Duan > Insulin & Oral hypoglycemics (RED TEXT ONLY) Flashcards
(127 cards)
1
Q
what does the maintenance of glucose homeostasis involve?
A
integration of several major organs via multilayered inter-organ communication
2
Q
where does insulin come from?
A
pancreatic beta cells
3
Q
what is central to the glucose homeostasis process?
A
adjustment of the amt of insulin that comes from beta cells
4
Q
where does glucagon come from?
A
alpha cells
5
Q
where does insulin come from?
A
beta cells
6
Q
how are basal levels of circulating insulin maintained (post-absorptive)?
A
constant beta cell secretion
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
8
Q
when is glucagon released?
A
when blood sugar is low
9
Q
what does glucagon do?
A
releases glucose from tissues back into blood
10
Q
where is insulin synthesized?
A
beta cells
as PROINSULIN
11
Q
HOW is insulin formed?
A
proinsulin > proteolysis > insulin + C-peptide + 4 AAs
12
Q
what is the structure of insulin?
A
A chain + B chain
joined by 2 interchain disulfide bonds
13
Q
which chain of insulin has an interchain bond?
A
A chain
14
Q
what are the 3 possible forms of insulin?
A
monomer
dimer
hexamer coordinated by 2 Zn atoms
15
Q
what is the biologically active form of insulin?
A
monomer
16
Q
what is the standard insulin preparation?
A
human insulin prep (Humulin) made as the recombinant protein
17
Q
which has a greater capacity to stimulate insulin secretion: oral glucose or IV glucose?
A
ORAL!
18
Q
what 3 components of food stimulate insulin secretion?
A
glucose
amino acids (arg, lys)
FAs & ketones
19
Q
what regulates insulin release (think autonomic mechanisms)
A
Hypothalamus
Ventrolateral (vagus)
Ventromedial (sympathetic)
20
Q
how does vagal/parasympathetic stimulation impact insulin release?
A
activates M receptors > INC insulin release
para is rest & digest
21
Q
how does sympathetic stimulation impact insulin release?
A
activates alpha-receptors > DEC insulin release
however
beta 2 activation INC insulin release
22
Q
how do insulin and glucagon interact?
A
Glucagon stimulates insulin secretion
Insulin inhibits glucagon secretion
23
Q
how is glucose transferred into beta cells in humans?
A
GLUT1
24
Q
what is the RLS in glucose metabolism in the beta cell?
A
glucose phosphorylation by glucokinase
25
what process leads to insulin release from beta cells (kinda long sorry)
INC ATP > inhibit ATP-sensitive K channel > depol > Ca influx > storage granule fusion > exocytosis of insulin + C-peptide
26
what 2 other factors (plus a mediator) can stimulate insulin release (besides food)
NTs (ACh)
Hormones (glucagon-like peptide 1 & incretins)
Glucose ENHANCES these
27
what is the fate of insulin?
insulin-receptor complex internalization > proteolysis by thiol metalloproteinase hydrolysis of the di-S linkage btwn A & B chains > receptor returns to cell surface
28
which cells degrade insulin?
tubular epithelial cells (kidney)
29
what are the principle targeting tissues for insulin regulation of glucose?
liver
muscle
fat
30
what does insulin STIMULATE (which processes)?
utilization & storage of glucose, AAs, & FAs
31
what does insulin INHIBIT (which processes)?
breakdown of glycogen, protein, & fat
32
what controls glucose metabolism?
increasing glucokinase activity, stimulating glycogen synthase, & inhibiting glycogen phosphorylase
33
generally, what is DM1?
lack of fxnal beta cells
| either autoimmune or not
34
generally, what is DM2?
inadequate insulin response (normal insulin levels but ineffective > insulin resistance)
35
go thru Dr. Usera's flash cards for the pancreas to learn about DM1 & DM2 & their sx & presentations
okie dokie
36
what meds pose a risk of hypoglycemia in diabetic pts & can cause secondary DM?
beta blockers
COLT DO NOT GET DIABETES
37
what are the 3 lifestyle changes you can implement to treat DM?
inc physical activity
appropriate diet
body weigh optimization
38
what 2 general classes of meds can you give for DM?
