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LR Endocrine > Endocrine Pancreas > Flashcards

Endocrine Pancreas Flashcards

1
Q

Type 1 diabetes occurs due to…

A

Autoimmune destruction of beta cells

This leads to insulin deficiency

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2
Q

Type 2 diabetes occurs due to…

A

Insulin resistance + beta cell dysfunction

This leads to relative insulin deficiency

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3
Q

The endocrine cells of the pancreas are found in clusters known as…

A

The Islets of Langerhans

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4
Q

What % of pancreatic volume is made up of the islets of langerhans?

A

1-2%

The rest is exocrine acinar cells which secrete digestive juices

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5
Q

List 5 different islet cell types and what they secrete

A

Alpha cells -> glucagon

Beta cells -> insulin

Delta cells -> somatostatin

PP cells -> pancreatic polypeptide

Epsilon cells -> ghrelin

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6
Q

Roughly what proportion of the pancreatic islets are alpha, beta, delta and PP cells?

A

Beta - 55%
Alpha - 38%
Delta - <5%
PP - ~1%

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7
Q

At what blood glucose threshold is insulin released?

A

When BG >5.5 mmol/L

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8
Q

At what blood glucose threshold is glucagon released?

A

When BG <4 mmol/L

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9
Q

Describe regulation of glucose homeostasis by insulin

A
  • Hyperglycaemia and hyperlipidaemia occur during feeding
  • Pancreatic beta cells release insulin when glucose >5.5 mmol/L
  • Glycogen synthesis and lipid storage occur due to uptake of glucose into the liver, muscle and fat
  • Blood glucose and lipid levels drop back to normal
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10
Q

Beta cells are switched off at low glucose levels. T/F

A

True

And alpha cells are switched off at high glucose levels

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11
Q

Describe regulation of glucose homeostasis by glucagon

A
  • Hypoglycaemia and hypolipidaemia occur during fasting/exercise
  • Pancreatic alpha cells release glucagon when glucose <4 mmol/L
  • Glycogen breakdown and lipolysis occur
  • Blood glucose and lipid levels raise back to normal
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12
Q

In T2DM, beta cell mass in the pancreas decreases, suggesting that…

A

Beta cells are lost or dedifferentiate

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13
Q

When insulin resistance first develops, why does T2DM not immediately occur?

When does T2DM occur?

A

Beta cells release more insulin to compensate

T2DM occurs when beta cells fail to produce enough insulin to meet demands

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14
Q

Describe how glucose binds to beta cells and causes insulin release

A
  • Glucose taken in by GLUT 2 transporters
  • Glucokinase converts it to glucose-6-phosphate which is used in glycolysis, the TCA cycle and oxidative phosphorylation to produce ATP
  • ATP binds to ATP sensitive K+ channels, causing them to close
  • K+ builds up in the cell, depolarising the membrane
  • Ca2+ can enter through voltage gated Ca2+ channels
  • Ca2+ triggers insulin granule exocytosis
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15
Q

Insulin secretion often loses its biphasic nature in type 1 diabetes. T/F

A

False

Insulin secretion often loses its biphasic nature in type 2 diabetes

Insulin is not secreted in type 1 diabetes

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16
Q

Besides glucose, what other molecules do beta cells regulate insulin in response to?

A

Nutrients e.g., free fatty acids, amino acids

Hormones e.g., leptin, adiponectin, IGF1, glucagon

Neurotransmitters e.g., acetylcholine

17
Q

Describe how hypoglycaemia causes glucagon release from alpha cells

A
  • Glucose uptake and metabolism is low so KATP channels open
  • K+ leaves the cell
  • Voltage gated Na+ channels (NaV) open, allowing Na+ to enter the cell
  • This triggers action potentials that open P/Q type voltage gated Ca2+ channels (CaV)
  • Ca2+ entry triggers glucagon granule exocytosis
18
Q

Where does glucagon have its biggest effect once it is released? What does it do here?

A

In the liver

Glucagon stimulates hepatic glucose output by promoting glycogen breakdown

It also stimulates gluconeogenesis

19
Q

What alpha cell defect may be seen contributing to hyperglycaemia in T2DM?

A

Glucagon may still be released in the fed state which means that hepatic glucose production is still being stimulated

This contributes to hyperglycaemia

20
Q

Define an exocrine cell in relation to the pancreas

A

A cell which secretes digestive juices into the ducts which drain into the gut

21
Q

Define an endocrine cell in relation to the pancreas

A

A cell which secretes hormones into the blood stream which then travel to distal target organs

22
Q

Define a paracrine cell

A

A cell which releases a soluble factor which then influences adjacent cells

23
Q

Define an autocrine cell

A

A cell which releases a soluble factor which binds to a receptor on that same cell

24
Q

Define a juxtacrine cell

A

A cell which presents a ligand on its surface which will interact with the cell next to it

25
Q

Describe the paracrine action of delta cells

A

Delta cells secrete somatostatin 14 which suppresses beta and alpha cell function in a paracrine manner

26
Q

Delta cells release SST14 in response to…

A

Nutrients, hormones and neurotransmitter stimulation

27
Q

How does somatostatin 14 suppress alpha and beta cells?

A

It binds to G-protein coupled receptors which are coupled to Gi (inhibitory) proteins

This inhibits cAMP production

28
Q

Why are delta cells good at suppressing multiple alpha and beta cells at a time?

A

They have an unusual neuron-like shape that allows them to be in contact with multiple cells

29
Q

What is meant by the incretin effect?

A

Insulin secretion is greater in response to oral glucose in comparison with IV glucose infusion

30
Q

What are incretins?

A

Hormones released from the gut which stimulate insulin release in response to oral glucose (i.e., glucose dependent)

31
Q

What is the main incretin hormone?

A

Glucagon-like peptide 1 (GLP1)

32
Q

GLP1 incretin hormone is released from ? cells in the small and large intestines

A

L-cells

33
Q

Which enzyme is responsible for the breakdown of incretins?

A

DPP4

34
Q

When might a DPP4 inhibitor be used?

A

To increase release of insulin for treatment of hyperglycaemia in T2DM
(as less incretins are being broken down so more are available to stimulate insulin release)

LR Endocrine (12 decks)

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