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Block 10 Week 2 > Duan > Insulin & Oral hypoglycemics (RED TEXT ONLY) > Flashcards

Duan > Insulin & Oral hypoglycemics (RED TEXT ONLY) Flashcards

1
Q

what does the maintenance of glucose homeostasis involve?

A

integration of several major organs via multilayered inter-organ communication

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2
Q

where does insulin come from?

A

pancreatic beta cells

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3
Q

what is central to the glucose homeostasis process?

A

adjustment of the amt of insulin that comes from beta cells

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4
Q

where does glucagon come from?

A

alpha cells

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5
Q

where does insulin come from?

A

beta cells

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6
Q

how are basal levels of circulating insulin maintained (post-absorptive)?

A

constant beta cell secretion

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7
Q

what happens w/ insulin after you eat a meal?

A

a burst/bolus of insulin secretion occurs in response to inc glucose & AAs

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8
Q

when is glucagon released?

A

when blood sugar is low

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9
Q

what does glucagon do?

A

releases glucose from tissues back into blood

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10
Q

where is insulin synthesized?

A

beta cells

as PROINSULIN

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11
Q

HOW is insulin formed?

A

proinsulin > proteolysis > insulin + C-peptide + 4 AAs

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12
Q

what is the structure of insulin?

A

A chain + B chain

joined by 2 interchain disulfide bonds

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13
Q

which chain of insulin has an interchain bond?

A

A chain

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14
Q

what are the 3 possible forms of insulin?

A

monomer
dimer
hexamer coordinated by 2 Zn atoms

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15
Q

what is the biologically active form of insulin?

A

monomer

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16
Q

what is the standard insulin preparation?

A

human insulin prep (Humulin) made as the recombinant protein

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17
Q

which has a greater capacity to stimulate insulin secretion: oral glucose or IV glucose?

A

ORAL!

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18
Q

what 3 components of food stimulate insulin secretion?

A

glucose
amino acids (arg, lys)
FAs & ketones

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19
Q

what regulates insulin release (think autonomic mechanisms)

A

Hypothalamus
Ventrolateral (vagus)
Ventromedial (sympathetic)

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20
Q

how does vagal/parasympathetic stimulation impact insulin release?

A

activates M receptors > INC insulin release

para is rest & digest

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21
Q

how does sympathetic stimulation impact insulin release?

A

activates alpha-receptors > DEC insulin release
however
beta 2 activation INC insulin release

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22
Q

how do insulin and glucagon interact?

A

Glucagon stimulates insulin secretion

Insulin inhibits glucagon secretion

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23
Q

how is glucose transferred into beta cells in humans?

A

GLUT1

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24
Q

what is the RLS in glucose metabolism in the beta cell?

A

glucose phosphorylation by glucokinase

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25
Q

what process leads to insulin release from beta cells (kinda long sorry)

A

INC ATP > inhibit ATP-sensitive K channel > depol > Ca influx > storage granule fusion > exocytosis of insulin + C-peptide

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26
Q

what 2 other factors (plus a mediator) can stimulate insulin release (besides food)

A

NTs (ACh)
Hormones (glucagon-like peptide 1 & incretins)
Glucose ENHANCES these

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27
Q

what is the fate of insulin?

A

insulin-receptor complex internalization > proteolysis by thiol metalloproteinase hydrolysis of the di-S linkage btwn A & B chains > receptor returns to cell surface

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28
Q

which cells degrade insulin?

A

tubular epithelial cells (kidney)

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29
Q

what are the principle targeting tissues for insulin regulation of glucose?

A

liver
muscle
fat

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30
Q

what does insulin STIMULATE (which processes)?

A

utilization & storage of glucose, AAs, & FAs

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31
Q

what does insulin INHIBIT (which processes)?

A

breakdown of glycogen, protein, & fat

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32
Q

what controls glucose metabolism?

A

increasing glucokinase activity, stimulating glycogen synthase, & inhibiting glycogen phosphorylase

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33
Q

generally, what is DM1?

A

lack of fxnal beta cells

either autoimmune or not

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34
Q

generally, what is DM2?

A

inadequate insulin response (normal insulin levels but ineffective > insulin resistance)

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35
Q

go thru Dr. Usera’s flash cards for the pancreas to learn about DM1 & DM2 & their sx & presentations

A

okie dokie

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36
Q

what meds pose a risk of hypoglycemia in diabetic pts & can cause secondary DM?

A

beta blockers

COLT DO NOT GET DIABETES

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37
Q

what are the 3 lifestyle changes you can implement to treat DM?

A

inc physical activity
appropriate diet
body weigh optimization

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38
Q

what 2 general classes of meds can you give for DM?

A
  1. insulin

2. hypoglycemics (oral or non-insulin injectables)

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39
Q

what are incretins?

A

hormones that the gut releases thruout the day; increase when you eat

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40
Q

what are the 2 major incretins?

