Insulin and Glucose Homeostasis Flashcards
Defense against hypoglycemia (4 steps)
- insulin levels decline 2. glucagon stimulates glycogenolysis 3. adr. epinephrine stimulates glycogenolysis/gluconeogenesis (when glucagon is deficient) 4. cortisol and growth hormone support glucose production & limit glucose utilization
where gluconeogenesis occurs
liver and kidneys
C peptide
co-secreted with insulin and useful measure of insulin secretion because it is cleared more slowly (helps differentiate between endogenous and exogenous insulin)
IAPP
islet amyloid polypeptide (amylin) - co-secreted with insulin and component of amyloid fibrils that kill beta cells
GLUT2
transporter that allows glucose to enter beta cells and liver cells - low affinity, high capacity transporter
UCP1
uncoupling protein regulates mitochondrial membrane -high levels mean you get less ATP from same amount of glucose, less ATP means less insulin released, UCP1 turns energy from fatty acids into heat rather than ATP in brown adipose tissue
SGLT1
Sodium coupled active transporter for glucose uptake in intestine
SGLT2
Sodium coupled active transport in kidneys- prevents urinary excretion of glucose
GLUT1
Very efficient glucose transporter (facilitated diffusion) found in brain
GLUT4
insulin-sensitive glucose transporter that brings glucose into adipocytes and muscle (when glucose levels are high and only when insulin is present - otherwise transporter is pulled inside cell) (facilitated diffusion)
Insulin promotes triglyceride storage (4 ways)
By 1) increasing lipoprotein lipolysis; 2) increasing FFA uptake; 3) inhibiting hormone-sensitive lipase; 4) increased lipogenesis - minor effect
Effect of insulin on lipids in diabetic patients
insulin fails to suppress FFA release from adipocytes, excess FFAs are taken up by the liver, acetyl CoA fails to enter TCA cycle so converted to ketones –> ketosis is indicator of insulin concentration
SIRT1
downregulates UCP1 so it increases amount of ATP produced per same amount of glucose - increases insulin secretion, SIRT1 also promotes FOX01
functions of insulin
Insulin suppresses release of glucose from the liver and enhances uptake in skeletal muscle. Insulin helps regulate metabolism and growth
MODY
Maturity onset diabetes in the young - results from a mutation in a single gene (either transcription factor related to beta cells or decreased ability to form beta cells)
IRS1
insulin receptor substrate 1 - transmits signals from insulin receptor and insulin-like growth factor (IGF) receptor to the PI3K/Akt pathway
PI3K
kinase that binds to IRS1 and activates PKB/Akt
Akt/PKB
kinase important for insulin signaling –> phosphorylating GSK3 to disinhibit glycogen synthase and recruiting GLUT4 to the membrane
what occurs when glucose enters beta cell
glucose enters through GLUT2 transporter; the ATP produced then triggers the ATP-sensitive K+ channel to close which causes depolarization which opens Ca+2 channel… increased Ca+2 causes more fusion of insulin vesicles with the membrane –> insulin secreted from cell
Leptin
anti-hyperglycemic hormone/sensitizing toward insulin, signals feelings of satiety (anorexic signal - decrease food intake) and has anti-diabetogenic effects - produced by white adipose tissue
Lipodystrophy
Causes severe insulin resistance in skeletal muscle and liver; fatty acids that should be in adipose tissue are in liver
Sulphonyl urea
Shuts down K channels which induces depolarization in beta cells, leads to insulin secretion
Central diabetes insipidus
polyuria occurring because pituitary gland does not make enough ADH
Type 1 diabetes
autoimmune destruction of beta cells so insulin is not produced; major susceptibility gene located in HLA region on chromosome 6
GLP-1
Senses carbohydrates in intestine, signals us to stop eating (anorexic - decreases food intake) also drug for treating diabetes, it stimulates insulin release and acts via the GLP-1 receptor in the brain or pancreas
DPP4 inhibitor
drug for diabetes that increases the concentration of bioactive GLP-1 by inhibiting degradation of GLP-1
metformin
insulin sensitizer drug, activates AMPK
fibrates
drug for diabetes that increases fatty acid uptake and oxidation in liver and muscle - ligand of PPARa
TZDs
drug that causes fat redistribution (visceral to subcutaneous) and improves insulin sensitivity - agonist of PPARgamma
Statin
reduces endogenous production of cholesterol by inhibiting HMG CoA reductase
Rimonabant
drug that suppresses appetite (inhibits CB1)
NPY
neuropeptide Y is produced in the ARC under fasting conditions and causes increased food intake (orexigenic)
AgRP
(agouti related protein) produced in ARC under fasting and targets MC4 receptor and results in increased food intake (orexigenic)
Reward system
palatable food causes opioids, dopamine, endocannibinoids etc that make us feel happy to eat
CART
anorexic signal produced in ARC that blocks NPY signaling and results in decreased food intake (stimulated by cocaine and amphetamines)
alphaMSH
Produced under feeding in ARC which binds MC4 receptor and counteracts AgRP (decreased food intake, anorexic signal)
Ghrelin
Produced in stomach upon fasting - signals us to eat (orexigenic)
POMC
signals satiety/decreases appetite (related to alphaMSH)
FOX01
transcription factor that helps regulate glucose metabolism by promoting gluconeogenesis
G6Pase
helps with gluconeogenesis, increased by FOX01
PEPCK
helps with gluconeogenesis, transcription increased by FOX01
CREB and CRTC2
both needed for gluconeogenesis
