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BRS (RF) > Glucose & homeostasis > Flashcards

Glucose & homeostasis Flashcards

1
Q

Which glucose concentrations cause an impact on cerebral function?

A

<4-5mmol

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2
Q

Which glucose concentrations result in coma, and ultimately death?

A

<2mmol/L

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3
Q

What function is performed by glucagon?

A

Controls plasma glucose concentrations during period of increased glucose demands, by increasing hepatic glucose output for circulation
Promotes hepatic conversion of glycogen to glucose (glycogenolysis) and gluconeogenesis
Inhibits glycolysis and glycogenesis

Inhibits insulin

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4
Q

What is hepatic glucose output?

A

Glycogenolysis

Gluconeogenesis

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5
Q

How does cortisol and catecholamines influence glucose regulation?

A

Secreted by the adrenal glands, enhances glucose production through gluconeogenesis, glycogenolysis, and lipolysis

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6
Q

What effect does growth hormone have on insulin?

A

Counteracts the effects

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7
Q

What effect does insulin have?

A 
Increased protein synthesis
Increased lipogenesis
Increased Hepatic glycogenogenesis 
Increased glucose uptake
Increased glycolysis 
Inhibition of glucagon, inhibition of lipolysis, inhibition of HGO, inhibition of glucagon secretion
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8
Q

Which form of diabetes is most common?

A

Type 2 diabetes mellitus

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9
Q

Which type of gland is the pancreas?

A

Rectoperineal gland

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10
Q

What type of cells make up the pancreas?

A 
Acinar cells (majority)
Islets of langerhans
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11
Q

What is the function of acing cells?

A

Secrete pancreatic juice composed of digestive enzymes and bicarbonate

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12
Q

Which cells secrete glucagon?

A

Alpha cells of the islets of Langerhans

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13
Q

Why is glucagon secreted?

A

Secreted in response to hypoglycaemia, prolonged fasting, exercise and protein rich meals

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14
Q

How is glucagon released?

A

Exocytosis from stored peptide vesicles initiated by secretary stimuli of alpha cells of the islets of langerhans

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15
Q

What are the stimulatory regulators of glucagon release?

A

Hypoglycaemia, amino acids, and glucose-dependent insulinotropic peptide (GIP)

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16
Q

Which factors inhibit glucagon release?

A

Hyperglycaemia
Paracrine effects by insulin
Glucagon like peptide-1

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17
Q

Which types of junctions are present with the islets of Langerhans?

A

Gap and tight junctions

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18
Q

Which glucose transporter is found in alpha cells?

A

GLUT-1 co -transporter

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19
Q

What is the mechanism of action for glucagon secretion?

A

Hypoglcycaemia stimulates pancreatic alpha cells to release glucagon

Intracellular ATP level is proportional and reflects the plasma glucose levels
Hypoglycaemia = Low intracellular ATP
Close-ATP sensitive potassium ion channels, reduces efflux of potassium ions, this causes depolarisation of the cell membrane, opening voltage dependent Ca2+ channels, allows influx of Ca2+

Increase in intracellular calcium triggers exocytosis of glucagon granules from alpha cells

20
Q

What are the 5 stages of insulin secretion from beta cells?

A

Regulated by facilitated diffusion of glucose by glut-2 co transporters
2) Glucose is phosphorylated to glucose-6-phosphate by glucokinase, metabolised to ATP by glycolysis

3) Elevation in ATP:ADP ratio induces closure of cell-surface sensitive K+ channels, leading to cell membrane depolarisation
4) Cell-Surface voltage dependent calcium channels (VDCC) open, facilitating extracellular calcium influx into the beta cell
5) Influx in cytosolic calcium triggers the exocytosis of insulin from secretory vesicles

21
Q

Which cells secrete insulin?

A

Beta cells of the islets of Langerhans

22
Q

Which hormone inhibits the secretion of insulin?

A

Somatostatin

23
Q

Which type of autonomic innervation increases insulin secretion?

A

Parasympathetic innervation

24
Q

Which subunits form the insulin receptor?

A

2 alpha and 2 beta subunits, linked by disulphide bonds

25
Q

Which insulin receptor subunits are extracellular?