A

GIP > glucose-dependent insulinotropic peptide

GLP-1 > glucagon-like peptide 1

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41
Q

what do incretins do?

A

facilitate the response of the pancreas & liver to glucose fluctuations via acting on pancreatic alpha & beta cells

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42
Q

what happens to incretins in DM2?

A

the incretin effect is diminished

  1. GLP-1 release is defective > GLP-1 levels are low
  2. insulinotropic response to GIP is diminished (not absent)
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43
Q

TO THE DRUG TABLES

A

LET’S GO

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44
Q

what is normal fasting blood glucose?

A

70-99

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45
Q

what is normal blood glucose two hours after a meal?

A

<140

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46
Q

t/f: insulin is stored in beta cells

A

true

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47
Q

constant b-cell secretion maintains low basal levels of circulating insulin during what period of time?

A

post-absorptive, aka between meals

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48
Q

basal insulin secretion suppresses what three processess?

A

lipolysis
proteolysis
glycogenolysis

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49
Q

Insulin is released in a bolus after ingestion of glucose or….

A

amino acids

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50
Q

Proteolysis of insulin results in three components?

A

insulin, C peptide, and four basic amino acids

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51
Q

What atom links the polymers of insulin?

A

Zn

52
Q

t/f: orally ingested glucose results in greater insulin stimulation than intravenous stimulation

A

true

53
Q

Gastrin, CCK, and GIP augment (blank) secretion

A

insulin

54
Q

What axis is responsible for digestion, absorption and regulation of utilization of foods?

A

enteropancreatic

55
Q

Which two particular amino acids stimulate insulin secretion?

A

Arginine and lysine

56
Q

What are the four molecules that can stimulate insulin secretion?

A
  1. glucose
  2. AA’s (Arg, Lys)
  3. FA
  4. ketone bodies
57
Q

Which vagal system regulates autonomic release of insulin?

A

ventrolateral system

58
Q

Which two sympathetic systems regulate autonomic release of insulin?

A

ventromedial and hypothalamic

59
Q

Vagal (aka parsymp) stimulation or cholinomimetic drugs increase insulin release through what receptor?

A

M receptor

60
Q

Exercise, hypoxia, hypothermia, trauma, or burns does what to insulin secretion?

A

inhibits it

61
Q

sympathetic stim (Exercise, hypoxia, hypothermia, trauma, or burns) inhibits insulin though what receptor activation?

A

A-receptor

62
Q

B2 receptor activation (inc./dec.) insulin secretion

A

increases

63
Q

glucagon released in response to low BG stimulates glucose release from which organ?

A

liver

64
Q

High BG causes insulin to make which cells take up glucose?

A

fat cells

65
Q

glucose is brought into the b-cell by which GLUT?

A

GLUT1

66
Q

what is the rate limiting step of gluocose metabolism in b-cells/

A

glucose phosphorylation by glucokinase (hexokinase IV)

67
Q

formation of G6P leads to the elevation of the ATP/ADP ratio and the production of…..

A

NADPH

68
Q

Elevated ATP inhibits the (blank) channel leading to cell membrane depol. after the formation of G6P

A

ATP sensitive K channel (Katp Kir6.2)

69
Q

Depolarization of the b-cell membrane after K channel inhiibition leads to increased (blank) influx along with mobilization of (blank) from intracellular stores

A

Ca

70
Q

Increased intracelular Ca in the b-cells leads to fusion of (blank) with the plasma membrane

A

exocytosis of insulin and C peptide via granule fusion with the PM

71
Q

Which neurotransmitter stimulates the release of insulin?

A

ACh

72
Q

which two strange hormones stimulate the release of insulin?

A

glucagon like peptide 1

incretins

73
Q

(blank) synergizes with glucagon like peptide 1 and incretins and enhances insulin secretion

A

glucose

74
Q

what drug stimulates the Kir6.2 ATP sensitive K channel?

A

Diazoxide

75
Q

What two drugs inhibit the Kir6.2 ATP sensitive K channel?

A

sulfonylurea/meglitinide

76
Q

t/f: the majority of circulating insulin is protein bound

A

false; unbound!!

77
Q

the volume of distribution of insulin approximates the volume of…

A

Extracellular volume

78
Q

what is the half life of basal circulating insulin?

A

9 minutes or less

79
Q

t/f: the half life of circulating insulin is reduced in diabetics

A

false; same for diabetics and normal people

80
Q

Which organ is responsible for greater than 50% of insulin clearance and metabolism?

A

liver

81
Q

what organ handles the remainder of insulin degradation?

A

kidney

82
Q

At the cellular level, what is the first step in insulin degradation?

A

binding of insulin to its receptor to from a complex

83
Q

Insulin-receptor complex internalization results in proteolytic degradation of insulin by (blank) mediated hydrolysis

A

thiol metalloproteinase; breaks the disulfide link between A and B chains

84
Q

After insulin has been degraded, what is the fate of the insulin receptor?

