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Metabolic Basis of Disease > Insulin and Glucose Homeostasis > Flashcards

Insulin and Glucose Homeostasis Flashcards

1
Q

Defense against hypoglycemia (4 steps)

A
  1. 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
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2
Q

where gluconeogenesis occurs

A

liver and kidneys

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3
Q

C peptide

A

co-secreted with insulin and useful measure of insulin secretion because it is cleared more slowly (helps differentiate between endogenous and exogenous insulin)

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4
Q

IAPP

A

islet amyloid polypeptide (amylin) - co-secreted with insulin and component of amyloid fibrils that kill beta cells

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5
Q

GLUT2

A

transporter that allows glucose to enter beta cells and liver cells - low affinity, high capacity transporter

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6
Q

UCP1

A

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

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7
Q

SGLT1

A

Sodium coupled active transporter for glucose uptake in intestine

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8
Q

SGLT2

A

Sodium coupled active transport in kidneys- prevents urinary excretion of glucose

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9
Q

GLUT1

A

Very efficient glucose transporter (facilitated diffusion) found in brain

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10
Q

GLUT4

A

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)

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11
Q

Insulin promotes triglyceride storage (4 ways)

A

By 1) increasing lipoprotein lipolysis; 2) increasing FFA uptake; 3) inhibiting hormone-sensitive lipase; 4) increased lipogenesis - minor effect

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12
Q

Effect of insulin on lipids in diabetic patients

A

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

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13
Q

SIRT1

A

downregulates UCP1 so it increases amount of ATP produced per same amount of glucose - increases insulin secretion, SIRT1 also promotes FOX01

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14
Q

functions of insulin

A

Insulin suppresses release of glucose from the liver and enhances uptake in skeletal muscle. Insulin helps regulate metabolism and growth

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15
Q

MODY

A

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)

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16
Q

IRS1

A

insulin receptor substrate 1 - transmits signals from insulin receptor and insulin-like growth factor (IGF) receptor to the PI3K/Akt pathway

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17
Q

PI3K

A

kinase that binds to IRS1 and activates PKB/Akt

18
Q

Akt/PKB

A

kinase important for insulin signaling –> phosphorylating GSK3 to disinhibit glycogen synthase and recruiting GLUT4 to the membrane

19
Q

what occurs when glucose enters beta cell

A

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

20
Q

Leptin

A

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

21
Q

Lipodystrophy

A

Causes severe insulin resistance in skeletal muscle and liver; fatty acids that should be in adipose tissue are in liver

22
Q

Sulphonyl urea

A

Shuts down K channels which induces depolarization in beta cells, leads to insulin secretion

23
Q

Central diabetes insipidus

A

polyuria occurring because pituitary gland does not make enough ADH

24
Q

Type 1 diabetes

A

autoimmune destruction of beta cells so insulin is not produced; major susceptibility gene located in HLA region on chromosome 6

25
Q

GLP-1

A

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

26
Q

DPP4 inhibitor

A

drug for diabetes that increases the concentration of bioactive GLP-1 by inhibiting degradation of GLP-1

27
Q

metformin

A

insulin sensitizer drug, activates AMPK

28
Q

fibrates

A

drug for diabetes that increases fatty acid uptake and oxidation in liver and muscle - ligand of PPARa

29
Q

TZDs

A

drug that causes fat redistribution (visceral to subcutaneous) and improves insulin sensitivity - agonist of PPARgamma

30
Q

Statin

A

reduces endogenous production of cholesterol by inhibiting HMG CoA reductase

31
Q

Rimonabant

A

drug that suppresses appetite (inhibits CB1)

32
Q

NPY

A

neuropeptide Y is produced in the ARC under fasting conditions and causes increased food intake (orexigenic)

33
Q

AgRP

A

(agouti related protein) produced in ARC under fasting and targets MC4 receptor and results in increased food intake (orexigenic)

34
Q

Reward system

A

palatable food causes opioids, dopamine, endocannibinoids etc that make us feel happy to eat

35
Q

CART

A

anorexic signal produced in ARC that blocks NPY signaling and results in decreased food intake (stimulated by cocaine and amphetamines)

36
Q

alphaMSH

A

Produced under feeding in ARC which binds MC4 receptor and counteracts AgRP (decreased food intake, anorexic signal)

37
Q

Ghrelin

A

Produced in stomach upon fasting - signals us to eat (orexigenic)

38
Q

POMC

A

signals satiety/decreases appetite (related to alphaMSH)

39
Q

FOX01

A

transcription factor that helps regulate glucose metabolism by promoting gluconeogenesis

40
Q

G6Pase

A

helps with gluconeogenesis, increased by FOX01

41
Q

PEPCK

A

helps with gluconeogenesis, transcription increased by FOX01

42
Q

CREB and CRTC2

A

both needed for gluconeogenesis

Metabolic Basis of Disease (3 decks)

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