Introduction to Diabetes Mellitus: Insulin action (5)

Question 1

What effect does insulin have on glucose

Answer 1

it decreases hepatic glucose output and increases uptake of glucose by muscles

Question 2

What effect does insulin have on protein

Answer 2

it decreases proteolysis (breakdown of protein)

Question 3

What effect does insulin have on lipids

Answer 3

it decreases lipolysis and decreases ketogenesis

Question 4

What other effects does insulin have

Answer 4

growth, vascular effects, ovarian function, clotting and energy expenditure

Question 5

what transporter is glucose uptake through

Answer 5

Glucose Transporter 4 (GLUT 4)

Question 6

Where is GLUT 4 particularly abundant

Answer 6

in muscle and adipose tissue

Question 7

What stimulates GLUT 4

Answer 7

insulin

Question 8

Describe the structure and location of GLUT 4 in cells

Answer 8

It has hydrophobic elements on the outside embedded in the membrane and a hydrophilic core which allows glucose into the cell. GLUT-4 sits in vesicles within the cytoplasm

Question 9

How does insulin cause a 7 fold increase in glucose uptake

Answer 9

insulin recruits GLUT 4 to the membrane. they are insulin responsive

Question 10

What does cortisol do in muscle cells when we are stressed

Answer 10

increase proteolysis

Question 11

what effect does insulin have on amino acids in muscle cells

Answer 11

prevents the oxidation of them and increases the re-synthesis of proteins from amino acid

Question 12

what are gluconeogenic amino acids

Answer 12

amino acids that have entered the circulation and moved to the liver where they are used to produce glucose

Question 13

how do gluconeogenic amino acids enter the liver

Answer 13

via specific transporter channels.

Question 14

what increases the uptake of amino acids into the liver

Answer 14

glucagon

Question 15

what does insulin stimulate in the liver

Answer 15

protein synthesis

Question 16

What increases gluconeogenesis in the liver

Answer 16

Somatotrophin, Cortisol, Catecholamines and Glucagon

Question 17

What inhibits gluconeogenesis in the liver

Answer 17

insulin

Question 18

what is hepatic glucose output (HGO)

Answer 18

glucose produced by gluconeogenesis in the liver that enters the circulation

Question 19

What are triglycerides broken down by before they can enter the adipocyte

Answer 19

lipoprotein lipase stimualated by insulin

Question 20

what is the triglyceride broken down into

Answer 20

glycerol and non esterified fatty acids

Question 21

why does glucose enter the adipocyte

Answer 21

to be used to make NEFA with glycerol and non esterified fatty acids

Question 22

how can glucose be used to make triglycerides

Answer 22

it can be chopped up to make 2 glycerols and the fatty acids can be stuck to the glycerol to make triglycerides

Question 23

what effect does insulin have on fat in the blood

Answer 23

breaks down fats so it can enter the adipocyte

Question 24

what effects does insulin have on fat in the adipocyte

Answer 24

promotes formation on triglyceride and storage of fat and inhibits lipolysis

Question 25

why is waist circumference a simple indicator of an individuals risk of ischaemic heart disease

Answer 25

blood reaches the gut and there is a portal system connecting the intestines to the liver. the blood passes through the liver for the absorbed food to be processed. adipocutes in the gut are different in activity and endocrine regulation compared to the rest of the body

Question 26

what is glycerol from adipocytes and food entering the liver used for

Answer 26

to make triglycerides which then enter lipoprotein particles

Question 27

what can glycerol also be used to make

Answer 27

glucose and this supports hepatic glucose ouput

Question 28

why cant fat do even though glycerol can be used to make glucose

Answer 28

reenter the glucose pathway

Question 29

what happens after a 10 hour fast

Answer 29

25% of our hepatic glucose output is supported by new glucose production

Question 30

what fuel can the brain use and not use

Answer 30

can use glucose and ketone bodies but cannot use fatty acids

Question 31

what can fatty acids made from lipolysis be used to make in the liver

Answer 31

ketone bodies

Question 32

what is the effect of insulin on ketone body synthesis in the liver

Answer 32

it inhibits the conversion of Fatty Acyl CoA to ketone bodies

Question 33

high blood glucose + high ketone bodies =

Answer 33

insulin deficient

Question 34

definition of ketones

Answer 34

three water soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction.