A

returns to cells surface

85
Q

t/f: insulin is filtered by the glomerulus

A

true

86
Q

What cells in the nephron absorb insulin?

A

tubular epithelial cells; also degrade insulin

87
Q

what is insulin’s affect on liver glucose production?

A

dec. gluconeogenesis

dec. glycogenolysis

88
Q

what is insulin’s affect on liver glucose uptake and glycolysis?

A

increased

89
Q

what is insulin’s affect on liver on TG synth?

A

increased

90
Q

what is insulin’s affect on liver protein synth?

A

increased

91
Q

insulin decreases muscle glucose production by decreasing transfer of what three gluconoegenic precursors to the liver/

A

alanine
lactate
pyruvate

92
Q

What is the affect of insulin on glucose uptake and glycolysis on liver, muscle, and fat?

A

increased

93
Q

How does insulin affect muscle glycogen synthesis?

A

increased

94
Q

How does insulin affect muscle protein synthesis/

A

increased

95
Q

insulin decreases fatglucose production by decreasing transfer of what two gluconoegenic precursors to the liver/

A

glycerol and energy for liver gluconeogenesis

96
Q

In order to uptake glucose, GLUT transporters are translocated to the….

A

PM

97
Q

what three enzyme activities are altered in response to insulin?

A
  1. increased glucokinase (bring glucose into the cell)
  2. increased glycogen synthase (store the glucose)
  3. dec. glycogen phosphorylase (prevent glycogen breakdown)
98
Q

t/f: insulin alters gene transcription

A

true

99
Q

insulin promotes the uptake of what ion into the cell?

A

K

100
Q

which GLUT is translocated to the cell surface upon insulin binding?

A

GLUT4

101
Q

activation of Shc and Gab1 lead to the activation of the MAP kinase pathway which has what affect on the cell?

A

cell growth, differentiation, and surivival

102
Q

IRS proteins activate the PI3-kinase pathway which stimulates the synthesis of..

A

protein and glycogen

103
Q

What pathway leads to the translocation of GLUT4 to the cell surface?

A

IRS and Cbl

104
Q

insulin acts with the receptor via which chain?

A

B chain

105
Q

Type I DM is insulin dependent or resistant?

A

dependent; due to lack of functional B cells

106
Q

in Type Ia DM that is autoimmune, Abs form against what two things?

A

b-cells and glutamic acid decarboxylase

107
Q

90% of US cases of diabetes are…

A

type II

108
Q

in what type of diabetes is ketoacidosis common?

A

type I

109
Q

What is the twin concordance in type I DM?

A

30-70%

110
Q

what is the twin concordance in type II DM?

A

50-90%

111
Q

which type of DM is linked ot MHC class II HLA genes?

A

type I

112
Q

type I DM destruction of b-cells is T cell meidated via what cytokines?

A

TNF
IL1
NO

113
Q

describe the histological changes in type 1 DM

A

atrophy and fibrosis

114
Q

describe the histological changes in type 2DM

A

focal atrophy and amyloid deposition

115
Q

what effect does EtOH have on blood sugar?

A

inhibits gluconeogenesis

116
Q

b-agonists cause hyperglycemia by what two methods?

A
  1. stimulate insulin release

2. inc. liver glycogenolysis

117
Q

in diabetics, (blanks) have the risk of hypoglycemai due to inhibition of catecholamine induced gluconeogenesis and glyocogenolysis

A

b-blockers

118
Q

B-blockers may mask what symptoms of hypoglycemia?

A

tremor, palpitations, perspriation

119
Q

How do salicylates cause hypoglycemia?

A
  1. enhancing pancreatic b-cell sensitivity to glucose
120
Q

what are the complications of diabetes?

A 
Retinopathy
Feet ulceration
Nephropathy
Cardiomyopathy
Neuropathy
Loss of sensibility in inferior extremities (legs)
121
Q

What are the lifestyle changes for diabetes?

A
  1. inc. physical activity (walk 30mins)

2. lots of veggies/fruits, low in fat and carbs

122
Q

What is the target HbA1C in T2DM?

A

less than 7

123
Q

what is the target preprandial glucose in T2DM?

A

70-130

124
Q

what is the target postprandial glucose in T2DM?

A

less than 180

125
Q

what is the target blood pressure in T2DM?

A

less than 130/80

126
Q

What should the lipid panel look like in T2DM?

A 
LDL:   < 100 mg/dL 
           < 70 mg/dL  if CVD
HDL:   > 40 mg/dL 
            > 50 mg/dL if CVD
TG:      < 150 mg/dL
127
Q

Describe the individualization of HbA1c:

A

tighter targets: 6-6.5 if young and healthy

Looser targets: 7.5-8+ if older with comorbidities

Block 10 Week 2 (6 decks)

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