1. insulin
| 2. hypoglycemics (oral or non-insulin injectables)
39
what are incretins?
hormones that the gut releases thruout the day; increase when you eat
40
what are the 2 major incretins?
GIP > glucose-dependent insulinotropic peptide
| GLP-1 > glucagon-like peptide 1
41
what do incretins do?
facilitate the response of the pancreas & liver to glucose fluctuations via acting on pancreatic alpha & beta cells
42
what happens to incretins in DM2?
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)
43
TO THE DRUG TABLES
LET'S GO
44
what is normal fasting blood glucose?
70-99
45
what is normal blood glucose two hours after a meal?
<140
46
t/f: insulin is stored in beta cells
true
47
constant b-cell secretion maintains low basal levels of circulating insulin during what period of time?
post-absorptive, aka between meals
48
basal insulin secretion suppresses what three processess?
lipolysis
proteolysis
glycogenolysis
49
Insulin is released in a bolus after ingestion of glucose or....
amino acids
50
Proteolysis of insulin results in three components?
insulin, C peptide, and four basic amino acids
51
What atom links the polymers of insulin?
Zn
52
t/f: orally ingested glucose results in greater insulin stimulation than intravenous stimulation
true
53
Gastrin, CCK, and GIP augment (blank) secretion
insulin
54
What axis is responsible for digestion, absorption and regulation of utilization of foods?
enteropancreatic
55
Which two particular amino acids stimulate insulin secretion?
Arginine and lysine
56
What are the four molecules that can stimulate insulin secretion?
1. glucose
2. AA's (Arg, Lys)
3. FA
4. ketone bodies
57
Which vagal system regulates autonomic release of insulin?
ventrolateral system
58
Which two sympathetic systems regulate autonomic release of insulin?
ventromedial and hypothalamic
59
Vagal (aka parsymp) stimulation or cholinomimetic drugs increase insulin release through what receptor?
M receptor
60
Exercise, hypoxia, hypothermia, trauma, or burns does what to insulin secretion?
inhibits it
61
sympathetic stim (Exercise, hypoxia, hypothermia, trauma, or burns) inhibits insulin though what receptor activation?
A-receptor
62
B2 receptor activation (inc./dec.) insulin secretion
increases
63
glucagon released in response to low BG stimulates glucose release from which organ?
liver
64
High BG causes insulin to make which cells take up glucose?
fat cells
65
glucose is brought into the b-cell by which GLUT?
GLUT1
66
what is the rate limiting step of gluocose metabolism in b-cells/
glucose phosphorylation by glucokinase (hexokinase IV)
67
formation of G6P leads to the elevation of the ATP/ADP ratio and the production of.....
NADPH
68
Elevated ATP inhibits the (blank) channel leading to cell membrane depol. after the formation of G6P
ATP sensitive K channel (Katp Kir6.2)
69
Depolarization of the b-cell membrane after K channel inhiibition leads to increased (blank) influx along with mobilization of (blank) from intracellular stores
Ca
70
Increased intracelular Ca in the b-cells leads to fusion of (blank) with the plasma membrane
exocytosis of insulin and C peptide via granule fusion with the PM
71
Which neurotransmitter stimulates the release of insulin?
ACh
72
which two strange hormones stimulate the release of insulin?
glucagon like peptide 1
| incretins
73
(blank) synergizes with glucagon like peptide 1 and incretins and enhances insulin secretion
glucose
74
what drug stimulates the Kir6.2 ATP sensitive K channel?
Diazoxide
75
What two drugs inhibit the Kir6.2 ATP sensitive K channel?
sulfonylurea/meglitinide
76
t/f: the majority of circulating insulin is protein bound
false; unbound!!
77
the volume of distribution of insulin approximates the volume of...
Extracellular volume
78
what is the half life of basal circulating insulin?
