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Endocrinology > Insulin secretion and intermediary metabolism > Flashcards

Insulin secretion and intermediary metabolism Flashcards

1
Q

What does diabetes mellitus effect

A

Both lifestyle and lifespan

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2
Q

What is diabetes mellitus the most common cause of

A

Eyesight loss and renal replacement therapy

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3
Q

What is the most important function of the pancreas

A

It’s glucostat function. That is, determining the right amount of insulin to secrete into the bloodstream based on blood glucose levels.

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4
Q

What are patients most worries about when it comes to administering insulin

A

Hypoglycaemia if too much insulin is injected. Patients are worried about this as they can be unsure of how much insulin that they should inject

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5
Q

What molecules can result in an increase in blood glucose concentration

A

GLUCAGON
CATECHOLAMINES
SOMATOTROPHIN
CORTISOL

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6
Q

Which hormone results in a decrease in blood glucose concentration

A

Insulin

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7
Q

What is the importance of this counter-regulation

A

Without it, we would not be able to survive, as we would not be able to maintain blood glucose levels within the normal and optimal range to function

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8
Q

What is T1DM defined as

A

T1DM is defined as elevated glucose where insulin is required to prevent ketoacidosis

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9
Q

What is T2DM defined as

A

T2DM is more common and is a considerable health burden. It is defined in terms of glucose but is also related to hypertension and dyslipidaemia
It is a disease of intermediary metabolism

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10
Q

List the three types of diabetes in order of their prevalence

A

T2DM, MOD, NIDDM
T1DM, IDDM, DY
MODY

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11
Q

Describe MODY

A

Patients do not need insulin to prevent ketoacidosis.
Developed when young- like type 1.
Allowed us to understand the pathophysiology of type 2.

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12
Q

Is the elevation of blood glucose responsible for the damage caused in diabetes mellitus

A

Not necessarily

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13
Q

Can TIDM and T2DM be caused by different underlying mechanisms

A

Yes

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14
Q

What is the role of medicine in DM

A

We treat to help symptoms, complications (morbidity) and mortality

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15
Q

What does modern medicine struggle to do in terms of treating DM

A

Medicine struggles to prevent the long-term complications.

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16
Q

What is meant by diet

A

Altering nutrition. It is something all humans should think about. Total calories and the type of calories that you consume

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17
Q

What is important in treating and preventing DM

A

Diet

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18
Q

When does hypoglycaemia occur

A

Hypoglycaemia occurs when there is imbalance between diet, exercise and insulin

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19
Q

Why can’t insulin be given as a tablet

A

it is digested by gastric acid in the stomach

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20
Q

What is capillary glucose monitoring

A

Needle used to measure glucose in a blood capillary. People complain about this as it is painful. However the homeostatic loop is not complete, we need to match this with the required quantity of insulin

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21
Q

Describe the role of insulin pumps

A

Insulin pumps- give insulin 24 hours a day. However they don’t solve diabetes on their own as we still need to measure blood glucose to decide the quantity of blood glucose to give.

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22
Q

If you are pregnant, how many times should you inject insulin a day

A

7

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23
Q

What does the severity of hypoglycaemia depend on

A

It depends on the individual and their ability to utilise other respiratory substrates.

24
Q

Why is glucose important

A

Glucose is a very important energy substrate, particularly for the CNS which relies on it almost entirely under normal conditions.
If the blood glucose concentration falls much below normal levels of 4-5 mM (hypoglycaemia), then brain function is increasingly impaired.
Below a blood glucose concentration of 2mM unconsciousness, coma and ultimately death can result
Hormones released by stressors stimulate an increase in blood glucose concentration in order to provide this essential substrate to all tissues in times of an emergency (fight or flight response).

25
Q

Describe the two regions of cells found in the pancreas

A

Most of pancreas (98%) is associated
with exocrine secretions via duct to small
intestine
Small clumps of cells within pancreatic
tissue (remaining 2%) are called islets of Langerhans- role in endocrine function of pancreas

26
Q

Describe the anatomical location of the pancreas

A

The pancreas is found in the abdomen and is closely associated with the small intestine.

27
Q

Describe the innervation of the pancreas

A

The innervation is autonomic, with sympathetic and parasympathetic supplies.

28
Q

What is the most common cell type found in the islets of Langerhans

A

Beta cells

29
Q

How are many beta cells linked to their neighbours

A

By gap junctions in the abutting cell membranes, allowing for cross-talk between them by means of small molecules moving between the cells for instance. Furthermore, there are also dynamic tight junctions which can link nearby cells to each other.

