Glucose Regulation Flashcards
Where are glucagon receptors mainly expressed?
- in liver and kidney
Which cell types have insulin receptors (that are focused on for this course)?
- liver, muscle and adipose
- plus insulin regulates self in pancreas
How is blood glucose under control? Why is it controlled?
- under extremely tight control
- because glucose main energy source for cells to use
How does insulin and how does glucagon affect blood glucose?
- insulin decreases blood glucose
- glucagon increases blood glucose
When do pancreatic hormones work together?
- to regulate blood glucose after meals and in between meals
What hormones are from the pancreatic islets? What are the other two important blood glucose regulation hormones?
- insulin, glucagon, somatostatin
- glucagon-like peptide-I and gastric inhibitory peptide (aka glucose-dependent insulinotropic peptide)
What are glucagon-like peptide-I and gastric inhibitory peptide? What is their function?
- both incretins
- proteins that amplify insulin effects and are secreted by cells of the small intestine
What cells does the pancreas contain?
- islets of langerhans
- B cells: insulin (center)
- A cells: glucagon (periphery)
- D cells: somatostatin (periphery)
How is insulin involved in paracrine feedback?
- activates beta cells (insulin producers) and inhibits alpha cells (glucagon producers)
How is glucagon involved in paracrine feedback?
- activates alpha cells, activates beta cells, activates delta cells
How is somatostatin involved in paracrine feedback?
- inhibits alpha cells, inhibits beta cells
Where is GLP-I made and why is this interesting?
- made in intestine
- same precursor as glucagon but very different function!
How is GLP-I involved in paracrine feedback?
- acts on pancreas as potent stimulator insulin transcription and release after meals
- decreases secretion glucagon
- acts on other tissues as well as pancreas
How is GIP involved in paracrine feedback?
- amplifies insulin effects
- secreted by cells of the small intestine
What is hypoglycemia? What are the symptoms?
- if blood suar levels drop too low
- potentially fatal
- loss of consciousness, brain damage, lethal coma
What is hyperglycemia? What are the symptoms?
- short term: appetite suppressed
- long-term: chronic health problems associated with diabetes mellitus (eye, kidney, heat disease, nerve damage)
What is diabetes mellitus? What are the two types?
- deficiency in secretion or action of insulin
- Type I: no insulin
- Type II: insulin resistant
How is type I diabetes mellitus treated?
- used to use pork and beef but more expensive and unsafe
- now human insulin made in host bacteria factory
Cell surface receptors control gene expression by which pathways?
- MAPK, PKC, PI3K
How does phosphorylation occur and what does it result in?
- occurs in a chain reaction
- activates transcription factors that bind DNA and activate or repress transcription of genes into proteins
What pathways stimulate insulin secretion?
- calcium at voltage-gated calcium channel (VGCC)
- GLP-1 acting on GPCR
What pathway stumulates insulin synthesis?
- insulin at redeptor tyrosine kinase plus glucose sensor that transports glucose into cell
How long does it take to synthesize insulin?
- takes >1hr
- insulin stored for immediate release in response to food
What is required to release insulin?
- calcium (from mitochondria and voltage gated calcium channel stimulated by glucose)
What is required to link blood glucose levels to insulin secretion?
- glucose “sensor” mechanism
- metabolic coupling to potassium channels to control plasma membrane potential
- voltage dependent calcium channels
Where are insulin containing granules found?
- reserve pool and a readily released pool
What factors mediate insulin release?
- aa from food
- glucose from food
- incretins: proteins that amplify insulin effects (GLP-1 and GIP)
After release how long does insulin last? How is it removed from circulation?
- 3-5 minutes
- degraded by insulinases in liver, kidney, placenta
What are the steps in insulin release from B cell?
- glucose from meal
- a) increase ATP, cAMP/PKA signalling blocks K+ channel (cell depolarized)
- b) GIP and GLP-I act to increase cAMP/PKA (potentiates other steps)
- voltage sensitive calcium channel opens, influx
- increase calcium and increase in cAMP/PKA causes insulin release
- increase of calcium opens K-Ca channel that repolarizes the cell
What are growth factor receptors also known as?
- tyrosine kinase receptors
What is IGF-I?
- major player in GH axis
- produced in liver
- negative feedback on GH
- protein synthesis and cell proliferation
- insulin family and same receptor type
What is IGF-II?
- fetal growth hormone
- in liver
- mediates GH effects
- insulin family too
What is insulin implicates for?
- implicated for carb metabolism
- implicated for fetal growth
What kind of receptor does insulin use?
- growth factor receptor dimer (made with S-S bridges)
- enzyme tyrosine kinase is a part of receptor
- binds extracellularly
What does insulin binding result in?
- adds phosphate to substrates that recruit other proteins (signaling complexes)
- adds phosphate to proteins that also kinases (phosphorylation cascades)
What do we share our hormone ancestry with?
- sea squirts!
- insulin and IGF
How do genes evolve through gene duplication?
- gene doubles
- can than mutate one gene to acquire new function without messing up the organism
- IGF-1 to IGF-II
What are GLUTs?
- important for transporting glucose into the cell
- different ones on membranes of different cell types in different tissues
What are some of insulins effects?
- metabolic storage hormone
- increase cell growth
- critical for fetal growth
- directly suppresses glucagon transcription
What does insulin store as a metabolic storage hormone?
- glycogen to store glucose
- triglyceride to store fat
- protein synthesis to store amino acids
How does insulin increase cell growth?
- via growth factor receptor (tyrosine kinase receptor)
How does insulin suppress glucagon transcription?
- glucagon gene has an insulin response element
What are the two pathways following growth factor receptor with tyrosine kinase?
- mitogenic (growth via MAPK)
- metabolic (store food after a meal via PI3K/PKB) (also known as Akt pathway)
What are the effects of the PI3K/PKB pathway on the liver?
- decrease gluconeogenesis
- increase glyogenesis
- decrease glycogenolysis
What are the effects of the PI3K/PKB pathway on the muscle?
- increase glucose transport
- increase glycogenesis
- increase protein synthesis
What are the effects of the PI3K/PKB pathway on the pancreas?
- increase b-cell growth
- increase insulin secretion
What are the effects of the PI3K/PKB pathway on the adipocytes?
- increase glucose transport
- increase protein synthesis
- increase lipogenesis
- decrease lipolysis
How are insulin receptors downregulated?
- receptor desensitized by internalization once insulin bound - endosomes to lysosomes, acidification and degraded
- downregulated if chronic insulin
