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

Increases hepatic glucose output for circulation
Increases 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

Inhibitory-it suppresses the effects

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7
Q

What effect does insulin have?

A
Increased protein synthesis
Increased lipogenesis
Increased Hepatic glycogenesis
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

Retroperitoneal 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 acinar 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