Insulin secretion & intermediary metabolism

Question 1

What hormones can increase blood glucose concentration?

Answer 1

Glucagon
Catecholamines
Somatotrophin
Cortisol

Question 2

Type 1 Diabetes

Answer 2

Elevated blood glucose where insulin is required to prevent ketoacidosis

Question 3

Simple definition of T1D

Answer 3

Inability to create insulin

Question 4

How many sorts of T1D are there?

Answer 4

10

Question 5

Simple definition Type 2 Diabetes

Answer 5

Lack of response to insulin

Question 6

How many sorts of T2D are there?

Answer 6

50

Question 7

Proportion of diabetes mellitus cases by type

Answer 7

86% T2D
11% T1D
3% MODY

Question 8

MODY

Answer 8

Mature onset diabetes of the young

Question 9

What completely relies on glucose as an energy substrate in normal conditions?

Answer 9

CNS

Question 10

What happens if blood glucose falls below 4/5 mM?

Answer 10

Hypoglycaemia

Brain function increasingly impaired

Question 11

What happens if blood glucose falls below 2mM?

Answer 11

Unconsciousness
Coma
Eventually death

Question 12

What hormone can decrease blood glucose concentration?

Answer 12

Insulin

Question 13

98% pancreas is associated with

Answer 13

Exocrine secretions via duct to small intestine

Question 14

Remaining 2% of pancreatic tissue

Answer 14

Islets of Langerhans

Question 15

Paracrine

Answer 15

One cell affects cell next to it

Question 16

Cells of the pancreas use

Answer 16

Gap junctions to allow paracrine transport effects

Question 17

Alpha cells secrete

Answer 17

Glucagon

Question 18

Glucagon action

Answer 18

Increases blood glucose

Question 19

Beta cells secrete

Answer 19

Insulin

Question 20

Insulin action

Answer 20

Stimulates growth

Decreases blood glucose

Question 21

Delta cells secrete

Answer 21

Somatostatin

Question 22

Somatostatin action

Answer 22

Decreases production of insulin and glucagon

Has “calming down” effect

Question 23

What increases insulin secretion?

Answer 23

Increased blood glucose
Some GI tract hormones
Glucagon like peptide (GLP)

Question 24

Neurological control of beta-cells: Sympathetic stimulation:

Answer 24

decreases insulin production

Question 25

Neurological control of beta- cells: Parasympathetic stimulation

Answer 25

increases insulin production

Question 26

Name 4 physiological actions of insulin

Answer 26

Increases glycolysis Increases glucose transport into cells via GLUT-4 Increases glycogenesis and lipogenesis Decreases break down of proteins and lipids

Question 27

What increases glucagon secretion?

Answer 27

Decreased blood glucose Certain amino acids Certain GI hormones

Question 28

Neurological control of alpha-cells: | Sympathetic stimulation

Answer 28

Increases glucagon production

Question 29

Neurological control of alpha-cells: | Parasympathetic stimulation

Answer 29

Increases glucagon production

Question 30

4 physiological actions of glucagon

Answer 30

Main effects are on the liver- increases HGO Increased hepatic glycogenolysis Increased amino acid transport into liver- Increased gluconeogenesis Increased lipolysis- Increased gluconeogenesis

Question 31

How does glucose enter a beta cell?

Answer 31

Via Glucose Transporter 2 (GLUT-2) | Not insulin regulated

Question 32

What is the rate determining step in regulating insulin secretion?

Answer 32

Conversion of glucose to glucose-6-phosphate | by glucokinase

Question 33

What is glucokinase nicknamed?

Answer 33

The "glucose sensor" | Important for sensing glucose concentration by beta cell

Question 34

What is the precursor of insulin?

Answer 34

Pre-proinsulin

Question 35

Describe pre-proinsulin

Answer 35

3 chains joined to form 1 long chain with a signal sequence

Question 36

What is the final sequence in pre-proinsulin?

Answer 36

C Peptide

Question 37

When is C-Peptide removed?

Answer 37

Upon release outside the cell

Question 38

What is the molar ratio of insulin to C-peptide?

Answer 38

1:1 | By measuring C peptide we can see if the beta cells are functioning

Question 39

Why would it be easier to measure C peptide than insulin

Answer 39

C peptide has a longer half life

Question 40

Why can't insulin enter cells?

Answer 40

Insulin is a large protein so has to act on receptors

Question 41

Mechanism for insulin secretion

Answer 41

1. Glucose enters through GLUT-2 and is used for ATP generation using glucokinase. 2. ATP blocks the ATP-sensitive K+ channels. 3. This triggers opening of voltage gated Calcium ion channels 4. Calcium rushes into the beta-cell & insulin is secreted via regulated secretion.

Question 42

Incretin Effect

Answer 42

Glucose stimulates more insulin secretion when given orally rather than intravenously

Question 43

Glucagon like peptide 1 (GLP-1)

Answer 43

Gut hormone, secreted in response to nutrients in gut

Question 44

What is GLP-1 a transcription product of?

Answer 44

Proglucagon gene, mostly from L cell

Question 45

GLP-1 actions

Answer 45

Stimulates insulin | Suppresses glucagon

Question 46

What feeling does GLP-1 increase?

Answer 46

Satiety (fullness)

Question 47

What is the half life of GLP-1

Answer 47

Short | Due to rapid degradation from enzyme: Dipeptidyl peptidase-4 (DPPG-4 inhibitor)

Question 48

1st phase insulin response

Answer 48

Healthy person has IV glucose load that makes them produces insulin instantly

Question 49

Why is 1st phase insulin needed?

Answer 49

To switch off liver glucose production

Question 50

Do those with T2D have a 1st phase response?

Answer 50

No | Insulin made slower/ later

Question 51

How does insulin effect cells?

Answer 51

Insulin bonds to alpha subunits of receptor causing a conformational change in beta subunits Phosphorylation of beta subunits recruits substrates which have an effect on metabolic pathway Glucose synthesis ceases

Question 52

Which subunits of the insulin receptor span the membrane?

Answer 52

Beta subunits

Question 53

Insulin resistance in T2D area of error

Answer 53

Post-receptor cytoplasmic effects of insulin