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BRS Endocrinology > Glucose Homeostasis > Flashcards

Glucose Homeostasis Flashcards

1
Q

Why is glucose important?

A

Glucose is an important energy substrate

Especially for the CNS

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2
Q

Why is glucose so important for the CNS?

A

If the blood glucose concentration falls much below normal levels of 4-5 mmol/L (hypoglycaemia), then cerebral function is increasingly impaired.

If blood glucose concentration <2 mmol/L, unconsciousness, coma and ultimately death can result.

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3
Q

How is glucose regulated?

A

Glucose is closely regulated
Feedback system is needed for this regulation
Persistent hyperglycemia results in diabetes mellitus

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4
Q

What increases blood glucose?

A

Glucagon
Cortisol
GH
Catecholamines

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5
Q

What decreases blood glucose?

A

Insulin

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6
Q

What % of people are affected with diabetes mellitus in the UK?

A

7%

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7
Q

What is the % risk increase risk of a person with diabetes mellitus dying relative to an age-matched control without diabetes mellitus?

A

34%

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8
Q

How much of the NHS budget is spent on diabetes mellitus?

A

10%

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9
Q

What is the most prevalent form of diabetes?

A

Type 2 diabetes mellitus

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10
Q

What are the types of diabetes?

A

Maturity onset diabetes of the young (MODY)
T1/2DM

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11
Q

what type of structure is the pancreas?

A

Retroperitoneal structure

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12
Q

What does retroperitoneal structure mean?

A

Having to do with the area outside or behind the peritoneum

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13
Q

What is the peritoneum?

A

a membrane, a sheet of smooth tissue that lines your abdominopelvic cavity and surrounds your abdominal organs

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14
Q

What does most of the pancreas generate?

A

98% generates exocrine secretions via duct to small intestine

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15
Q

What is the rest of the 2% of the pancreas?

A

Small clumps of cells within pancreatic tissue (remaining 2%) are called islets of Langerhans

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16
Q

How much of the pancreatic blood flow goes to the islets of langerhans?

A

10-15%

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17
Q

What are the cells in the islets of langerhans and what do they secrete?

A

alpha cells= glucagon

beta cells= insulin

gamma cells= somatostatin

18
Q

What are the junctions between the cells in the islets of langerhans?

A

Tight junctions and gap junctions

19
Q

What type of communication between islet cells?

A

Paracrine

20
Q

What are gap junctions?

A

Allow small molecules to pass directly between cells

21
Q

What are tight junctions?

A

Create small intercellular spaces

22
Q

How much of the islets are each type of cell?

A

alpha= 30%
beta= 60%
gamma= 10%

*they are all involved in glucose homeostasis

23
Q

What are the actions of pancreatic hormones?

A

Somatostatin inhibits both insulin and glucagon

Insulin decreases blood glucose
Glucagon increases blood glucose

Insulin promotes growth and development

24
Q

What increases and decreases insulin secretion from B cells when there is an increase in blood glucose?

A

Increases:
some AA
some GI hormones
glucagon from a cells
Parasympathetic activity
Sympathetic activity via Beta (much lesser extent)

Decreases:
Somatostatin
Sympathetic nervous system activity via alpha

25
Q

What does insulin cause in liver (7)

A

Build-up of glycogen stores (glycogenesis)
breakdown of glucose (glycolysis)
Increased uptake of glucose

Additional actions of insulin are:
Increase of protein synthesis
Reduction in breakdown of fat

increase glucose transport into cells via GLUT4

increase amino acid transport and protein synthesis

decreased lipolysis and increased lipogenesis

26
Q

what promotes and inhibits alpha cells when blood glucoses decreases?

A

Increase:
some AA
some GI hormones
SNS activity via alpha
PNS activity (para)

decrease:
somatostatin
insulin

Physiological changes occur in response to reductions in glucose values
These are required to ensure glucose levels do not continue to fall thereby compromising energy/ substrate delivery

27
Q

How does the liver react to increased glucagon from reduced blood glucose? (4)

A

Increase AA transport in liver
Increase gluconeogenesis
Increase hepatic glycogenolysis
Increase lipolysis

AA and fatty acid increase=> gluconeogenesis

28
Q

Is GLUT2 sensitive to insulin?

A

No

29
Q

What is the role of glucokinase?

A

promote glucose-> glucose-6-phosphate

glucokinase= hexokinase IV

30
Q

what causes cells to secrete insulin?

A
  1. glucose enters the cell via GLUT2
  2. Glucose is converted to glucose-6-phosphate (rate-limiting step) via glucokinase
  3. Glucose-6-P forms ATP
  4. this ATP binds to a potassium ion channel and closes it
  5. intracellular K+ causes calcium ion channels to open allowing Ca2+ to enter the cell
  6. intracellular shift of calcium leads to release of stored insulin

*none of this process is restricted

31
Q

How is C-peptide related to insulin?

A

Proinsulin is made of c peptide and insulin

Via proteolytic cleavage

32
Q

What is insulin composed of?

A

A chain and B chain with disulphide bridges between them

33
Q

What does measuring C peptide help show?

A

How much insulin your body is making

34
Q

What are incretins?

A

Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating.

35
Q

What is evidence of a gastrointestinal incretin effect?

A

food sitting in stomach enhances insulin

36
Q

What is Glucagon like peptide-1 (GLP-1)?

A

Gut hormone
- Secreted in response to nutrients in gut
- Transcription product of pro-glucagon gene, mostly from L-cell

37
Q

What does glucagon like peptide-1 (GLP-1) stimulate and suppress?

A

Stimulates insulin and suppresses glucagon

38
Q

What does glucagon like peptide-1 (GLP-1) do?

A

↑ satiety (feeling of ‘fullness’)

39
Q

What is the half life of glucagon like peptide-1 (GLP-1)?

A

Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)

40
Q

What is glucagon like peptide-1 (GLP-1) used to treat?

A

diabetes and obesity

41
Q

What happens during the First phase insulin release (FPIR) during the IV glucose challenge between normal glucose tolerance and type 2 diabetes mellitus?

A
42
Q

Describe the insulin receptor?

A

Insulin binds to the extracellular domain of the insulin receptor

Once insulin binds to the a-subunit, there is a conformational change in the tyrosine kinase domains of the b-subunits

BRS Endocrinology (12 decks)

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