A

alpha subunits, enclose the insulin binding domains

26
Q

Describe the structure of an insulin receptor?

A

Consists of 2 alpha and 2 beta subunits, the extracellular alpha chains are linked to the insulin binding domains - linked beta chains penetrated the plasma membrane. Associated to tyrosine kinase domains

27
Q

Upon insulin binding what occurs to the insulin receptor?

A

Conformational change occurs to the tyrosine kinase domain of b sub units this causes autophosphorylation, activates the receptor to phosphorylate intracellular target proteins

28
Q

Which type of glucose co transporters are synthesised in response to insulin, in adipose, and muscle cells?

A

GLUT-4, those residing within vesicles rapidly fuse and insert into plasma membrane

29
Q

What is the function of GLUT-4 glucose co transporters?

A

Enables facilitated diffuse of glucose into muscle and adipose tissue

30
Q

What effects does insulin have on the liver?

A

Stimulates glycogenesis, glucose is taken up by hepatocytes through a series of condensation reactions and formation of glycosidic bonds, glucose storage polymer, glycogen is synhesised

Hexokinase is activated to phosphorylate glucose into glucose-6-phosphate (entrapping it within the cell)

Decreased hepatic glucose output

31
Q

What effect does insulin have on adipose tissue?

A

Lipogenesis and inhibition of lipolysis

Glucose entry within adipocytes can be used to synthesis glycerol, that form ester linkages with fatty acids delivered from the liver to form triglycerides

32
Q

Which enzymes does insulin inhibit within adipose tissue?

A

Lipases that hydrolyseds triglycerides within adipocytes

33
Q

What effect does glucagon have on adipose tissue?

A

Promotes formation of ketone bodies and lipids. Lipids are hydrolysed into fatty acids utilised for beta oxidation to generate acetyl-CoA substrates, these intermediates are reduced to generate ATP within the tea cycle, or under ketogenesis

Inhibits de-novo lipogenesis bu inactivating the enzyme that catalyses the initial step in fatty acid synthesis

34
Q

Where can ketone bodies be used?

A

Brain, muscle tissue

35
Q

What is the main product of beta-oxidation?

A

Acetyl-CoA

36
Q

Why cannot acetyl-CoA enter the TCA cycle during hypoglycaemia?

A

Insufficient oxaloacetate under hypoglycaemia, used for gluconeoegensis
hence acetyl-CoA undergoes thiolysis reactions to form acetoacetyl-CoA, and addition into HMG-CoA

37
Q

Which enzymes are activated by glucagon within adipocytes?

A

Hormone sensitive lipase, increases FFA for beta oxidation, and inhibits acetyl-CoA carboxylase to enable FA passage into mitochondria by carnitine shuttles

38
Q

What is produced by proteolytic cleavage of proinsulin?

A

Equimolar concentrations of c-peptide and insulin

39
Q

Which parameter is used to monitor insulin production?

A

C-peptide test

40
Q

What is the incretin effect?

A

Defined as the increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose

41
Q

Which cells secrete GLP-1?

A

Endocrine L cells by differential processing of proglucagon

Intestinal epithelial

42
Q

What effect does GLP-1 exert?

A

Insulin secretion from beta cells, and to inhibit glucagon secretion.
Inhibits gasointestinal motley and secretion, thus acts as an enterogastrone and part of the ideal brake mechanism

Promotes satiety

43
Q

Why does glp-1 have a short half life?

A

Due to rapid degradation from enzyme dipeptidyl peptidase-4

44
Q

How can GLP-1 be used for treatment of diabetes mellitus?

A

Administer injections to individuals to promote insulin secretion, in addition to promote satiety, thus regulating the control of glucose levels

45
Q

What is the first phase insulin release?

A

In response to a glucose load, there is a release of stored insulin, and synthesis of insulin is initiated.

46
Q

How is FPIR impacted with Type-2 diabetes?

A

Less stored insulin within beta cells of the islets of Langerhans, coupled with insulin resistance (to counteract against increased glucose load)
Do not express prominent FPIR, insulin synthesis is required

BRS (RF) (38 decks)

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