Integration of Metabolism Flashcards
Postprandial hypoglycemia
exaggerated insulin release after meal
-cuz high glycemic index food
frequent small meals
Alcohol hypoglycemia
elevated NADH-makes gluconeogenesis and TCA slow down
insulin induced hypoglycemia trx
mild-give carbs orally
severe-adminster glucagon subcutaneously/intramuscularly
Pathways for liver @ starvation
degrades glycogen to produce glucose for export
-after deplted-does gluconeogenesis from AA, glycerol ,adn lactate
recieves FA from adipose tissues-oxidizes them to produce energy and ketone bodies for export
how does body recover for loss of liver glycogen
glocuoneogenic pathway in liver and kidenys
-glucose for brain and RBC
FA bbecome primary fuel
-large about of FFA to liver-high levels of acetyl Coa-TCA slows down and makes aceyl COA shift to ketogenesis to make ketone bodies
Brain pathways under starvation
Use glucose normally
now use ketone bodies to get acetyl coa to run TCA cycle
Beta ox-makes NADH and hydroxy butyrate (main ketone body)-leads to acetoacetate
DM criteria
Wait above 40 or 35 inches TAgs over 150 HDL less than 40, 50mg (woman) BP over 130/85 fasting glucose over 110
need 3
stims for glycogenolysis
stronger-epi/norepi
strong-glucagon
stims for glucogenesis
stim by glucagon and cortisol
DM metabolic tissue (in terms of insulin)
- subcat white adipose
- BAT
- visceral white
-insulin sensitive-can still store sugar
BAT-maks you more insulin sesntive
Visceral white-insulin resistant
adipokines
signalling proteins secreted by adipose tissue
intraabdominal adiposity results in
increase inflammatory marekrs, increased FFA, increased adipokines
-dyslipidemia, insulin resistance, inflammation
Role of visceral adipose tissue in insulin resistance
FFA to liver, adipose as secretory organ, excess fat influences insulin signalling/secretion
NEFA
nonesterified free FA-made by fat cells
inhibit inuslin secretion (turns off GLUT4)
-glucose taken up by muscle
more gluconeogenesis
Adipocytic hormones
- resistin
- leptin
- adiponectin
resistin-pro hyperglycemic
-inhibits AMPK-gluconeogenesis activated
letpin and adiponectin-reduce hyperglycemia
- if problems with receptor/secretion=hyperglycemia
- activate AMPK
these affect CNS (change if hungry/want to excercise=@ hypothalamus)
AMPK functions (6)
even in absence of glucose
- muscle glucose uptake
- muscle glycolysis
- beta ox
- decrease lipolysis in adipose tissue
- inhibit FA synthesis
- inhibit gluconeogenesis
DM and starvation
DM is starvation in presence of high blood sugar
CCK, GLP1, GIP
CCK-weaker than otehrs
bind to INCRETIN receptor
activate cAMP
- leas to secretion of insulin/ihibition of glucagon
- lwoers blood glucose
glucose independent insulin secretion
Why clinical consequences in organs without inuslin depence
if has insulin depence-glucose doesnt go in here
- if doesnt have it-glucose can build up here
- aldose reductase to make sorbitol
- H2o difuses in
chornic elevated glucose effects (2)
nonenzymatic glysoylation
-chagnes property of protein-reduces half life (but HbA1c lasts 120 days?)/enzymatic activity/binds to things should bind
aldose reductase
-results in
glocuse adn NADPH to sorbitol
neprhopathy, neuropathy, lens problems
DM 1 and autoimmune attack
Initating event-virus/toxin exposure starts B cell destruction
- starts slow and remains kinda slow
- see clinical disease only when 90% beta cells destroyed
DM2 and weight loss
will occur cuz cant take glucose into cells
Hyperglycemia Sx
3P
polyphagia, polyuria, polydipsia
3P mechs
polyphagia-increased lipolysis and protein catabolism
polyuria-hyperglycemia and ketoacidosis=effecive osmoles
Polydipsia-volume depletion
3 more bad thigns about DM
- hypertag-LPL low beucase less when insulin low
- ketoacidosis-increase FA mobilization from adipose, to liver beta ox-to syntehsis of ketone bodies
- overproduction of glucagon
Ketoacidosis and DM1 or 2
Most likely in DM1
Intensive vs standrard insulin therapy
Intensive therapy decrease HbA1C alot more than standard but its not good for small children since can result in hypoglyemia
DM2
milder sx than type 1
- usually no ketoacidosos
- HYPERTAG-VLDL production
- more LDL since have some insulon
- usually dont need insulin trx-unless let it get really bad lol
Adult onset DM2
gradual appearnce of insulin resistance
- often higher levels in begining but still no response of GLUT4
- highly genetic (DM1 not highly genetic)-polygenic
insulin trx in DM1 vs 2
DM1 has high decrase of glucose
DM2 has no decrease in glucose (cuz receptors dont work)
Insulin vs glucose
- normal
- DM 2
Blood glucose levels stay within narrow limitts
DM2 has to make alot more insulin to keep it wihin these narrow limits
why insulin makes less ketogenesis
less lipolysis (ratio of glucagon to insulin isnt that bad)
- increased LPL
- less VLDL but still elevated
glucose/FFA tox
changes activity of insulin and uptake of gluocse by muscle/adipose tissue
Alpha glucosidase inhibs
Acarbose
slow absorption of carbs-reduce postprandial elevationsin plasma glucose
sulfonylureas
gliuride
Cause depolarization of beta cell membrane-open Ca2+ channels-more Ca2+ into cell, stimulates insulin secretion
Metoformin
inhibits gluconeogenesis
Inhibits Oxphos Complex I
-males AMP level increase
—-blocks glucagon-R
———-leads to glycolytic and gluconeogenesis
—-AMPK activates
———-Improved insulin-R funciton, improved Glut4, less FA syn
DPP4 inhibitor
Januvia
DPP4 decreades incretins
-block this and have insulin secretion
SGLT2 inhibs
block glusoe reabosption in distal kidney (90% resorpbtion)
SGLT1 in stomach and prox kidney (10% resoption)
acute complicatns of DM1 vs 2
nutrtional status at disease onset
ketoacidosis-1, undernourished
2-hyperosmolar state, overnourished
