Section 9 part 2 Flashcards
Major factors controlling the release of insulin from β-cells
Major factors controlling insulin secretion
Major factors controlling the release of glucagon from α-cells
What is the longest nerve in our body?
Vagus aka cranial X nerve
Is vagus a motor or a sensory neuron?
Acts as a sensory neuron and as a motor neuron (providing and receiving signals from peripheral organs)
What are the functions of vagus nerve?
v Acts as a sensory neuron and as a motor neuron (providing and receiving signals from peripheral organs)
v Main neuronal coordinator of appetite control, digestion and metabolism
v Release of acetylcholine (cholinergic) in the pancreas stimulates insulin release
Mechanism of insulin release from β-cells
- Uptake of glucose by the type 2 facilitative glucose transporter (Glut 2)
- Aerobic glycolysis and increase of the ATP/ADP ratio.
- Inhibition of ATP-sensitive K+ channels → reduction of K+ efflux → membrane depolarization
- Opening of voltage gated Ca2+ channels (VDCC)
- Increased intracellular Ca2+ triggers exocytosis of insulin containing granules
- Opening of Ca2+ activated potassium channels (K-Ca), leading to the repolarization of the membrane (resetting)
- Metabolic coupling factors generated during glucose metabolism facilitate exocytosis and/or proinsulin synthesis (amplification pathway). Examples are plasma FFA (stimulates exocytosis via G-protein receptor) and intracellularly formed succinate.
- Glucagon-like peptide 1 (GLP-1 from intestine) or related peptides bind to GLP-1 receptors and trigger cAMP production. It potentiates the amplification pathway, ion channels and exocytosis
Regulation of blood glucose post-meal and in fastign state
meal-> increased blood glucose
- this blood glucose is made available for muscle and energy storage as glycogen or TGs
- TGs are made from glucose by the liver-> conversion into glycogen and TGs
- Glucose is also taken up by the adipose tissue and is converted into TGs for energy storage
- glucose is also used by other cells as nerves and RBC
In fasted state
- no glucose
- protien degradation-> AA-> taken by the liver-> gluconeogenesis-> glucose
- Within the liver glycogen is degraded and glucose is released into the circulation
- adipose tissue releases fatty acids through hydrolysis of TGs
- These FA are used by other tissues or are taken up by the liver-> converted into ketone bodies
- ketone bodies are now available as energy
what is the serum glucose level in the fasting state?
3-5 mM
What is the serum, BG in post-prandial state? When does glycosuria start?
Rise to 7 mM after meal (glycosuria if exceeding 10 mM)
What are the anabolic effect of insulin
synthesis of protein, lipid and glycogen and inhibition of their degradation (usage of glucose)
What are the key targets of insulin?
liver, muscle, adipose tissue
Insulin promotes cell __
Insulin promotes cell growth
Glucagon increases many __ processes particularly in the __ (production of __)
Glucagon increases many catabolic processes particularly in the liver (production of glucose)
Which hormone production is stimulated by Neural anticipatory stimulation?
glucagon (subsequently suppressed by insulin)
What is the insulin effect on free fatty acids?
Insulin stimulates lipogenesis and thus decrease free fatty acid.
What is the effect of glucose on GH?
Glucose suppresses GH secretion (remember GH reduces glucose uptake and increases lipolysis)
GLUT functions and locations according to their types?
How does insulin promotes glucose uptake in muscle and adipose tissue?
insulin promotes glucose uptake in muscle and adipose tissue by increasing the Glut 4 transporters on the cell surface
How does insulin promote glucose uptake in the liver?
Insulin promotes glucose uptake in the liver by stimulating glucokinase and thus promote phosphorylation of glucose to form glucose 6-phosphate.
This creates a gradient ad glucose-6-p is stuck in the liver
The concentration gradient of (non-phosphorylated) glucose needed for facilitated uptake via glut 2 is therefore maintained.
what are the pathways triggered by insulin binding? What are the consequences of each pathway?
insulin is RTK-> MAPk and PI3 kinase
PI3K pathway ALLOWS FOR THE MOVEMENT OF GLUT4 from inside the cell to the membrane
MAPk and PI3 kinase also stimulate glycogen synthesis via glycogen synthase activation
Glucagon signalling
Glucagon signals via a GPCR-> PKA or IP3-Ca pathway through adenylyl cyclase or phospholipase C receptively
PKA pathway leads to phosphorylase activation (involved in cleavage of glucose subunits its from glycogen storage; phosphorylase increases glycogenolysis-> increase glucose levels
These pathways also reduce glycolysis and glycogenesis
Glucagon stimulates gluconeogenesis from non-CHO sources especially viia AA metabolism
all this increases glucose available in the liver
Insulin effect on muscles
Insulin stimulates glucose uptkae and consumption
Glucagon effect on the liver
Stimulates glucose synthesis and export
Insulin and glucagon effects on the adipose tissue
Insulin: ↑ Triacylglycerol synthesis
Glucagon: ↑ Fatty acid mobilization
Glucagon effects in the muscle
glucagon receptors are not expressed in muscles-> no effect of glucagon on muslce
Endocrine functions of insulin
Endocrine functions of glucagon & GLPs
on islet cells, liver, stomach, intestine, brain
Mechanisms of diabetes mellitus Type I
- beta cells are destroyed by misguided immune cells
- Autoantibodies from CD4+ and CD8+ T-cell
- >40 different genetic loci
- Human leukocyte antigen locus confer strongest risk
- Not purely genetic as monozygotic twins have <50% risk
- Viral induced beta cell destruction
- Enterovirus, Rotavirus, Mumpsvirus and Cytomegalovirus
Mechanisms of diabetes mellitus Type II Insulin resistance
- Pre-receptor
- Autoantibodies against insulin
- Mutant insulin (missing orretained peptide)
- Receptor
- Low number or affinity
- Autoantibodies against the receptor
- Post-receptor
- Deficient signal mediators
- Low expression of Glut4
How does Obesity predispose Type II diabetes
Source and function of Somatostatin; type of hormone
receptors and isoforms
an inhibitor of many hormones
Peptide
Released by many cell types. Main source of circulating hormone is the GI tract and the pancreatic D cells.
Five different receptors.
Two somatostatin isoforms.
Somatostatin’s effect on pituitary, Peripheral and central nervous system, Gastrointestinal tract and pancreas
- Pituitary: Negative regulation of GH release
- Peripheral and central nervous system: Neuromodulatory effects
- Pancreas: Inhibitor of insulin and glucagon secretion acts in in a paracrine fashion
- Gastrointestinal tract: Inhibitor of the release of many GI hormones. Additional direct inhibitory effects on GI functions.
Pancreatic polypeptide (PP)
function
- Reduces appetite
- Powerful inhibitor of the secretion of digestive enzymes of the pancreas
- Blocks contraction of the gall bladder (inhibitor of bile secretion)
Pancreatic polypeptide (PP): where and when is it released
- By F-cells of the pancreas (or PP cells)
Gastrointestinal Hormones: site of production and effect
Types and action of gastrointestinal hormones
