Glucose & homeostasis Flashcards
Which glucose concentrations cause an impact on cerebral function?
<4-5mmol
Which glucose concentrations result in coma, and ultimately death?
<2mmol/L
What function is performed by glucagon?
Increases hepatic glucose output for circulation
Increases glycogenolysis and gluconeogenesis
Inhibits glycolysis and glycogenesis
Inhibits insulin
What is hepatic glucose output?
Glycogenolysis
Gluconeogenesis
How does cortisol and catecholamines influence glucose regulation?
Secreted by the adrenal glands, enhances glucose production through gluconeogenesis, glycogenolysis, and lipolysis
What effect does growth hormone have on insulin?
Inhibitory-it suppresses the effects
What effect does insulin have?
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
Which form of diabetes is most common?
Type 2 diabetes mellitus
Which type of gland is the pancreas?
Retroperitoneal gland
What type of cells make up the pancreas?
Acinar cells (majority) Islets of langerhans
What is the function of acinar cells?
Secrete pancreatic juice composed of digestive enzymes and bicarbonate
Which cells secrete glucagon?
Alpha cells of the islets of Langerhans
Why is glucagon secreted?
Secreted in response to hypoglycaemia, prolonged fasting, exercise and protein rich meals
How is glucagon released?
Exocytosis from stored peptide vesicles initiated by secretary stimuli of alpha cells of the islets of langerhans
What are the stimulatory regulators of glucagon release?
Hypoglycaemia, amino acids, and glucose-dependent insulinotropic peptide (GIP)
Which factors inhibit glucagon release?
Hyperglycaemia
Paracrine effects by insulin
Glucagon like peptide-1
Which types of junctions are present with the islets of Langerhans?
Gap and tight junctions
Which glucose transporter is found in alpha cells?
GLUT-1 co -transporter
What is the mechanism of action for glucagon secretion?
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
What are the 5 stages of insulin secretion from beta cells?
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
Which cells secrete insulin?
Beta cells of the islets of Langerhans
Which hormone inhibits the secretion of insulin?
Somatostatin
Which type of autonomic innervation increases insulin secretion?
Parasympathetic innervation
Which subunits form the insulin receptor?
2 alpha and 2 beta subunits, linked by disulphide bonds
Which insulin receptor subunits are extracellular?
alpha subunits, enclose the insulin binding domains
Describe the structure of an insulin receptor?
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
Upon insulin binding what occurs to the insulin receptor?
Conformational change occurs to the tyrosine kinase domain of b sub units this causes autophosphorylation, activates the receptor to phosphorylate intracellular target proteins
Which type of glucose co transporters are synthesised in response to insulin, in adipose, and muscle cells?
GLUT-4, those residing within vesicles rapidly fuse and insert into plasma membrane
What is the function of GLUT-4 glucose co transporters?
Enables facilitated diffuse of glucose into muscle and adipose tissue
What effects does insulin have on the liver?
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
What effect does insulin have on adipose tissue?
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
Which enzymes does insulin inhibit within adipose tissue?
Lipases that hydrolyseds triglycerides within adipocytes
What effect does glucagon have on adipose tissue?
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
Where can ketone bodies be used?
Brain, muscle tissue
What is the main product of beta-oxidation?
Acetyl-CoA
Why cannot acetyl-CoA enter the TCA cycle during hypoglycaemia?
Insufficient oxaloacetate under hypoglycaemia, used for gluconeoegensis
hence acetyl-CoA undergoes thiolysis reactions to form acetoacetyl-CoA, and addition into HMG-CoA
Which enzymes are activated by glucagon within adipocytes?
Hormone sensitive lipase, increases FFA for beta oxidation, and inhibits acetyl-CoA carboxylase to enable FA passage into mitochondria by carnitine shuttles
What is produced by proteolytic cleavage of proinsulin?
Equimolar concentrations of c-peptide and insulin
Which parameter is used to monitor insulin production?
C-peptide test
What is the incretin effect?
Defined as the increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose
Which cells secrete GLP-1?
Endocrine L cells by differential processing of proglucagon
Intestinal epithelial
What effect does GLP-1 exert?
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
Why does glp-1 have a short half life?
Due to rapid degradation from enzyme dipeptidyl peptidase-4
How can GLP-1 be used for treatment of diabetes mellitus?
Administer injections to individuals to promote insulin secretion, in addition to promote satiety, thus regulating the control of glucose levels
What is the first phase insulin release?
In response to a glucose load, there is a release of stored insulin, and synthesis of insulin is initiated.
How is FPIR impacted with Type-2 diabetes?
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
