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GI and metabolism > Acute regulation of glucose > Flashcards

Acute regulation of glucose Flashcards

1
Q

Within what range must plasma [glucose] remain?

A

3-10 mM

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2
Q

Which of the glucose transporters (SGLT or GLUT) require Na+?

A

SGLT

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3
Q

Which of the GLUT transporters is insulin responsive?

A

GLUT-4

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4
Q

What are the most abundant cells in the islets of Langerhans, what do they secrete and where are they located?

A

Beta cells - centrally located. Insulin.

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5
Q

Where are alpha cells found and what do they secrete?

A

At the periphery - secreting glucagon.

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6
Q

What do delta cells secrete?

A

Somatostatin

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7
Q

What do F cells secrete?

A

Pancreatic polypeptide.

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8
Q

How do beta cells sense glucose (and AA)?

A

By using it to make ATP.

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9
Q

Which transporter does glucose use to enter beta cells?

A

GLUT-2 - insulin insensitive and low affinity

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10
Q

What is the effect of a rising [ATP] within the beta cell?

A

Closes K+ATP channel depolarising the membrane. Ca2+ influx and CICR induce exocytosis of insulin.

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11
Q

Do you get a larger insulin response to oral or IV glucose?

A

Oral

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12
Q

What sort of insulin response is elicited by IV glucose?

A

Biphasic

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13
Q

What other pathways may increase insulin exocytosis?

A

Other secretagogues (incretins) act via cAMP or PLC pathways.

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14
Q

Which G protein pathway antagonises the pathway?

A

Gi

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15
Q

What is the effect of the parasympathetic nervous system on secretion?

A

Increases

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16
Q

What is the effect of the sympathetic nervous system on insulin secretion?

A

Inhibits.

17
Q

How is insulin produced?

A

Prohormone

18
Q

How is insulin processed in the Golgi?

A

Cleaved to give A and B chains which are linked by disulphide bridges. Inactive C-peptide also produced.

19
Q

How is C-peptide useful?

A

As a marker of endogenous insulin production.

20
Q

What kind of receptor is the insulin receptor?

A

Tyrosine kinase - TK domains phosphorylate each other and nearby proteins - insulin receptor substrates.

21
Q

What are the two main pathways of insulin receptor signalling?

A

PI3K and PKB phophorylate proteins altering activity and inserting (GLUT 4)

MAPK pathway alters gene expression.

22
Q

What are the effects of insulin on the liver?

A

Glycogen storage and VLDL production increase while gluconeogenesis and ketone body production are inhibited. No GLUT-4 involved.

23
Q

What are the effects of insulin on the muscles?

A

GLUT-4 inserted and favours the use of glucose. Glycogen, triglyceride and protein synthesis increase.

Exercise via adrenaline also induces GLUT-4 and synergises with insulin.

LPL exported to endothelium where it extracts free fatty acids (FFA) from VLDL.

24
Q

What are the effects of insulin on fat?

A

GLUT-4 inserted and favours uptake of glucose. Trigylceride storage increased. Export of FFA and glycerol reduced.

25
Q

What drives the release of glucagon from alpha cells?

A

Amino acids.

26
Q

What antagonises the release of glucagon from alpha cells?

A

Glucose

27
Q

What happens to glucagon in L cells?

A

Converted to GLP1 - potent incretin.

28
Q

What are the effects of glucagon on the liver?

A

Glucagon receptor linked to Gs. Glycogen breakdown and gluconeogenesis increase. Presence of G6Pase allows glucose export. Fatty acids used as an energy source and for ketone body production.

29
Q

What are the effects of glucagon on fat and muscle?

A

At high levels causes: lipolysis in adipocytes, proteolysis (releasing AA for gluconeogenesis) in muscle.

30
Q

What organ clears glucagon?

A

Liver

31
Q

Aside from the pancreas, from where else is somatostatin released?

A

D cells of stomach, duodenum and pancreas. Release stimulated by lumenal H+ and inhibited by ACh.

32
Q

What is the function of somatostatin?

A

Acts on G cells to inhibit the release of gastrin. Also inhibits the release of CCK and secretin (and insulin/glucagon if it can get to the cells).

33
Q

What is the effect of exercise on glucose homeostasis?

A

Adrenaline signals via cAMP to enhance:

  1. Glucose production in the liver (inc. Cori cycle)
  2. Glycogen breakdown in muscle and GLUT4 insertion
  3. Fatty acid release from adipocytes
34
Q

What is the impact of excess glucagon in the type 1 diabetes?

A

Leads to lipolysis an proteolysis.

Gluconeogenesis and ketogenesis in the liver.

35
Q

What are plasma insulin levels in type 2 diabetes?

A

Often high

GI and metabolism (25 decks)

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