Flashcards in Gut Hormones Deck (67):
What is central to many metabolic pathways?
Which cells/organs are dependent on glucose?
Neurons, RBC and the brain
What is used as an energy source in a starvation state?
Fat will be converted to ketones by lipolysis as an alternative energy source to glucose
Between meals where is blood glucose from?
Depending on the frequency of snacking, glycogenolysis and gluconeogenesis may be more or less active
When is gluconeogenesis the main source of blood glucose?
Late at night or early in the morning (fasting state)
How are glucose levels maintained?
Glucose levels are regulated by hormones that affect appetite and cell metabolism
Which are the major hormones that control blood glucose?
Insulin and glucagon are the first responses to glucose
Insulin is the only hormone which acts to lower blood glucose
What are some other hormones that help regulate blood glucose?
Epinephrine, cortisol, GH, thyroid hormone, secretin, cholecytokinin
All of these hormones (including glucagon) act at the same time and form an integrated control system)
Which receptors are glucagon and epinephrine linked to?
Linked to G-proteins
Which receptor is insulin bind to?
Receptors with intrinsic tyrosine kinase activity
How is enzyme activity regulated?
Through phosphorylation (posphokinases) and dephosphorylation (phosphatases), switching between active and inactive state, activation cascade
What is the fucntion of GI tract hormones?
To regulate activity of the stomach, intestine and pancreas (in addition to the regulation of blood glucose)
Where else can GI hormones be found?
Central or peripheral nervous system
- somatostatin, gastrin, CCK, vasointestinal peptide, insulin ,calcitonin)
Where are the GI hormones produced?
Produced in the cell body of neurons
They may modulate signal transmission
What is the most common endocrine disorder?
- symptoms: loss of weight, polydipsea, polyuria, polyphagia
What did Minkowski discover?
The abnormalities of the islets of Langerhans
What did Banting and Best do?
They isolated insulin and show that it lowers blood glucose in dogs
How much do islets of Langerhans weigh?
1 -2 g
What does the exocrine pancreas secrete? and where do they secrete enzymes to?
They secrete a digestive juice composed of digestive enzymes secreted by the acinar cells and aqueous NaHCO3 secreted by the duct cells
What does the endocrine pancrease secrete?
Insulin and glucagon into the blood
What do acinar cells secrete?
Digestive enzymes: proteases, amylase, lipase
What do duct cells secrete?
What cells do the Islet of Langerhans have?
- a-cells: glucagon
- b-cells: insulin
- d-cells: somatostatin
- f-cells: pancreatic polypeptide
Are islet cells vascularized?
islets are highly vascularized - 5 to 10x blood flow of exocrine pancreas
Where are the blood supplies centrally located?
In the b-cells, insulin detects glucose levels then blood travels to more peripheral A and D cells
What is glucagon also produced as?
Preproglucagon processed to proglucagon to glucagon
How does the body response to an increase in blood glucose?
- a-cells will decrease glucagon
- b-cells will increase insulin
- both processed will decrease blood glucose levels to normal
What is the vagus nerve?
Longest nerve in the body
acts as a sensory neuron and a motor neuron
What is the function of the vagus nerve?
Main neuronal coordinator of appetite control, digestion and metabolism
Release of acetylcholine in the pancreas stimulates insulin release
What does an increase in blood glucose concentration trigger?
- Islet b-cells will trigger an release of insulin to lower blood glucose, blood FA, blood AA
- increase in protein synthesis and fuel storage
- increase in GI hormones from food intake
- parasympathetic stimulation of islet b cells
How is insulin released from B cells?
- Uptake of glucose by GLUT 2
- Aerobic glycolysis and increase of ATP/ADP ratio
- Inhibition of K-ATP channels, reduction of K efflux, membrane depolarization
- Opening of Ca2+ channels: exocytosis of insulin containing granules
- Opening of Ca2+ activated K channels (repolarization of the membrane)
What does GLP-1 stimulate?
GLP-1 binds to receptors and trigger cAMP production. It potentiates the amplification pathway, ion channels and exocytosis
What is the fasting glucose level?
3 -5 mmol/L
What are the anabolic effects of insulin?
- protein synthesis
- lipid and glycogen synthesis
- inhibition of their degradation
Where are the key target cells of insulin?
Liver, muscle, adipose tissue
What does insulin promote?
