Introduction to diabetes mellitus

Question 1

Metabolic actions of insulin relating to glucose

Answer 1

Decrease hepatic glucose output (HGO)

Increase glucose uptake in muscle

Question 2

Metabolic actions of insulin relating to proteins

Answer 2

Decrease proteolysis

Question 3

Metabolic actions of insulin relating to lipids

Answer 3

Decrease lipolysis

Decrease ketogenesis

Question 4

What does insulin have mitogenic actions on?

Answer 4

Lipoproteins
Smooth muscle hypertrophy
Ovarian function
Clotting
Energy expenditure

Question 5

How does insulin drive glucose into muscle?

Answer 5

Via GLUT-4

Question 6

Where is GLUT-4 stored?

Answer 6

In vesicles

Question 7

What does insulin cause for GLUT-4?

Answer 7

GLUT-4 incorporated into the membrane on muscle cells
Hydrophilic core allows glucose transport
Hydrophobic exterior means it can sit in membrane

Question 8

How does glucose uptake change when insulin is released?

Answer 8

Insulin causes a 7-fold increase in glucose uptake

Question 9

How does insulin affect the use of protein in muscle cells?

Answer 9

Increase protein synthesis

Decrease proteolysis

Question 10

Glucose in blood

Answer 10

Present all the time

Not only after meals

Question 11

What is the name of stored glucose in the liver?

Answer 11

Glycogen

Question 12

In the liver, when blood glucose is low, (fasting state) gluconeogenesis occurs

Answer 12

Break down protein

Gluconeogenic AAs can be used to make glucose

Question 13

In the liver, when blood glucose is high and insulin is released

Answer 13

Gluconeogenic AAs can enter liver and be used to make protein

Question 14

Carbohydrate in the form of glycogen in liver and muscle is a

Answer 14

short term energy store

Question 15

Fat has a high energy concentration

Answer 15

Takes a long time to break down

Question 16

Insulins’ effect on adipocytes

Answer 16

In blood, Triglyceride broken down by lipoprotein lipase (encouraged by insulin), so
Glycerol and NEFAs can enter adipocyte.
Glucose can enter via GLUT-4 and can be used to make NEFAs and glycerol-3-P.
Insulin within cell encourages formation off triglyceride

Question 17

Triglyceride can be broken down in fight or flight

Answer 17

To make glycerol and NEFA

Question 18

NEFA

Answer 18

Non-esterified fatty acid

Question 19

How do we store fat?

Answer 19

In adipocytes

Question 20

Omental adipocytes

Answer 20

more metabolically and endocrinology active due to anatomical location (Central)

Question 21

What does more omental fat increase?

Answer 21

Risk of heart disease

Question 22

Glycerol enters liver cells

Answer 22

Phosphorylated to make Triacylglyerol (Triglyceride)
Triglyceride can be used to make glycerol and then glucose
= Gluconeogenesis

Question 23

NEFA in liver cells

Answer 23

Can’t be used to make glucose, only the glycerol bit

Question 24

What can the brain use as energy substrates?

Answer 24

Glucose

Ketone bodies

Question 25

What can't the brain use as an energy substrate?

Answer 25

Fatty acids | Brain fundamentally different from other parts of body

Question 26

Fatty acids can be used to make ketone bodies

Answer 26

Insulin stops this | Glucagon stimulates this

Question 27

How can NEFAs be used to make ketone bodies?

Answer 27

NEFA enter liver NEFA broken into Acetoacetate and 3-Hydroxybutarate Which leave liver as ketone bodies

Question 28

What does the conversion of NEFAs to ketone bodies allow?

Answer 28

Brain function after fasting

Question 29

If someone has ketones present and a high blood glucose

Answer 29

They are insulin deficient | As when there is plenty of glucose, it is unnecessary to make ketone bodies

Question 30

What can glycogen in liver be broken down into?

Answer 30

Glucose by glucagon | = glycogenolysis

Question 31

2 ways of supporting HGO

Answer 31

Glycogenolysis | Gluconeogenesis

Question 32

Why can't muscle release glucose?

