Acute regulation of glucose Flashcards

1
Q

after a meal what level can portal glucose increase to

A

20 mM

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2
Q

what types of cells secrete glucagon and insulin

A

insulin B cells in the islets of lengerhams

glucagon alpha cells

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3
Q

describe the structure of islets of langerhams between b and a cells

A

b cells mainly central and most abundant

a cells at the periphery

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4
Q

what are the third type of cells in the islet of langerham

A

delta which produce somatostatin and a few f cells which produce pancreatic polypeptide

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5
Q

how do b cells produce insulin

A

sense glucose and aa in the blood by using it to make ATP
entry of glucose via glut2 is insulin sensitive and low affinity
atp closes Katp channels depolarising the membrane
Ca influx and CICR induce exocytosis of insulin

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6
Q

which method of ingesting glucose causes biggest change in insulin

A

oral rather than iv produces more insulin

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7
Q

describe how the nervous system affects insulin production

A

PNS drives and SNS inhibits secretion

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8
Q

how do incretins affect insulin

A

act via cAMP to increases exocytosis

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9
Q

describe the packaging and release of insulin

A

preprohormone from cells and cleaved to pro hormone
internal disulphide bonds fold up
cleaved in golgi to make A and B chains which are linked
C chain used as biomarker

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10
Q

describe the insulin receptor structure

A

a receptor tyrosine kinase - the receptor itself is an enzyme
the TK domains phosphorylate each other and nearby proteins in particular a family of insulin receptor substrates

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11
Q

what are the two main pathways of insulin receptor signalling and what are they both mediated by

A

PI3K and PKB pohorylate proteins altering activity (and inserting GLUT4)

MAPK pathway alters gene expression

both mediated by insulin receptor substrates

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12
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
there is no GLUT4 in the liver

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13
Q

what are the effects of insulin on the muscle

A

GLUT4 inserted and favours use of glucose

glycogen, triglyceride and protein synthesis increase

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14
Q

how does exercise affect insulin on the muscles

A

via adrenaline also induces GLLUT4 and synergises with insulin

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15
Q

what are the effects of insulin on fat

A

GLUT 4 inserted and favours uptake of glucose
Triglyceride storage increased
export of FFA and glycerol is reduced
LPL exported to endothelium where is extracts FFA from VLDL

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16
Q

what is glucagon release driven by inhibited by

A

amino acids and antagonised by glucose

17
Q

what are the effects of glucagon on the liver

A

glucagon is a GPCR receptor and linked to Gs
glycogen breakdown and gluconeogenesis increases
presence of G6Pase allows glucose export
fatty acids used as an energy source and for ketone body production

18
Q

what are the effects of glucagon on fat and muscle

A

high levels of glucagon causes lipolysis in adipocytes nd proteolysis releasing AA for gluconeogenesis in muscle

19
Q

when is it common to see high levels on glucagon in the blood

A

pathologically during ketoacidosis and sepsis and glucagon normally cleared by the liver

20
Q

what is the structure and function of somatostatin

A

peptide hormone - mostly 28aa in gut
released from D cells of stomach duodenum and pancreas
acts in paracrine - stimulated by lumen H+ and inhibited by ACh
acts on G cells to inhibit the release of gastrin
inhibits release of CCK and secretin as insulin and glucagon if it can get into the cells

21
Q

how does exercise affect blood glucose

A

adrenaline signals via cAMP to enhance glucose production in liver via cori cycle
glycogen breakdown in muscle and GLUT4 insertion via intrinsic AMPK
fatty acid release from adipocytes

22
Q

what is diabetes mellitus

A

failure of insulin action leads to high plasma glucose which is lost in urine taking water with it

23
Q

what are the symptoms of DM

A

polyuria
polydipsia
weight loss blurred vision
ketoacidosis in type 1

24
Q

what is DM type 1 causes and effects

A

primary defect in ability to produce enough insulin
autoimmune disease and B cells destroyed
excess glucagon leads to lipolysis and proteolysis and glluconeogenesis and ketogenesis in the liver

25
Q

what is DM type 2 cause and effect

A

primary defect is an impaired cellular response to insulin - receptor down regulation or reduced signalling
plasma insulin often high and strongly associated with obesity

26
Q

what are the characteristics between type 1 and type 2 DM

A

check photos

27
Q

what is the management of type 1 DM

A

always need insulin
balancing diet and insulin
risk of hypoglycaemia

28
Q

what is the management for type 2 DM

A

diet to reverse problem
drugs to enhance insulin secretion such as sulphonylureas/inretins
drugs to enhance insulin sensitivity - pioglitazone
drugs to inhibit gluconegenesis - metformin