9 minutes or less
79
t/f: the half life of circulating insulin is reduced in diabetics
false; same for diabetics and normal people
80
Which organ is responsible for greater than 50% of insulin clearance and metabolism?
liver
81
what organ handles the remainder of insulin degradation?
kidney
82
At the cellular level, what is the first step in insulin degradation?
binding of insulin to its receptor to from a complex
83
Insulin-receptor complex internalization results in proteolytic degradation of insulin by (blank) mediated hydrolysis
thiol metalloproteinase; breaks the disulfide link between A and B chains
84
After insulin has been degraded, what is the fate of the insulin receptor?
returns to cells surface
85
t/f: insulin is filtered by the glomerulus
true
86
What cells in the nephron absorb insulin?
tubular epithelial cells; also degrade insulin
87
what is insulin's affect on liver glucose production?
dec. gluconeogenesis
| dec. glycogenolysis
88
what is insulin's affect on liver glucose uptake and glycolysis?
increased
89
what is insulin's affect on liver on TG synth?
increased
90
what is insulin's affect on liver protein synth?
increased
91
insulin decreases muscle glucose production by decreasing transfer of what three gluconoegenic precursors to the liver/
alanine
lactate
pyruvate
92
What is the affect of insulin on glucose uptake and glycolysis on liver, muscle, and fat?
increased
93
How does insulin affect muscle glycogen synthesis?
increased
94
How does insulin affect muscle protein synthesis/
increased
95
insulin decreases fatglucose production by decreasing transfer of what two gluconoegenic precursors to the liver/
glycerol and energy for liver gluconeogenesis
96
In order to uptake glucose, GLUT transporters are translocated to the....
PM
97
what three enzyme activities are altered in response to insulin?
1. increased glucokinase (bring glucose into the cell)
2. increased glycogen synthase (store the glucose)
3. dec. glycogen phosphorylase (prevent glycogen breakdown)
98
t/f: insulin alters gene transcription
true
99
insulin promotes the uptake of what ion into the cell?
K
100
which GLUT is translocated to the cell surface upon insulin binding?
GLUT4
101
activation of Shc and Gab1 lead to the activation of the MAP kinase pathway which has what affect on the cell?
cell growth, differentiation, and surivival
102
IRS proteins activate the PI3-kinase pathway which stimulates the synthesis of..
protein and glycogen
103
What pathway leads to the translocation of GLUT4 to the cell surface?
IRS and Cbl
104
insulin acts with the receptor via which chain?
B chain
105
Type I DM is insulin dependent or resistant?
dependent; due to lack of functional B cells
106
in Type Ia DM that is autoimmune, Abs form against what two things?
b-cells and glutamic acid decarboxylase
107
90% of US cases of diabetes are...
type II
108
in what type of diabetes is ketoacidosis common?
type I
109
What is the twin concordance in type I DM?
30-70%
110
what is the twin concordance in type II DM?
50-90%
111
which type of DM is linked ot MHC class II HLA genes?
type I
112
type I DM destruction of b-cells is T cell meidated via what cytokines?
TNF
IL1
NO
113
describe the histological changes in type 1 DM
atrophy and fibrosis
114
describe the histological changes in type 2DM
focal atrophy and amyloid deposition
115
what effect does EtOH have on blood sugar?
inhibits gluconeogenesis
116
b-agonists cause hyperglycemia by what two methods?
1. stimulate insulin release
| 2. inc. liver glycogenolysis
117
in diabetics, (blanks) have the risk of hypoglycemai due to inhibition of catecholamine induced gluconeogenesis and glyocogenolysis
b-blockers
118
B-blockers may mask what symptoms of hypoglycemia?
tremor, palpitations, perspriation
119
How do salicylates cause hypoglycemia?
1. enhancing pancreatic b-cell sensitivity to glucose
120
what are the complications of diabetes?
```
Retinopathy
Feet ulceration
Nephropathy
Cardiomyopathy
Neuropathy
Loss of sensibility in inferior extremities (legs)
```
121
What are the lifestyle changes for diabetes?
1. inc. physical activity (walk 30mins)
| 2. lots of veggies/fruits, low in fat and carbs
122
What is the target HbA1C in T2DM?
less than 7
123
what is the target preprandial glucose in T2DM?
70-130
124
what is the target postprandial glucose in T2DM?
less than 180
125
what is the target blood pressure in T2DM?
less than 130/80
126
What should the lipid panel look like in T2DM?
```
LDL: < 100 mg/dL
< 70 mg/dL if CVD
HDL: > 40 mg/dL
> 50 mg/dL if CVD
TG: < 150 mg/dL
```
127
Describe the individualization of HbA1c:
tighter targets: 6-6.5 if young and healthy
| Looser targets: 7.5-8+ if older with comorbidities