Question 35

what are the three ketone molecules

Answer 35

acetone, acetoacetic acid, beta-hydroxybutyric acid

Question 36

what promotes hepatic glycogenesis

Answer 36

insulin, glucagon and catecholamines

Question 37

what is glucose converted to in the liver

Answer 37

glucose-6-phosphate

Question 38

what are the 2 processes that support hepatic glucose output

Answer 38

gluconeogenesis and glycogenolysis

Question 39

what promotes uptake of glucose by GLUT-4

Answer 39

insulin

Question 40

what inhibits uptake of glucose by GLUT-4

Answer 40

stress hormones - GH, CATS, CORT

Question 41

what is glucose stored as in muscle cells

Answer 41

glycogen

Question 42

characteristics of the fasted state

Answer 42

low insulin : glycogen ratio. normal blood glucose concentration due to the change in ratio. muscle uses lipid. brain uses glucose and then at a later stage ketone bodies

Question 43

what is there an increase of in the fasted state

Answer 43

concentration of NEFA, proteolysis, lipolysis, hepatic glucose output

Question 44

what is there a decrease of in the fasted state

Answer 44

amino acid concentration when prolonged

Question 45

characteristics of the fed state

Answer 45

high insulin:glucagon ratio. stored insulin released then you get 2nd phase insulin release. stop hepatic glucose output

Question 46

what is there an increase of in fed state

Answer 46

glycogen, protein synthesis and lipogenesis

Question 47

what is there a decrease of in fed state

Answer 47

gluconeogenesis, proteolysis

Question 48

presentation of type 1 diabetes mellitus

Answer 48

Absolute insulin deficiency. Proteolysis with weight loss. Hyperglycaemia. Glycosuria with osmotic symptoms. Ketonuria

Question 49

Insulin induced hypoglycaemia causes an increase in:

Answer 49

insulin, glucagon, catecholamines, cortisol and somatotrophin, HGO and lipolysis

Question 50

What is insulin induced hypoglycaemia and how is it treated

Answer 50

Treatment induced complication. Increased insulin from SUBCUTANEOUS stores --> glucose uptake into muscle --> low plasma glucose concentration. TREATMENT: Increased INTRAMUSCULAR glucagon --> increased HGO, Glycogenolysis and gluconeogenisis and increased lipolysis --> increased plasma glucose

Question 51

Insulin resistance and its effects

Answer 51

It resides in the liver, muscle and adipose tissue. Increase in LDL (dyslipidaemia), circulating NEFA, triglyceride. decrease in lipoprotein lipase activity, VLDL clearance and HDL cholesterol.

Question 52

in T2DM what is there enough insulin to suppress

Answer 52

ketone production and proteolysis

Question 53

what 2 pathways does insulin have an effect on

Answer 53

mitogenic pathway (MAPK) and metabolic pathway (PI3K-Akt)

Question 54

compensatory hyperinsulinaemia

Answer 54

someone with insulin resistance makes enough insulin to maintain normal blood glucose

Question 55

features of insulin resistance

Answer 55

hypertension (BP>135/80), high triglyceride, high ldl, fasting blood glucose > 6.0mmol/L, adipocytokines, inflammatory state, energy expenditure, large waist circumference

Question 56

presentation of T2DM

Answer 56

Insulin resistance. 60-80% obese. Dyslipidaemia. Later insulin deficiency. Hyperglycaemia. Less osmotic symptoms. With complications

Question 57

management of T2DM by controlling diet

Answer 57

Control total calorie intake. reduce fat, refined carbohydrate and sodium. increase complex carbohydrate and soluble fibre