30
Q

What are the basic roles of the gap junctions and tight junctions

A 
Gap junctions allow small
 molecules to pass directly
 between cells
Tight junctions form small
 intercellular spaces- they also prevent the loss of hormones
31
Q

How can tight junctions also have a bearing on intercellular communication

A

Tight junctions trap small volumes of ECF between the cells.
If one cell type is stimulated and releases a small quantity of hormone into the general circulation, that same small quantity released into the trapped volume of extracellular fluid could reach much higher concentrations which might effect those nearby cells. These are examples of the different paracrine activity between cells

32
Q

Which hormone do delta cells produce

A

Somatostatin

33
Q

What effect does somatostatin have on insulin and glucagon release

A

It inhibits both the release of glucagon and insulin- it is described as an all purpose negative hormone

34
Q

What is the other metabolic action of insulin

A

It stimulates growth and development

35
Q

Describe the different stimuli for beta cells to secrete insulin

A

Increased blood glucose- stimulatory
Somatostatin- inhibitory
Certain amino acids- stimulatory
Alpha receptors (sympathetic activity)- inhibitory
Beta receptors (parasympathetic activity)- stimulatory
Certain gastrointestinal hormones- Stimulatory
Glucagon- stimulatory

36
Q

Why is it important that sympathetic activity decreases insulin secretion

A

It keeps glucose in blood for use in emergency situations (fight or flight)

37
Q

What are the consequences of having G.I hormones that stimulate insulin release

A

Insulin is released as we eat.

38
Q

What does having mixed meals mean

A

As foods often contain amino acids and glucose- insulin secretion is amplified.

39
Q

Describe the metabolic action of insulin that result in a decrease in blood glucose concentration

A 
Decreased lipolysis
Increased lipogenesis
Increased amino acid 
transport and increased
protein synthesis
Increased glycogenesis
Increased glycolysis
Increased glucose transport into cells via GLUT4
40
Q

Describe the different stimuli for alpha cells to secrete glucagon

A

Decreased blood glucose concentration- stimulatory
Certain amino acids- stimulatory
G.I hormones- stimulatory
Insulin- inhibitory
Somatostatin- inhibitory
Sympathetic and parasympathetic activity- both stimulatory

41
Q

What are the metabolic actions of glucagon that act to increase blood glucose concentration

A

Increased amino acid
transport into liver– increased gluconeogenesis
Increased lipolysis– increased gluconeogenesis
Increased hepatic glycogenolysis

42
Q

What is the basic function of glucokinase (hexokinase IV)

A

It is the glucose sensor

43
Q

Why is it important that beta cells have GLUT-2 receptor and not GLUT-4

A

Beta cell also has a role in glucose sensing through glucokinase. Thus we need glucose to enter through GLUT-2, as insulin increases glucose transport into cells via GLUT-4 , and hence would distort the true glucose readings

44
Q

Describe how glucokinase leads to the release of insulin

A

Glucose —- G6P (Glucokinase) Rate determining step

G6P — Other metabolic pathways — insulin secretion and release

45
Q

Why is it important that glucokinase has rate limitations

A

Only appropriate amount of insulin is produced.

46
Q

Describe the importance of the C-peptide

A

C-peptide is produced in equimolar amounts to insulin, but has a much longer half life. This allows it to be measured more easily than insulin to determine the activity of the pancreas and the levels of insulin in the blood.

47
Q

What steps lead to the release of insulin

A

Glucose enters beta cell via GLUT-2.
Glucose— G6P (glucokinase)
Glycolysis to generate pyruvate- 2ATP.
Insulin synthesis- packaged and stored in secretory granules.
More ATP produced when pyruvate enters Krebs cycle
Stimulation of cell
ATP binds to and closes K+ channels in membrane.
Build up of K+
Depolarisation of cell membrane
VGCCs open
Ca2+ influx
Movement of vesicles towards membrane
Release of insulin into bloodstream by exocytosis.

48
Q

Is insulin released all the time

A

Yes, there is a continual basal release of insulin, with a stimulus-directed release of insulin superimposed upon it. When the beta cells are stimulated, there is a biphasic pattern release of insulin- primary and secondary.

49
Q

How was the gastrointestinal ‘incretin effect’ proved

A

For same quantity of glucose consumed as given intravenously. More insulin was released in response to the ingested glucose. This difference is ascribed to the activity of incretins, secretion of which is increased in response to the presence of food in the gastrointestinal tract.
The incretin effect thus refers to the difference in the magnitude of insulin secretion seen after glucose is ingested, compared with that seen after an isoglycemic IV infusiom

50
Q

Describe glucagon-like-peptide 1

A

Gut hormone
Secreted in response to nutrients in gut
Transcription product of proglucagon gene, mostly from L cell.
Stimulates insulin, suppresses glucagon
Increases satiety
Short half life due to rapid degredation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)- drugs can increase half-life

Has to be injected

Only one needed- not x4 of insulin

Can control weight even when pancreas is damaged- T2DM

51
Q

Describe the two phases of insulin release in healthy patients

A

Initial sharp release of insulin over period of 10 minutes. It is likely that this phase is due to the release of pre-synthesised, rapidly available insulin stored in granules close to the membrane.
A second release is followed, which plateaus around 2-3 hours later
Movement of granules to cell membrane followed by release of insulin, together with the synthesis of new insulin

52
Q

What is different in pre-diabetes and DM

A

No stored insulin to cope with meal- lack of FPIR.

53
Q

Describe the insulin receptor

A 
Belongs to the tyrosine kinase family. 
Extracellular domain (alpha subunit) to which the ligand binds.
Transmembrane domain (beta subunits)
Intracellular domain- which includes the tyrosine kinase catalytic site.
54
Q

What causes the activation of the tyrosine kinase

A

Auto- and cross- phosphorylation of tyrosines in the intracellular domain.

55
Q

Does the insulin receptors function in T2DM

A

Yes, except in rare cases

Endocrinology (11 decks)

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