Answer 32

Glycogen in muscle is just used by muscle, can't be used to support plasma glucose

Question 33

Fasted state concentrations

Answer 33

Low insulin to glucagon ratio Glucose conc. 3-5.5 mol/l Increase conc. NEFA Decrease conc. AA

Question 34

Fasted state actions

Answer 34

Increase proteolysis, lipolysis, glycogenolysis and gluconeogenesis Increase HGO

Question 35

Fasted state use of energy substrates

Answer 35

Muscle uses lipids Brain uses glucose, later ketones Increased ketogenesis in brain when prolonged fasting

Question 36

Fed state concentrations

Answer 36

Stored insulin released, then 2nd phase High insulin to glucagon ratio Increase conc. glycogen

Question 37

Fed state actions

Answer 37

Increase protein synthesis and lipogenesis | Decrease proteolysis and gluconeogenesis

Question 38

Presentation of T1DM

Answer 38

Absolute insulin deficiency

Question 39

How does weight loss occur in T1DM?

Answer 39

Proteolysis and lipolysis continue

Question 40

T1DM Glucose exceeds kidneys ability to reabsorb glucose

Answer 40

= Glucose and ketones in urine | Glycosuria and ketonuria with osmotic symptoms

Question 41

Insulin induced hypoglycaemia

Answer 41

Increased insulin so Glucose enters muscle Glucagon increases, triumphs over insulin Increase HGO with gluconeogenesis and glycogenolysis Increase in catecholamines, cortisol and growth hormone

Question 42

How to treat insulin induced hypoglycaemia in an emergency

Answer 42

Intravenous/ intramuscular glucagon

Question 43

T2DM insulin resistance resides in

Answer 43

Liver, muscle and adipose tissue | Affects intermediary metabolism, glucose and fatty acids

Question 44

In T2DM insulin resistance, there is usually enough insulin to suppress

Answer 44

Ketogenesis Proteolysis So don't lose weight or produce unnecessary ketones

Question 45

What are the 2 effects insulin has after binding to the insulin receptor?

Answer 45

MAP Kinase pathway | Insulin receptor PI3 Kinase pathway

Question 46

What is the Insulin receptor PI3 Kinase pathway?

Answer 46

Metabolic actions on glucose, fats and AAs

Question 47

What is the MAP kinase pathway?

Answer 47

Causes growth and proliferation

Question 48

Which pathway is affected in T2DM insulin resistance?

Answer 48

Insulin resistance PI3 Kinase pathway

Question 49

Compensatory hyperinsulinemia

Answer 49

Functional pancreas but resistance in the PI3 kinase pathway leads to excessive insulin production to reduce blood sugar Thus increasing MAP kinase pathway - overstimulating growth (mitogenic) pathway

Question 50

What does compensatory hyperinsulinemia cause?

Answer 50

Patient does NOT have T2DM | May have high BP, risk of ischaemic heart disease

Question 51

Hyperinsulinaemic effect of mitogenic effects in insulin resistance

Answer 51

Low HDL cholesterol Smooth muscle hypertrophy Reduced ovarian function Abnormal effects on clotting and energy expenditure

Question 52

Metabolic effect in insulin resistance

Answer 52

``` Insulin resistance effect Fasting glucose >6mmol High [TG] Low [HDL] High BP High waist circumference ```

Question 53

BP is a major issue in T2DM

Answer 53

Causes damage to arteries

Question 54

Presentation of T2DM

Answer 54

``` Insulin resistance Majority obese Dyslipidaemia Later insulin deficiency Hyperglycaemia Less osmotic symptoms With complications ```

Question 55

Dyslipidaemia

Answer 55

Abnormal carriage of lipids in circulation

Question 56

Why is T2DM often presented with complications?

Answer 56

Often not found for years | Subtle

Question 57

Healthy eating for T2DM

Answer 57

Total calorie control Reduce calories from fat and refined carbohydrate Increase soluble fibre and calories from complex carbohydrate Decrease sodium