Glucose & homeostasis

Question 1

Which glucose concentrations cause an impact on cerebral function?

Answer 1

<4-5mmol

Question 2

Which glucose concentrations result in coma, and ultimately death?

Answer 2

<2mmol/L

Question 3

What function is performed by glucagon?

Answer 3

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

Question 4

What is hepatic glucose output?

Answer 4

Glycogenolysis

Gluconeogenesis

Question 5

How does cortisol and catecholamines influence glucose regulation?

Answer 5

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

Question 6

What effect does growth hormone have on insulin?

Answer 6

Counteracts the effects

Question 7

What effect does insulin have?

Answer 7

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

Question 8

Which form of diabetes is most common?

Answer 8

Type 2 diabetes mellitus

Question 9

Which type of gland is the pancreas?

Answer 9

Rectoperineal gland

Question 10

What type of cells make up the pancreas?

Answer 10

Acinar cells (majority)
Islets of langerhans

Question 11

What is the function of acing cells?

Answer 11

Secrete pancreatic juice composed of digestive enzymes and bicarbonate

Question 12

Which cells secrete glucagon?

Answer 12

Alpha cells of the islets of Langerhans

Question 13

Why is glucagon secreted?

Answer 13

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

Question 14

How is glucagon released?

Answer 14

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

Question 15

What are the stimulatory regulators of glucagon release?

Answer 15

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

Question 16

Which factors inhibit glucagon release?

Answer 16

Hyperglycaemia
Paracrine effects by insulin
Glucagon like peptide-1

Question 17

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

Answer 17

Gap and tight junctions

Question 18

Which glucose transporter is found in alpha cells?

Answer 18

GLUT-1 co -transporter

Question 19

What is the mechanism of action for glucagon secretion?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

Which cells secrete insulin?

Answer 21

Beta cells of the islets of Langerhans

Question 22

Which hormone inhibits the secretion of insulin?

Answer 22

Somatostatin

Question 23

Which type of autonomic innervation increases insulin secretion?

Answer 23

Parasympathetic innervation

Question 24

Which subunits form the insulin receptor?

Answer 24

2 alpha and 2 beta subunits, linked by disulphide bonds

Question 25

Which insulin receptor subunits are extracellular?

Answer 25

alpha subunits, enclose the insulin binding domains

Question 26

Describe the structure of an insulin receptor?

Answer 26

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

Question 27

Upon insulin binding what occurs to the insulin receptor?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

Enables facilitated diffuse of glucose into muscle and adipose tissue

Question 30

What effects does insulin have on the liver?

Answer 30

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

Question 31

What effect does insulin have on adipose tissue?

Answer 31

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

Question 32

Which enzymes does insulin inhibit within adipose tissue?

Answer 32

Lipases that hydrolyseds triglycerides within adipocytes

Question 33

What effect does glucagon have on adipose tissue?

Answer 33

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

Question 34

Where can ketone bodies be used?

Answer 34

Brain, muscle tissue

Question 35

What is the main product of beta-oxidation?

Answer 35

Acetyl-CoA

Question 36

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

Answer 36

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

Question 37

Which enzymes are activated by glucagon within adipocytes?

Answer 37

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

Question 38

What is produced by proteolytic cleavage of proinsulin?

Answer 38

Equimolar concentrations of c-peptide and insulin

Question 39

Which parameter is used to monitor insulin production?

Answer 39

C-peptide test

Question 40

What is the incretin effect?

Answer 40

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

Question 41

Which cells secrete GLP-1?

Answer 41

Endocrine L cells by differential processing of proglucagon Intestinal epithelial

Question 42

What effect does GLP-1 exert?

Answer 42

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

Question 43

Why does glp-1 have a short half life?

Answer 43

Due to rapid degradation from enzyme dipeptidyl peptidase-4

Question 44

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

Answer 44

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

Question 45

What is the first phase insulin release?

Answer 45

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

Question 46

How is FPIR impacted with Type-2 diabetes?

Answer 46

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