GLP-1 is inactivated by Dipeptidyl peptidase-4 (DPP4) in blood
GLP-1 agonist are a type of therapy used to prolong GLP-1stability and improve its rapid degradation by DPP4.
Insulin signaling in the hypothalamus INHIBITS AMPK function and signals a FED state in the brain
the [Insulin] INCREASES in the blood right after a meal
the oral glucose tolerance test measures a person's ability to clear excess glucose from the circulation
The [glucagon] in the blood DECREASES after a meal
HbA1c measures the level of hemoglobin glycosylation of the HB beta chain N-terminal Val residue
Metformin, Sitagliptin, Ozempic are used to treat type 2 diabetes.
HIGH GLUCOSE :
INSULIN stimulates glucose uptake, glycogen synthesis, and FA synthesis, uptake and storage
LOW GLUCOSE:
GLUCAGON stimulates glycogenolysis, gluconeogenesis, lipolysis, ketone body production
LOW GLUCOSE:
GLUCAGON stimulates glycogen mobilization, gluconeogenesis, glucose released into blood and FA mobilization
PKA - protein kinase A - activated through GLUCAGON cascade - DEACTIVATES ACC (FA metabolism)/HMGR (cholesterol) with addition of phosphate group (uses ATP) - inactivates glycogen syntahse
PP2A - priteins phosphatase 2A - activated through INSULIN cascade - ACTIVATES ACC (FA) / HMGR (cholesterol) with the REMOVAL of a phosphate group. Activates to make Malonyl-CoA (FA) to Mevalonate (Cholesterol).
PP1 - protein phosphate 1 - activated through INSULIN cascade - INACTIVATES phosphorylase and CLEAVES a phosphate group
LIVER -
GLUCAGON promotes glycogen breakdown, gluconeogenesis, and glucose export
promotes beta-oxidation and KB synthesis
ADIPOSE TISSUE:
GLUCAGON promotes mobilization of FA so glucose is reserved for use by the brain
PANCREAS:
GLUCAGON primarily targets Hepatic and Adipose tissues to signal the fasted state. Mobilizes fuels to spare glucose for the brain
EPINEPHRINE increases heart rate, blood pressure, dilation of respiratory pathways
LEPTIN inhibits AMPK - stopping food intake
Ghrelin/Adiponectin signals to hypothalamus from AMPK of hunger
glucose levels decrease w prolonged starvation
ketone bodies greatly increase with further starvation
phase 1 of starvation : GLYCOGENOLYTIC phase
only liver exports glucose
liver glycogen is rapidly depleted within 16-24h
phase TWO of starvation : GLUCONEOGENIC phase
glycogen all depleted
only source of glucose bc FAs are unusable at this point
FAs cant be used to make glucose
FAs cant be used by the brain
ONLY SOURCE OF GLUCOSE IS --> GLUCONEOGENSIS
HOWEVER, proteins are being degraded TOO FAST
UNSUSTAINABLE
would only last 20-30 days
starts the shift to phase 3 - where the brain shifts to using KBs as fuel
phase THREE of starvation : KETOGENETIC phase
rate of FA mobilization reaches its PEAK
KB production in liver increases
brain adapts to use ketone bodies
REDUCED GLUCOSE CONSUMPTION
REDUCED AMINO ACID BREAKDOWN
LAST RESORT FOR SURVIVAL
phase FOUR of starvation : TERMINAL phase
run out of fat
start degrading massive amounts of protein
DEATH - no more sources of incoming metabolism
Starvation in the midst of plenty - excess glucose not taken up, the body keeps telling you that you're still starved even when you eat
Diabetes Mellitus - a lack of insulin function
glucose is not absorbed by tissues or reabsorbed by kidneys
glucose is excreted taking lots of H2O with it
urination is excessive, excess thirst
urine is sweet
Oral glucose tolerance test - measures blood glucose before and every 30 mins after
Hb-A1c test - measures the percent of hemoglobin that has been glycated with the open structure of glucose
higher percentage = more glucose being attached to hemoglobin
TYPE ONE DIABETES
lack of pancreatic beta cells
NO PRODUCTION OF INSULIN
mern
cause - autoimmune disease that attacks pancreatic beta cells
responds to insulin injectionsan
TYPE TWO DIABETES
non-insulin dependent diabetes mellitus
body becomes RESISTANT to insulin
insulin is present but doesn't produce the normal signals
consequences of diabetes :
DAMAGE TO NERVES / BLOOD VESSELS : neuropathy, kidney disease, eye disease, risk of heart disease
gum disease and tooth decay
ketoacidosis - excess FA mobilized and excess KB produced (NOT GOOD)
metformin - drug that inhibits gluconeogenesis in the LIVER and increases glucose uptake by muscle to combat type TWO diabetes