Insulin is essential for normal growth and development, insulin promotes cell growth
What does glucagon increase?
Glucagon increases many catabolic processes particularly in the liver - production of glucose
Why is insulin always secreted?
Insulin is continuosly secreted to enable peripheral tissues to uptake glucose
What does glucose suppress?
Glucose suppresses GH secretion - and increases lipolysis
Where are the major sites of expression of GLUT 2?
B cells of islets, liver, epithelial cells of small intestine, kidneys
What is the function of GLUT2?
B cell glucose sensor, transport out of intestinal and renal epithelial cells
What is the function of GLUT 4?
Insulin-stimulated glucose uptake
What are the major sites of expression of GLUT4?
Skeletal and cardiac muscle, adipose tissue, other tissues
How does insulin stimulate the uptake of glucose?
By stimulating glucokinase and promote phosphorylation of glucose to form glucose-6-phosphate.
The conc gradient of glucose is needed for faciliated uptake via GLU2
Can insulin bind to other receptors?
Insulin can bind to insulin receptors, IGF-1 and IGF-II receptors
What does of insulin trigger?
Activation of the insulin receptor causes activation of phosphoinositide 3 kinase, which speeds the translocation of the GLUT 4 containing endosomes into the cell membrane.
How many membrane domain does GLUT 4 span through?
12 membrane spanning domains
How is glucagon signaling initiated?
- glucagon binds to a G coupled protein receptor which results in a change in conformation of the receptor
- allow GTP/GDP exchange
- the free alpha subunit actiates adenylate cyclase
- cAMP binds regulatory subunitsto increase PKA
- increases glycogenolysis and gluconeogenesis
- decrease glycogenesis and glycolysis
What is the influence of insulin and glucagon on glucose metabolism?
Insulin: increases triacylglycerol synthesis
Glucagon: increase FA mobilization
What are the endocrine effects of insulin on the liver?
- reversal of catabolic features of insulin deficiency
- inhibits glycogenolysis
- inhibits conversion of FA and AA to keto acids
- promotes glucose storage as glycogen
What are the endocrine effects of insulin on muscles?
- increased protein synthesis
- increased AA transport
- increases ribosomal protein synthesis
- increases glucose transport
- induces glycogen synthetase and inhibits phosphorylase
What are the endocrine effects of insulin on adipose tissue?
- increases TG storage
- glucose tranport into cell provides glycerol phosphate to permit esterification of FA supplied by lipoprotein transport
What effect does GLP-1 have on the brain?
What does glucagon affect in the islet cells and liver?
Islet: stimulates insulin secretion
Liver: stimulates glucogenolysis, glucogenesis, FA oxidation and ketogenesis
inhibits glucogen synthesis and FA synthesis
What are the effects of insulin on ion transport?
insulin increases K intake into cells
- possible mechanis: activation of the Na/K pump
- glucose and insulin relieve hyperkalemia
Changes in Ca flux
- increase of Ca in mitochondria
What are the four most common weight loss surgery procedures?
- adjustable gastric band
- roux-en-Y gastric bypass
- duodenal switch
- vertical sleeve gastrectomy
What is somatostatin?
An inhibitor of many hormones
- pituatary: negative release of GH release
- peripheral and CNS: neuromodulatory effects
- GI tract: inhibitor of the release of many GI hormones
- pancrease: inhibitor of insulin and glucagon secretion
What is the function of pancreatic polypeptide?
- reduces appetite
- inhibits the secretion of digestive enzymes of the pancreas
- blocks contraction of the gall bladder: inhibitor of bile secretion
What regulates pancreatic polypeptide?
It may increase by vagus nerve and CCK in response to a meal
not dependent on glucose levels
When does pancreatic polypeptide increase/
increases after meals and remains high for several hours
Which hormones does the stomach release?
- ghrelin: stimulates hunger and GH release
- gastrin: acid secretion
Which hormones does the pancrease secrete?
- insulin and glucagon: glucose homeostasis
- pancreatic polypeptide: gastric motility and satiation
- amylin: glucose homeostasis and gastric motility
What is ghrelin important for?
ghrelin is an important meal initiation signal
What is prader-willi syndrome caused by?
excessive ghrelin secretion - cannot stop eating and do not feel satiated
Where are GLP-1 made?
In L cells in the ileum and colon
How long is the half life of GLP-1?