Physiology: endocrine pancreas Flashcards
Endocrine Pancreas
Refers to cells within the pancreas that synthesise and secrete hormones
–> Islets of Langerhans
Main Endocrine pancreas hormones
Insulin
Glucagon
Somatostatin
Beta-cells
Responsible for secreting insulin
Beta cell and T1DM and T2DM
Beta-cell failure occurs in both type 1 and type 2 diabetes
Type 1
- Autoimmune destruction. of beta cells.
- Insulin insufficiency
Type 2
- Insulin resistance and beta-cell dysfunction
Process of metabolic disease. involving beta-cells
- Glucose Tolerant
- Obese/ Insulin Resistant
- Insulin resistant with B-cell compensation
- B-cell failure
- Overt T2DM
Beta-cell and glucose homeostasis
Beta-cell compensation= glucose homeostasis
Beta cell defect relative to insulin demand= hyperglycaemia
Essential Molecular Components of Glucose Sensing (6)
Glucose Transporters (GLUT 1 & 2) Glucokinase (GCK) Oxidative Metabolism Katp Channels L-type voltage dependent Ca2+ channels Exocytotic machinery
basal Blood Glucose (<5.5mM) in beta-cell
Glucose is taken up by GLUT 1 or. 2
Acted on by glucokinase
Glycolysis occurs (Glucose–> Pyruvate)
Pyruvate goes through mitochondria to release ATP
(not sufficient ATP to close Katp channel)
K leaves cell through Katp channel
Membrane hyper-polarisation
Stimulatory blood glucose (>5.5mM) in beta-cell
Glucose uptake by GLUT 1 or 2
Acted on by glucokinase
Glycolysis occurs (Glucose –> Pyruvate)
Pyruvate converted to ATP by mitochondria
Sufficient Alp to close Katp channel
Results in membrane depolarisation
Opening of voltage-dependent calcium channel.
Influx of calcium
Results in release of insulin (exocytosis)
Alpha cells
Operate counter-regulatory to beta-cells
Secrete glucagon inversely proportional to blood glucose.
Glucagon action
Acts on the liver to promote hepatic glucose production.
Raises blood glucose
Glucagon secretion in T2DM
Glucagon secretion is elevated in fed state.
Contributes to hyperglycaemia
Glucagon: Low glucose
Glucose uptake and metabolism low
Katp channels open
Voltage gated sodium channels contribute to action potentials
P/Q type voltage-gated calcium channels enable calcium influx
Glucagon exocytosis triggered
Acts. on the liver to promote hepatic glucose production
–> Raises blood glucose
Glucagon: High Glucose
Glucose uptake and metabolism high
Katp channel closed
Cell is depolarised
Presence of SGLT2 glucose transporters contributes to non-voltage-regulated sodium ion influx
Na and Ca channels closed
–> Glucagon is not exocytosed (does not further raise blood glucose)
Glucagon and Glucose Homeostasis (fasted state0
Fasted
- alpha cells release glucagon
- glucagon acts on the liver to promote hepatic glucose production
- raises blood glucose
- glucose can be utilised by muscles
