Insulin (Secretion and Action) Flashcards Preview

METABOLISM 2 > Insulin (Secretion and Action) > Flashcards

Flashcards in Insulin (Secretion and Action) Deck (35):
1

What is an exocrine gland?

A gland that secretes into a duct

2

What is an endocrine gland?

A gland that secretes directly into the bloodstream and surrounding tissues

3

What are incretins?

These are a group of metabolic hormone that stimulate a decrease in blood glucose levels by increasing insulin release from pancreatic beta cells prior to blood glucose level elevation

4

Why is the brain so dependent on extracellular glucose?

It can't synthesis or store glucose or metabolise substrates other than glucose (except for ketones) and it also can't extract enough glucose for the extracellular fluid at lower concentrations

5

What 5 cell types are present in the pancreatic Islet of Langerhans?

Alpha cells, beta cells, delta cells, PP cells and epsilon cells

6

What is the role of alpha cells in the pancreatic Islets of Langerhans?

Produce glucagon

7

What is the role of beta cells in the pancreatic Islets of Langerhans?

Produce insulin

8

What is the role of delta cells in the pancreatic Islets of Langerhans?

Produce somatostatin

9

What is the role of PP cells in the pancreatic Islets of Langerhans?

Produce pancreatic polypeptide

10

What is the role of epsilon cells in the pancreatic Islets of Langerhans?

Produce ghrelin

11

Describe the process of insulin production

Pancreatic beta cells synthesis pre-proinsulin which is then transported to the ER where it is modified and cleaved to form proinsulin. This proninsulin enters the golgi apparatus and is converted to active insulin by endopeptidases (carboxypeptidase E); this cleaves off the C group and the B and A groups connect by a disulphide bond

12

At what four stages can insulin production be regulated?

At the transcription from the insulin gene, mRNA stability, mRNA translation and post-translational modification

13

Outline the process that leads to insulin secretion from pancreatic beta cells

Glucose enters the beta cell via the GLUT2 transporter which stimulates glucokinase (GK) which phoshorylates the glucose to prevent it leaving the cell. The glucose is then used in aerobic respiration where it generates a ATP; the resultant increase ATP:ADP ratio closes the K+ channels which leads to membrane depolarisation which opens the Ca2+ channel which then acts on the vesicles containing insulin and facilitates exocytotic release

14

What type of GLUT receptor is present on pancreatic beta cells?

GLUT2

15

Where is the glucokinase enzyme found?

Only in the liver, hexokinase is found everywhere else

16

What three substances amplify insulin secretion?

Amino acids, incretins and phospholipase C

17

How can amino acids act to amplify insulin secretion?

Increasing the ATP: ADP ratio to shut the K+ channel:
- Increased breakdown of amino acids in cells leads to an increased ATP
- Leucine can activate glutamate dehydrogenase (GDH) which can contribute a molecule to the Kreb's cycle (alpha-ketoglutarate)
- Leucine can be converted by transamination into alpha-ketoisocaproate (KIC) which is converted to acetyl CoA and increases ATP ratio again

Direct depolarisation:
Some amino acids such as arginine can directly depolarise the plasma membrane to cause Ca2+ channel opening

18

How can incretins act to amplify insulin secretion?

After food intake there is GLP-1 (glucagon-like peptide 1) secretion which stimulates insulin secretion by acting on the GLP-1R which stimulates the beta cell, but glucose is required for this activation of insulin secretion

19

How can phospholipase C amplify insulin secretion?

Phospholipase C cleaves PIP2 into IP3 and diacylglycerol (DAG). The IP3 binds to receptors in the endoplasmic reticulum of beta cells which allows Ca2+ release which can stimulate further vesicle release

20

What signals trigger insulin release besides glucose?

• Amino acids arginine and leucine
• GLP-1 (gastrointestinally-derived incretins)
• GIP (glucose-dependent insulinotropic peptide)
• Fatty acids
• Acetylcholine (parasympathetic release via phospholipase C)
• CCK (cholecystokinin via phospholipase C)

21

What are the metabolic actions of insulin on muscle tissue?

Stimulates glycogen synthesis as it activates protein kinase B (Akt) which induces GLUT4 translocation in smooth muscle and phosphorylates/inactivate glycogen synthase kinase leading to activation of glycogen synthesis --> increased glycogenesis

22

What are the major metabolic actions of insulin on adipocytes?

Stimulates glucose uptake, lipogenesis and inhibits lipolysis (via inhibiting lipase)

23

How can incretins act to amplify insulin secretion?

After food intake there is GLP-1 (glucagon-like peptide 1) secretion which stimulates insulin secretion by acting on the GLP-1R which stimulates the beta cell, but glucose is required for this activation of insulin secretion

24

How can phospholipase C amplify insulin secretion?

Phospholipase C cleaves PIP2 into IP3 and diacylglycerol (DAG). The IP3 binds to receptors in the endoplasmic reticulum of beta cells which allows Ca2+ release which can stimulate further vesicle release

25

What signals trigger insulin release besides glucose?

• Amino acids arginine and leucine
• GLP-1 (gastrointestinally-derived incretins)
• GIP (glucose-dependent insulinotropic peptide)
• Fatty acids
• Acetylcholine (parasympathetic release via phospholipase C)
• CCK (cholecystokinin via phospholipase C)

26

What are the metabolic actions of insulin on muscle tissue?

Stimulates glycogen synthesis as it activates protein kinase B (Akt) which induces GLUT4 translocation in smooth muscle and phosphorylates/inactivate glycogen synthase kinase leading to activation of glycogen synthesis --> increased glycogenesis

27

What factors can reduce insulin signalling?

Endocytosis/degradation of the insulin receptor, dephosphorylation of the tyrosine residues on the beta subunit of the IR due to tyrosine phosphatases, decrease in the number of receptors and serine/threonine kinases reduce the activity of insulin by phosphorylating IRS so it can't bind to the tyrosine kinase end of the IR.

28

What are the major metabolic actions of insulin on hepatocytes?

Increases glucose uptake by increasing GK activity, increases glycogenesis, increase lipogenesis (form lipoproteins) and inhibits gluconeogenesis

29

How does insulin affect protein synthesis?

It stimulate amino acid uptake and translation of mRNAs in order to increase protein synthesis, and inhibits protein breakdown; promotes an anabolic state

30

Outline how the insulin receptor is activated

Two molecules of insulin bind to the extracellular alpha subunits which causes a conformational change in the chains. This change activates the kinase domain of the receptor on the intracellular portion of the beta subunits. The activated kinase domain then phosphorylates the tyrosine residues on the C-terminus of the receptor as well as those on the adaptor protein (IRS)

31

Outline the mechanism of intracellular insulin signalling

Insulin binds to the IR and causes the receptor to become phosphorylated which allows IRS to bind. PI3K (lipid kinase) is then recruited which works to phosphorylate PIP2 to PIP3. As a result, protein kinase (Akt) can bind to PIP3 which then allows the phosphorylation of downstream factors which allows translocation of GLUT4 to the surface of muscle and adipocytes

32

What are the consequences of insulin resistance on the liver?

Reduced glycogen synthesis, reduced lipogenesis, increased gluconeogenesis and increased glycogenolysis

33

What are the consequences of insulin resistance on the muscle?

Reduced glucose uptake, reduced glycogen synthesis and increased protein catabolism

34

What are the consequences of insulin resistance on adipocytes?

Reduced glucose uptake, reduced lipogenesis and increased lipolysis

35

How does the metabolism react to short-term fasting?

The liver releases glucose into the bloodstream via glycogenolysis and gluconeogenesis (amino acids and glycerol can be used as precursors)