answer 27

Class of oral hypoglycaemic agents

Mechanism of action is through increased Incretins GLP-1 and GIP

Increased incretins cause:
-Inhibit glucagon release

• Increase glucose-induced insulin secretion
• Decrease gastric emptying

Question 28

Give an example of a DPP-4 inhibitor

Answer 28

vildagliptin

Question 29

what is an SGLT drug -

Answer 29

Sodium-glucose transporter protein inhibitors

Question 30

where does it act

Answer 30

SGLT-2 receptor

has high capacity and low affinity

Found in PCT

causes glucose to be excreted by kidneys through the urine

Question 31

overall effects of SGLT-2 are

Answer 31

Increased insulin sensitivity

Improved beta cell function

decreased gluconeogenesis