Control of blood glucose and endocrine pancreas Flashcards
(38 cards)
“Describe the transport mechanism and transporters used for
glucose to get into cells?”
“Occurs via secondary active transport using Sodium-glucose cotransporters (SGLTs)
“
State the 2 types of SGLTs with functions?
“SGLT1 and SGLT2
SGLT1: glucose absorption from gut
SGLT1, SGLT2: glucose reabsorption from kidney (PCT)
“
“State the members of the family of GLUTs with location, affinity for
glucose and feature?”
"GLUT 1 (brain, erythrocytes) – high affinity for glucose: constant uptake of glucose at 2-6 mM GLUT 2 (liver, kidney, pancreas, gut) – low affinity: glucose equilibrates across membrane GLUT 3 (brain) – high affinity GLUT 4 (muscle and adipose tissue) – medium affinity. Insulin recruits transporters
”
What does affinity of a GLUT transporter determine?
“Affinity of the GLUT transporter will determine the rate at which glucose enters the cell depending on ECF glucose conc.
“
What are GLUT 1 and GLUT 2 major role?
“Glucose-dependent insulin release in pancreas
“
What are GLUT 3 and GLUT 4 major role?
“Insulin-dependent uptake of glucose into cells
“
What are the islets of langerhans?
“Clusters of endocrine cells surrounded by exocrine pancreas
“
“State the 3 types of endocrine cells found on the pancreas with their
hormone secretion named?”
“α-cells (A cells): glucagon
β-cells (B cells): insulin
δ-cells: somatostatin
“
What occurs to proinsulin once it is transferred to the golgi apparatus?
“Peptidases break off the C peptide leaving an A and B chain linked by disulphide bonds
- This forms mature insulin
One mole of C-peptide is secreted for each mole of insulin
Describe the release of insulin into the circulation?
“1) Pancreas supplied by branches of the coeliac, superior mesenteric, and splenic arteries.
2) The venous drainage of the pancreas is into the portal system (towards liver)
3) Half of the secreted insulin is metabolized by the liver in it’s first pass;
the remainder is diluted in the peripheral circulatio1n
“
What can be used as good index of insulin secretion?
“C-peptide within the peripheral circulation
- As its not metabolized by liver
One mole of C-peptide is secreted for each mole of insulin
“
State factors which regulate insulin secretion and categorise them?
“These stimulate beta cells (of islets of langerhans):
- Incretin
- Plasma glucose
- AA
- Glucagon
- Parasympathetic excitation
These inhibit beta cells (of islets of langerhans):
- Somatostatin
- Alpha-adrenergic
Others which regulate
- Paracrine effects of other islet hormones”
State factors which regulate glucagon secretion and categorise them?
“These stimulate alpha cells (of islets of langerhans):
- AA
- Beta-adrenergic
- Parasympathetic
These inhibit alpha cells (of islets of langerhans):
- Somatostatin
- Insulin
- Plasma glucose
“
Describe the insulin/glucagon ratio over a range of glucose conc.
“Insulin / glucagon ratio varies over physiologically significant range of glucose concentrations
- The ratio of insulin/glucagon increases as plasma glucose increases, and decreases as it decreases.
“
How does insulin/glucagon briefly maintain glucose homeostasis
“Glucagon and insulin are both active over physiol glucose range
continual balance between these opposing hormones that maintains glucose homeostasis.
“
“State the mechanism as to how Beta-cells sense a rise in glucose and
therefore release insulin?”
”- GLUT2 is used as a sensor on the cell- takes up glucose
- Glucose entry causes ATP production via glycolysis and TCA (glucose oxidation)
- Rise in ATP due to glucose oxidation causes closure of K channel
- Increases Ca entry
- Increasing intracellular Ca is the signal that triggers insulin exocytosis”
What member is the insulin receptor part of?
“Tyrosine kinase superfamily
- disulfide-linked tetramer with the β-subunits spanning the membrane and the α-subunits located on the exterior surface.
“
What occurs once insulin binds to its receptor?
”- Activates cascade of protein phosphorylation, which stimulate or inhibit specific metabolic enzymes by modulating enzyme phosphorylation e.g. causes glycogen synthesis, glycolysis
- Modulates activity of metabolic enzymes by regulating gene transcription
“
Describe how insulin binding leads to promotion of lipogenesis?
“Insulin binding leads to a decrease in cAMP levels, reducing PKA activity (less phosphorylation), releasing ACC (acetyl-coA carboxylase) from inhibition, thereby promoting lipogenesis.
“
Describe glucagon receptor action?
“Activates Galpha pathway (cAMP->PKA). PKA phosphorlyates many substrates
Enzymes involved:
- glycogen synthase is activated by dephosphorylation
- glycogen phosphorylase is activated by phosphorylation. “
“Which activity do counter-regulatory hormones act through to
phosprylate key enzymes?”
“Counter-regulatory hormones act principally (not exclusively) through activity of PKA
, which phosphorylates key enzymes in metabolic pathways
“
What does insulin action cause to key enzymes of metabolic pathways?
Dephosphorylation
How is type 1 diabetes mellitus caused by?
“Destruction of insulin-producing pancreatic beta cells
- leads to deficiency of insulin
“
What symptom is central to diagnosis of diabetes mellitus?
Hyperglycemia
