Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Gastrointestinal System > Metabolic Syndrome - Abali 3/17/16 > Flashcards

Metabolic Syndrome - Abali 3/17/16 Flashcards

1
Q

blood glucose levels and stress

A

stress

→ glucagon (alpha cells of pancreas), norepi/epi (adrenal medulla), cortisol (adrenal cortex)

→ spike in blood glucose via metab of carbs/lipids

effect on glycogenolysis…

+++ epi/norepi

++ glucagon

0 cortisol

effect on gluconeogenesis…

++ glucacon

++ cortisol

0 epi/norepi (will activate HSL to stim beta ox, but not gluconeo)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

types of hypoglycemia

A

insulin-induced hypoglycemia (diabetic patients)

  • mild tx* : oral carbs
  • severe tx* : admin glucagon subcutaneously/intramuscularly

post-prandial (exaggerated insulin release after meal)

tx : frequent small meals

fasting hypoglycemia

alcohol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

liver during starvation (overview)

A

glycogenolysis: glycogen → glucose for export

  • once glycogen stores depleted (~18 hr), gluconeogenesis kicks in through degradation of a.a.s, glycerol, lactate
    • once gluconeogenesis starts to target muscle breakdown of essential organs, it levels off and you shift to ketogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

liver metabolism in starvation

after first 24 hr

A

to make up for loss of liver glycogen…

  1. flux through gluconeogenic pathway increases → more glucose made for brain, RBCs
  2. FAs become primary fuel → saves glucose for brain, RBCs
  • as blood glucose levels off at low bound during extended starvation → FAs also used by liver for increased synth of ketone bodies for the brain
  • beta-hydroxybutyrate and aceto acetate can cross blood brain barrier→ acetyl CoA (in brain) → TCA cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

criteria for metabolic syndrome

A

1. central obesity : M > 40in, F > 35 in

2. fasting TAG : > 150mg/dl

3. low HDL : M < 40, F < 50

4. bp : > 135/85

5. fasting glucose : > 110

3 or more = metabolic syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

types of fat tissue and characteristics

A

1. brown adipose tissue used for thermogenesis and is insulin sensitive

2. subcutaneous white adipose tissue (hips) is insulin sensitive → able to store glucose

in contrast…

3. visceral white adipose tissue (abd) is insulin-resistant → gives you DM2, metabolic syndrome, risk for mortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

role of visceral fat in metabolic syndrome

A

visceral intra-abd fat does a lot of stuff that has overall effect of increased cardiometabolic risk

  • increase in FFAs
  • increase in adipokine secretion (and decrease in adiponectin - antihyperglycemic)
  • increase in inflammatory markers (C-reactive protein)

→ dyslipidemia, insulin resistance, inflammation

→ increased cardiometabolic risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

effects of NEFA (non-esterified FAs) on metabolism

A

adipose-derived non-esterified FAs…

  • pancreas: inhibits insulin secretion
    • muscle: decreases glucose uptake (GLUT4 regulated by insulin!)
    • fat cells: decreases glucose uptake (GLUT4 regulated by insulin!)
  • liver: stimulates gluconeogenesis

collectively, hyperglycemia → DM2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

***effects of adipocyte-secreted proteins on metabolism

A

prohyperglycemic/prodiabetic

  • resistin : inhibits AMPK signalling

antihyperglycemic/antidiabetic

  • leptin : activates AMPK signalling
  • adiponectin : activates AMPK signalling

AMPK signalling…

  • increased glucose uptake in muscle
  • increased glycolysis in muscle
  • increased beta ox
  • decreased lipolysis in adipose tissue
  • inhibited FA synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

normal vs obesity profiles of AMPK regulation

A

healthy individual

adiponectin and leptin : antihyperglycemic

  • activate AMPK pathway → catabolic pathways activated
  • glucose uptake by extrahepatic tissues → no hyperglycemia!

resistin : prohyperglycemic

  • inhibits AMPK pathway → synthetic pathways activated, gluconeogenesis activated
  • obese individual*

adiponectin and leptin : NONE or adiponectin/leptin insensitivity

  • AMPK pathway is not activated → catabolic pathways inhibited, glucose uptake by extrahepatic tissues inhibited

resistin : prohyperglycemic : high levels

  • inhibits AMPK pathway → synthetic pathways activated, gluconeogenesis activated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

leptin

A
  • antihyperglycemic effects on organs

also

  • interacts with CNS → alters signalling from hypothal to decrease food intake, increase energy expenditure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

3 types of diabetes mellitus

A

DM1 (5-10%) : formerly insulin-dependent diabetes/juvenile-onsetdiabetes

  • autoimmune destruction of pancreatic beta cells

DM2 (90-95%): formerly non-insulin dependent diabetes/adult-, maturity-onset diabetes

  • insulin resistance and/or beta cells making insufficient insulin

gestational diabetes: temp condition in some pregnancies (affects 4% of all preg women)

  • big babies, increases chances of baby growing up to have diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

mechanism of insulin secretion

A

beta cells in pancreas

  • glucose enters through GLUT2 transporter
  • glucose metabolized → ATP
  • increase in ATP → ATP-sensitive K channels close → intracellular K builds up → cell depolarizes
    • depol activates voltage-dependent Ca channels → increase in intracellular Ca → triggers secretion of insulin from secretory granules!

or

  • incretins bind to incretin receptor → activate cAMP pathway → triggers secretion of insulin from secretory granules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

incretins

A

GI hormones that lead to “anticipatory” rise in insulin in response to eating (before glucose levels actually become elevated and glucose → ATP can act on the K and Ca channels of pancreatic beta cells)

  • CCK (weak response)
  • GLP-1 (glucagon-like peptide)
  • GIP (gastric inhibitory peptide)

some DM2 drugs target hydrolases that degrade insulin → more incretins = more insulin → better response to insulin!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

long term consequences of untreated hyperglycemia

A
  • diabetic retinopathy: blindness
  • diabetic neuropathy: occlusive vasc disease/neuropathy → amputation
  • diabetic nephropathy
  • atherosclerosis, HTN, CVD (stroke, MI)

new level for diabetes diag is fasting glucose > 126 mg/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what organs does diabetes affect most?

