Week 4 Hormones Affecting Glucose Metabolism Module Flashcards
T2DM is characterized by…
hyperglycemia
what is the underlying pathophysiology of T2DM (5)
peripheral insulin resistance, progressive B-cell dysfunction, hypersecretion of glucagon, accelerated gastric emptying (increased postprandial glucose levels), impaired incretin effect
what is the role of incretins? where are they located?
gut peptides that stimulate insulin secretion following oral nutrient ingestion or postprandially. A large proportion of the insulin response in healthy individuals in incretin-mediated (IV glucose infusions do not create the same amount of insulin as equivalent oral glucose intake)
following a meal compare insulin and glucagon level in a normal and T2DM individual
Normal: insulin levels rise, glucagon levels
T2DM: delayed and suppressed insulin response, glucagon over-secretion
what are the two major type of incretins in humans?
GLP-1 and GIP
GLP-1 secreted by? location?
Gut-L cells (eneteroendocrine cells) located in distal ileum and colon. (GLP-1 is derived form the transcription product of proglucagon gene)
describe GLP-1 release into circulation
Biphasic: release shortle after food ingestion and then another as food interacts with L-cells in ileum and colon
what is the role of GLP-1 on the pancreas 2
potentiates insulin release from B cells, inhibits glucagon secretion
what is the role of GLP-1 outside of the pancreas 4, and one long-term
inhibits gastric emptying (slows rate of nutrient absorption and slows rate of glucose appearing in the blood)
reduces appetite,
enhances insulin sensitivity of peripheral tissues (skeletal muscle)
cardioproteciton and neuroprotection
long term: increase B-cell mass
GIP; where is it produced, by what cell type?
produced in duodenum and jejunum by K cells
GLP-1 and GIP are secreted in response to….and are degraded within minutes by
ingestion of food, dipeptidyl peptidase-4 (DPP4)
contrast role of GLP-1 and GIP
both stimulate insulin secretion and expand B cell mass. Only GLP-1 suppresses glucagon, inhibits gastric emptying, and decreases food intake
compare GLP-1 and GIP secretion in T2DM
GLP-1 level is decreased, GIP levels typically not decreased
is GLP-1 replacement effective in reducing Fasting Plasma Glucose in T2DM?
Yes! increases insulin, decreased glucagon
is GIP replacement in reducing FPG in T2DM?
no, GIP levels are normal in T2DM yet functionally ineffective in stimulating insulin secretion
what is one obstacle in using GLP-1 as a therapy? what are 2 potential solutions?
it is degraded relatively quickly by DPP-4 located in human serum. Solution: create a GLP-1 mimic that can bind pancreas but not be degraded by DPP-4, or by inhibiting DPP-4
what is Exenatide (Byetta), method of taking?
GLP-1 receptor agonist, mimics the effects of GLP-1 (twice daily injection treatment)
what is Liraglutide? method of taking?
modified synthetic peptide form human GLP-1 w/ a half life of 10-14hrs (once daily injection treatment)
What is DPP4i (vildaglipton and Sdaglipitn)? method of taking?
inhibitor of DPP-4 (prevent GLP-1 degradaiton), once daily ingestion
what are some pros/cons of DPP4 inhibitors and incretin mimitics?
DPP4I: ingestible (Pro), weight neutral (Pro)
GIP-1 analogs: SQ injected (con), increase risk of thyroid cancer (con), weight loss (pro)
what are counterregulatory hormones (CRH)?
CRH are hormones that work against action of insulin
ex of CRH 4? fast acting or slow
Glucagon (fast), Epinephrine (fast), cortisol (slow), growth hormone (slow)
elevations in CRH cause (5)
hepatic ketogenesis, increased lipolysis in adipose, increased proteolysis in muscle, increased glycogenolysis, increased gluconeogenesis
what is our bodies normal defense against hypoglycemia? (5)
insulin decrease, glucagon incresases, epinephrine increases, cortisol and growth hormones incease
defective defense against hypoglycemia is seen in…
T1DM
describe the impaired CRH response in hypoglycemia
glucagon response is lost and Epinephrine becomes main CRH against hypoglycemia. However, Epi response decreases after recurring hypoglycemia
What is hypoglycemia-associated autonomic failure
hypoglycemia induces further hypoglycemia by blunting the effects of epinephrine
what is diabetic ketoacidosis (DKA)? characterized by?
complication of diabetes where the body produces excess blood acids.
Characterized by hyperglycemia and ketonemia
what is the mechanism of DKA?
- Glucose is not utilized by the body (insuficient or absent insulin)
- The body begins to break down fat (for energy) resulting in ketone by-products that accumulate in the blood
- the accumulation of ketone and glucose are removed by the kidneys, but require more water do so
- water and excess glucose and ketones are lost but loss of water worsens ketoacidosis
what are symptoms of DKA (4)
nausea/vomiting
thirst (polyuria)
abdominal pain
shortness of breath
physical findings of DKA (5)
tachycardia, dehydration/hypotension, respiratory distress, abdominal tenderness, possibly coma
DKA is characteristic of ____ but a _____ can trigger it in _____
T1DM, severe illness, T2DM
what is hypoglycemia unawareness?
the fact that brain cells have a greater glucose uptake than other tissues leads to hypoglycemia unawareness
What would you expect so see in a T1DM patient who is suffering from his first hypoglycemia
suppressed glucagon and elevated epinephrine. For T1DM>5yrs, their glucagon response to hypoglycemia is lost and Epinephrine constitutes the main defense against hypoglycemia
