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Endocrinology > Insulin secretion & intermediary metabolism > Flashcards

Insulin secretion & intermediary metabolism Flashcards

1
Q

What hormones can increase blood glucose concentration?

A

Glucagon
Catecholamines
Somatotrophin
Cortisol

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2
Q

Type 1 Diabetes

A

Elevated blood glucose where insulin is required to prevent ketoacidosis

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3
Q

Simple definition of T1D

A

Inability to create insulin

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4
Q

How many sorts of T1D are there?

A

10

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5
Q

Simple definition Type 2 Diabetes

A

Lack of response to insulin

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6
Q

How many sorts of T2D are there?

A

50

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7
Q

Proportion of diabetes mellitus cases by type

A

86% T2D
11% T1D
3% MODY

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8
Q

MODY

A

Mature onset diabetes of the young

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9
Q

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

A

CNS

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10
Q

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

A

Hypoglycaemia

Brain function increasingly impaired

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11
Q

What happens if blood glucose falls below 2mM?

A

Unconsciousness
Coma
Eventually death

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12
Q

What hormone can decrease blood glucose concentration?

A

Insulin

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13
Q

98% pancreas is associated with

A

Exocrine secretions via duct to small intestine

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14
Q

Remaining 2% of pancreatic tissue

A

Islets of Langerhans

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15
Q

Paracrine

A

One cell affects cell next to it

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16
Q

Cells of the pancreas use

A

Gap junctions to allow paracrine transport effects

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17
Q

Alpha cells secrete

A

Glucagon

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18
Q

Glucagon action

A

Increases blood glucose

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19
Q

Beta cells secrete

A

Insulin

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20
Q

Insulin action

A

Stimulates growth

Decreases blood glucose

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21
Q

Delta cells secrete

A

Somatostatin

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22
Q

Somatostatin action

A

Decreases production of insulin and glucagon

Has “calming down” effect

23
Q

What increases insulin secretion?

A

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

24
Q

Neurological control of beta-cells: Sympathetic stimulation:

A

decreases insulin production

25
Q

Neurological control of beta- cells: Parasympathetic stimulation

A

increases insulin production

26
Q

Name 4 physiological actions of insulin

A

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

27
Q

What increases glucagon secretion?

A

Decreased blood glucose
Certain amino acids
Certain GI hormones

28
Q

Neurological control of alpha-cells:

Sympathetic stimulation

A

Increases glucagon production

29
Q

Neurological control of alpha-cells:

Parasympathetic stimulation

A

Increases glucagon production

30
Q

4 physiological actions of glucagon

A

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

31
Q

How does glucose enter a beta cell?

A

Via Glucose Transporter 2 (GLUT-2)

Not insulin regulated

32
Q

What is the rate determining step in regulating insulin secretion?

A

Conversion of glucose to glucose-6-phosphate

by glucokinase

33
Q

What is glucokinase nicknamed?

A

The “glucose sensor”

Important for sensing glucose concentration by beta cell

34
Q

What is the precursor of insulin?

A

Pre-proinsulin

35
Q

Describe pre-proinsulin

A

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

36
Q

What is the final sequence in pre-proinsulin?

A

C Peptide

37
Q

When is C-Peptide removed?

A

Upon release outside the cell

38
Q

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

A

1:1

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

39
Q

Why would it be easier to measure C peptide than insulin

A

C peptide has a longer half life

40
Q

Why can’t insulin enter cells?

A

Insulin is a large protein so has to act on receptors

41
Q

Mechanism for insulin secretion

A
  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.
42
Q

Incretin Effect

A

Glucose stimulates more insulin secretion when given orally rather than intravenously

43
Q

Glucagon like peptide 1 (GLP-1)

A

Gut hormone, secreted in response to nutrients in gut

44
Q

What is GLP-1 a transcription product of?

A

Proglucagon gene, mostly from L cell

45
Q

GLP-1 actions

A

Stimulates insulin

Suppresses glucagon

46
Q

What feeling does GLP-1 increase?

A

Satiety (fullness)

47
Q

What is the half life of GLP-1

A

Short

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

48
Q

1st phase insulin response

A

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

49
Q

Why is 1st phase insulin needed?

A

To switch off liver glucose production

50
Q

Do those with T2D have a 1st phase response?

A

No

Insulin made slower/ later

51
Q

How does insulin effect cells?

A

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

52
Q

Which subunits of the insulin receptor span the membrane?

A

Beta subunits

53
Q

Insulin resistance in T2D area of error

A

Post-receptor cytoplasmic effects of insulin

Endocrinology (12 decks)

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