Insulin Secretion and Intermediary Metabolism Flashcards
Basic feedback loop of blood glucose-affecting hormones?
Increased blood glucose concentration
Increased insulin secretion response
Decreased blood glucose concentration
Increased secretion of glucagon, catecholamines, somatotrophin, cortisol to raise it again
Percentage of pancreas involved in exocrine and endocrine function?
Exocrine = 98% (into duct) Endocrine = 2% (into circulation)
Name of pancreatic tissue associated with endocrine secretion?
Islets of Langerhans
Which 3 cell types lie in the Islets of Langerhans and what hormones do they produce?
Alpha cells - glucagon
Beta cells - insulin
Delta cells - somatostatin
How can cells within the islets of langerhans demonstrate paracrine control?
The cells are very close together with small gaps between them. These gaps have high hormone concentrations and allow communication between the different cells.
Gap junctions allow small molecules to pass directly between cells and tight junctions for small intercellular space
Other than somatotrophin release, what does somatostatin inhibit?
Insulin AND glucagon release via paracrine effects
Main stimulus of insulin release?
Increased blood glucose
Other stimuli of insulin release?
Glucagon release
Certain GI hormones
Certain amino acids
Parasympathetic nervous activity
Inhibitory stimuli of insulin release?
Sympathetic activity
Somatostatin
What main effects does increased insulin release have?
Increased glycogenesis
Increased glycolysis
Increased glucose transport INTO cells via GLUT4
OVERALL decrease in blood glucose conc
Other effects of insulin release? (still aim of reducing blood glucose)
Increased amino acid transport
Increased protein synthesis
Decreased lipolysis
Increased lipogenesis
Main stimulus of glucagon release?
Decreased blood glucose
Other stimuli of glucagon release?
Certain GI hormones
Certain amino acids
Sympathetic activity
Inhibitory stimuli of glucagon release?
Beta cells secreting insulin
Parasympathetic nervous activity
Somatostatin
Main effect of increased glucagon secretion?
Hepatic glycogenolysis
Other effects of glucagon release?
Increased amino acid transport into liver for gluconeogenesis
Increased lipless for gluconeogenesis
OVERALL increases blood glucose conc
Role of glucokinase in insulin release?
Converts glucose to glucose-6-phosphate, consumption of G6P increases ATP concentration in beta cell leading to insulin release
Process of insulin synthesis?
Proinsulin cleaved to form C-peptide + alpha/beta chains of insulin
Disulphide bridges form specific 3D structure of insulin
Levels of what can be measured to assess pancreatic function?
C-PEPTIDE
Process of beta cell stimulation and insulin release?
Glucose enters via GLUT2 transporter
Glucose is converted by hexo/glucokinase to G6P and ATP
ATP blocks ATP-sensitive K+ channels
VG Ca2+ channels open causing influx of Ca2+ into beta cell stimulating release of preformed insulin and synthesis of NEW insulin
Does oral glucose load impact or intravenous glucose load impact insulin production more?
Oral glucose load has a greater impact on insulin production
What is GLP-1, why is it released and what effects does it have?
Glucagon-like peptide 1
GI hormone released in response to food
Causes insulin release and decrease in glucagon release
Increases SATIETY so less food is consumed, can be used to help weight loss
What is a common T2DM treatment involving GLP-1?
Injected GLP-1 and DPPG-4 inhibitor
DPPG-4 usually breaks down GLP-1 so inhibitor extends the half-life and effect of GLP-1
What are the two phases of insulin release?
First phase insulin - stored insulin which is released directly after consuming a meal
Second phase insulin - newly synthesised insulin, released over a couple of hours and increases food storage (glycogenesis)
What is the structure of the insulin receptor?
2 cytoplasmic alpha subunits - bind to insulin
2 transmembrane beta subunits - TYROSINE KINASE domains
What is the process of inducing insulin’s effects on target cell by binding to its receptor?
Inuslin binds to alpha subunits
Conformational change in tyrosine kinase domains
Autophosphorylation of receptors occurs
Conformational change induces phosphorylation of cell protein substrates and activation of pathways leading to known insulin effects (glycogenesis, protein synthesis etc.)
Type 2 diabetes mellitus patients have their abnormality in insulin production, the receptor, or the intracellular pathway?
Type 2 patients are INSULIN RESISTANT.
The abnormality lies in the pathways of insulin action, not the receptor.