WHY?

A

eyes, kidneys, nerves, heart/vessels

  • these organs do not have insulin-dep transporters
  • insulin insensitivity → glucose is not picked up by insulin-dep transporters on sk muscle/adipose tissue → stays in blood → accumulates in the tissues with insulin-indep transporters (like the ones above)
17
Q

effects/changes occuring due to chronic elevated glucose

A
  1. non-enzymatic glycosylation
  • glycation of Hb → elevated HbA1c, used to get an idea of longer-range glucose level
  • glycosylation of proteins can affect half-life, activity, binding
  1. stimulation of polyol pathway in specific tissues
    * glucose → sorbitol (kidneys, nerve, lens) [aldose reductase]
18
Q

Type 1 DM

A

autoimmune destruction of pancreatic beta cells → reduced capacity to secrete insulin

  • relatively modest genetic component

abrupt appearance of symptoms due to hyperglycemia

  • 3Ps: polyphagia, polydipsia, polyuria
  • weight loss despite constant hunger
19
Q

explanation for symptoms of DM1

  • symptoms of DM1
  • major diff between DM1, DM2
  • explanation of 3Ps
A
  • can’t pick glucose up from blood (sk muscle, adipose transporters; liver glucokinase are insulin-sensitive) → hyperglycemia and hyperuricemia
  • absence of insulin/overproduction of glucagon
    • glucagon stimulates gluconeogenesis → further elevates blood glucose
    • low insulin → low LPL synthesis → VLDL accumulation = hypertryglyceridemia
    • glucagon/epi stimulate HSL → mobilization of FA from adipose tissue, rise in hepatic beta ox, rise in ketogenesis → ketoacidosis

major diff between DM1 and DM2

  • much greater ketone body production in DM1

explaining the 3Ps

increase in glucose/ketones in blood → polyuria

increased lipolysis/protein degradation → polyphagia

volume depletion → polydipsia

20
Q

tradeoff between standard and intensive insulin therapy

A

intensive has better control of blood sugar, lower HbA1c but 3x likelihood of hypoglycemia

  • can treat with glucose (mild) or glucagon (severe)

intensive not appropriate for children and elderly

  • brain devpt in children
  • stroke/MI in elderly
21
Q

Type 2 DM

  • symptoms, onset, genetics
  • specific symptoms
  • distinguishing symptom
  • tx
A

milder symptoms than DM1, more gradual onset, prob a greater genetic component

  • hyperglycemia without ketoacidosis
  • less triglyceridemia (SOME insulin → more LPL action → better processing of VLDL, so less buildup)

LINK BETWEEN INSULIN RESISTANCE AND OBESITY! (VISC FAT)

  • desensitization of insulin receptor signaling → insulin tx prob wont give you a correction of symptoms

tx: diet/weight loss (insulin rare)

22
Q

how does obesity → insulin resistance

how does insulin resistance → hyperglycemia?

A

obesity via more visceral fat → increase in resistin; decrease in adiponectin, leptin secreted → insulin resistance

  • adipose tissue: less beta ox, more lipolysis → elevated FFA
  • liver: more gluconeogen → hyperglycemia
  • extrahep insulin-sensitive tissues: lower glucose uptake → hyperglycemia
23
Q

why is ketosis minimal in DM2?

A

insulin downregulates hepatic ketogenesis (even in case of insulin-resistance)

24
Q

treatment of DM2

A
  • diet
  • weight reduction
  • exercise
  • drugs (sulfonylureas, etc)
  • insulin (maybe 1/3 of DM2 pts)
25
Q

acarbose

A

inhibition of alpha-glucosidases (breakdown of starch, sucrose)

  • slows absorption of carbs → reduces postprandial elevation in glucose
26
Q

sulfonylureas (gliburide)

A

binds to ATP-sensitive K channel → longer depol/Ca/secretory vesicle action → more insulin secreted into circ

  • insulin secretagogue
  • reduction of serum glucagon
  • augmentation of insulin signaling
27
Q

biguanides (metformin)

A

current understanding: acts by inhibiting oxphos Complex I → ATP production lower, AMPK production higher

  • higher AMP → less phosphorylation of adenylate cyclase by glucagon → lower cAMP → lower PKA signalling → less gluconeogen, more glycolysis

inhibition of gluconeogenesis

28
Q

DPP4 inhibitors (Januvia)

A

inhibits hydrolase that degrades incretins → more incretins → stimulate beta cell insulin secretion

29
Q

SGLT2 inhibitors

A

reduce reabs of glucose by kidneys (more excretion)

  • increased risk of UTIs because more glucose in urinary tract = nutrition for bacteria
30
Q

thiazolidinedione (Avandia)

A

activates PPARgamma → increases insulin sensitivity of adipose tissue

31
Q

comparison of DM1 and DM2

A

Gastrointestinal System (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions