Mastick BCH Insulin and Glucagon Flashcards
1
Q
What is this:
autoimmune destruction of beta cells
A
Type 1 diabetes
2
Q
What is this:
B cell exhaustion; compensation for insulin resistance
A
Type II diabetes
3
Q
What is the primary defect of type 1 diabetes and how do fix this?
A
No insulin
insulin injections required or islet transplant
4
Q
What is the secondary defect of type 2 diabetes?
How do you fix this?
A
not enough insulin oral hypoglycemics (work to lower your blood sugar)
5
Q
Where in the US is diabetes the worst?
A
the south
6
Q
The diabetes epidemic has turned into the diabetes tsunami because a ….
A
higher percentage of pop are becoming diabetic
7
Q
(blank) % of the population have diabetes
A
8.3%
8
Q
What are complication associated with diabetes?
A
heart disease and stroke high blood pressure blindness kidney disease nervous system disease (neuropathy) amputation
9
Q
What endocrine hormones does the pancreas secrete?
A
insulin, glucagon, somatostatin
10
Q
(blank) is richly vascularized and innervated by sympathetic and parasympathetic fibers.
A
pancreas
11
Q
What are the 2 components of the pancreas?
A
acini and islets of langerhans
12
Q
What secrete digestive juices into duodenum?
A
acini
13
Q
What secrete insulin and glucagon into blood (separated from the acini by CT capsule)?
A
Islet of Langerhans
14
Q
What are the three types of cells that the islets of langerhan contain?
What is the most abundant?
A
Alpha cells
beta cells
delta cells
Beta cells are the most abundant
15
Q
TO maintain glucose homeostasis, blood glucose levels should be at around (blank)
A
5.5
16
Q
(blank) is an anti-hyperglycemic
A
insulin
17
Q
(blank) is an anti-hypoglycemic
A
glucago
18
Q
(blank) is a tonic modulator
A
somatostatin
19
Q
What keeps levels of the secretion of insulin and and glucagon constant?
A
somatostatin
20
Q
Explain what happens to proglucagon
A
Proglucagon can either leave the ER and go into vesicles to become glucagon in pancreatic islet alpha cells or can go into intestinal L cells and STN neurons to become oxyntomodulin
21
Q
Explain what happens to preproinsulin?
A
Pre form allows (preproinsulin) of insulin allows the pro form to be folded properly, it is cleaved and becomes insulin and a C peptide
22
Q
(blank) has a short half life.
A
Insulin
23
Q
(blank) levels are measured to see insulin levels due to the fact that they are in the same secretory granules and are in a one to one ratio with insulin.
A
C peptide
24
Q
What three cell types are intercalated and communicate with each other?
A
insulin, glucagon, somatostatin
25
What are the four phases of glucose homeostasis during fasting?
well fed
post absorptive
gluconeogenic (early)
prolonged
26
When you have prolonged fasting up to 42 days what happens to your glucose levels?
they remain relatively stable and steady
27
When you eat what happens to your glycogen levels? WHen you start to use up your glycogen what happens?
They increase
| you start to increase gluconeogenesis
28
```
During phase 1:
What is the nutritional status?
What is the origin of the blood glucose?
What tissues are using glucose?
What is the major fuel of the brain?
```
well fed
exogenous
all
glucose
29
```
During phase 2:
What is the nutritional status?
What is the origin of the blood glucose?
What tissues are using glucose?
What is the major fuel of the brain?
```
- post-absorptive
- hepatic glycogen, gluconeogenesis
- all except liver. Muscle and adipose at diminished rates
- glucose
30
```
During phase 3:
What is the nutritional status?
What is the origin of the blood glucose?
What tissues are using glucose?
What is the major fuel of the brain?
```
gluconeogenic (early)
hepatic and renal gluconeogenesis
Brainand RBCs; small amount by muscle
glucose, ketone bodies
31
```
During phase 4:
What is the nutritional status?
What is the origin of the blood glucose?
What tissues are using glucose?
What is the major fuel of the brain?
```
Prolonged
renal and hepatic gluconeogenesis
RBCs, Brain at dimished rate
ketone bodies, glucose
32
What happens if glucohomeostasis fails?
death
33
If your blood glucose level is above 8 whats up?
hyperglycemia !!!
34
If your blood glucose levels are slightly higher than 5.5 whats up?
normoglycemia fed state; insulin secretion increase which inhibits glucagon secretion
35
If your blood glucose levels are at 5.5 whats up?
normoglycemia fasting
36
If your blood glucose levels are at 4.6 whats up?
normoglycemia under a load (heavy physical exercise) insulin secretion decreases, which causes glucagon secretion to increase
37
If you are at 3.8 glucose whats up?
hypoglycemia, increase secretion of adrenaline and growth hormone
38
What are these:
3. 2 Cortisol secretion.
2. 8 Confusion.
1. 7 Weak, sweat, nauseous.
1. 1 Muscle cramps.
0. 6 Brain damage, death.
problems arising from decreased blood glucose
39
What does a glucose tolerance test do and how does it work?
adults are given 75g of glucose and some water.
Watch reaction
Normal: glucose levels remain below 200
Diabetes: glucose levels are higher than 200
40
What is this:
| Exceeds renal threshold for uptake of glucose from pre-urine, diuresis (loss of glucose, water, Na+and K+ in urine).
hyperglycemia
41
Is acute hyperglycemia life threatening?
no the problem arises to chronic exposure to glucose
42
(blank) is reactive and inactives proteins and such so it can cause a lot of complications.
glucose
43
Does a meal always decrease glucagon secretion?
no
44
When a meal decreases glucagon secretion, is the effect big or small?
small!
45
Under normal circumstances, when you have a meal your (blank) levels will change a lot and your (Blank) levels will only change slightly
insulin
| glucagon
46
A high (blank) meal increases the secretion of both glucagon and insulin
protein (or arginine)
47
(blank) percent of glucose goes to brain
60%
48
Alpha cells make (blank) and beta cells make (blank)
glucagon
| insulin
49
During an overnight fast, the insulin/glucagon ratio favors (blank)
glucose secretion (glycogenolysis, gluconeogenesis)
50
During an overnight fast, glucose storage is (blank) in the liver
inhibited
51
During an overnight fast, lipolysis is (blank) and lipogenesis is (blank)
stimulated
| inhibited
52
Is there an effect on glucagon on peripheral tissues?
NOOOO only liver
53
During an overnight fast, low (blank) favors breakdown of glucose stores(glycogenolysis) and inhibits formation of glucose stores in (Blank). This reduces the amount of glucose required from the blood.
insulin
54
Resting glucose transport is decreased 3-4 fold relative to the fed (high insulin) state, but can be fully stimulated by (blank)
exercise or other stimuli AMPK
55
If muscles are being pushed (higher energy states) then high (blank) will stimulate glucose transport from blood
AMPK
56
Glucose incorporation into triglyceride (lipogenesis) is (blank) by glucose transport in adips. No hormones are required to maintain low basal rate.
(adipocytes are full of energy, dont really care about getting glucose)
rate limited
57
(blank) is the major site of glucose disposal after a meal
muscle
58
During fed metabolic state (prandial/during meals), insulin/glucagon ratio inhibits (blank) secretion and stimulates (blank) in the liver.
glucose
| glucose storage
59
During the fed state (blank) is inhibited.
lipolysis
60
(blank) increases glucose transport 4-fold in muscle. This is rate limiting, and stimulation of this step is essential for efficient glucose clearance from the blood.
high insulin
61
Glucose transport to the muscles can be fully stimulated by (blank) even in insulin resistant states
exercise
62
High insulin stimulates (blank) and inhibits (blank) in the muscle.
```
glucose storage (glycogen synthesis)
glycogen breakdown (glyogenolysis)
```
63
(blank) increases glucose transport 20-50-fold in adipocytes!
High insulin
64
```
Very low (basal fasting) levels of insulin are sufficient to (blank) breakdown of fat (lipolysis) in adipose tissue.
Therefore what is needed to stimulate lipolysis in fat?
```
inhibit
| other hormones
65
extreme exercise can cause (blank)
hypoglycemia
66
PP1 does what?
Turns glucose into glycogen or fat
67
What does PKA do?
Turns glycogen into glucose
68
GLucose enters cells through (blank)
facilitative GLUTs
69
TO keep glucose inside of cell once it is transported, there are enzymes inside the cell that (blank) the glucose (hexokinase or glucokinase) which will make it so that glucose is stuck inside cell. So you have very low levels of free glucose in cell because it is phosphorylated so quickly. Is this reversible?
phosphorylate
| ONLY in liver!!! No where else
70
What transporter has highest affinity?
glut 3 for the brain
71
What transporter has low affinity?
| Do they work at max efficiency?
```
Glut 2 (liver, pancreatic b cells, intestine)
NO
```
72
What receptors do you find on skeletal and fat?
high affinty GLUT 4
73
Where do you find glut 1 and is it high or low affinity
high
| pancreatic alpha cells and most other tissues
74
(blank) secretion is low at basal glucose concentrations, high at fed glucose levels
Insulin
75
(blank) secretion is low at basal glucose concentrations, because ATP/ADP ratio is low.
insulin
76
At low glucose, there is a low (blank) ratio
ATP/ADP
77
What happens when you have low glucose?
Low glucose->Low ATP-> K channel active-> Ca channel inhibited-> insulin secretion is inhibited
78
What happens when you have high amounts of glucose?
High ATP-> inhibition of K channel-> activation of Ca channel-> increase in insulin secretion
79
(blank) secretion increases as the [glucose] increases and the ATP/ADP ratio increases
Insulin
80
What is this:
small changes in [glucose] are amplified due to the low affinity of the glucose transporter and glucose-kinase isoforms expressed in β cells
glucose sensing
81
(blank) is a Low affinity (Km = 15 mM), high capacity glucose transporter
GLUT 2
82
(blank) is a low affinity (Km = 10 mM), high capacity kinase
Glucokinase
83
(blank) is also dependent on the ATP/ADP ratio in α cells, but this does not change
much at physiological glucose concentrations!
glucose sensing
84
(blank) is a High affinity (Km = 1 mM), low capacity glucose transporter
Glucokinase- low affinity (Km = 10 mM), high capacity kinase
GLUT1
85
Glucose sensing: the effect of changes in [glucose] on ATP/ADP are muted due to the
high affinity of the glucose transporter isoform expressed in (blank)
α cells
86
There are (blank) mechanisms of control of glucagon secretion
multiple alternative mechanisms
87
In peripheral tissues, glucose transport is rate limited by the total number of (blank)
inserted into the plasma membrane (each is working at maximum capacity)
transporters
88
(blank) - High affinity (Km = 1 mM), low capacity glucose transporter
(blank) - High affinity (Km = 10 μM), low capacity kinase
GLUT4
| Hexokinase
89
Insulin stimulates glucose transport in (blank) 20-50 fold, but only 3-4 fold in
(blank).
fat
| muscle
90
The (blank) are nearly saturated at 4 mM glucose, therefore, there is no change in glucose uptake in cells expressing these transporters under normal physiological blood glucose levels UNLESS the total number of glucose transport proteins at the cell surface changes (GLUT4, the insulin-responsive transporter).
The high affinity glucose transporters (GLUTs 1,3,4
91
The (blank) is not saturated at physiological blood glucose concentrations, therefore, glucose uptake changes over all ranges of physiological glucose in cells expressing these transporters (beta cells and liver).
the low affinity glucose transporter GLUT 2
92
Why do you need a tonic regulator if it is the insulin/glucagon ratio that determines
the flux of glucose into and out of the blood?
YOu would get out of control high levels of these hormones without a tonic regulator
93
(blank)
| Acts as tonic inhibitor- limits how much of both are released, but does not affect when
somatostatin
94
(blank) Work directly on the ATP sensitive potassium channel. They inhibit this channel which allows calcium to flow in which allows direct stimulation of insulin secretion into the blood from pancreatic beta cells
sulfonylureas
95
(blank) work at level o beta cell-> bind to specific receptor on beta cells and make the cell more susceptible to stimulation to secrete insulin
incretins
96
What do these do:
Sulfonylureas (Diabeta, Glucotrol, Amaryl)- KATP channel modulators β- CELLS
Other Secretagogues (Starlix, Prandin)- KATP channel modulators β- CELLS
Incretin analogues (Exendin-4, Exenatide)- GLP-1 receptor agonists β- CELLS
DPP-4 Inhibitors (Januvia, Onglyza)- slows incretin turnover β- CELLS
increased insulin secretion
97
What do these do:
Biguanides (Metformin)- activates AMPK (indirect), insulin sensitizer MUSCLE
Thiazolidinediones (Avandia, Actos)- PPAR-γ activator, insulin sensitizer ADIPOSE
increased insulin sensitivity
98
What do these do:
| α-Glucosidase inhibitors (Acarbos)- inhibits intestinal uptake of starch INTESTINE
decreased glucose absortion
99
What does metformin do?
mimics exercise
100
Cant you treat T1D with oral hypoglycemics?
no you need insulin injections or islet transplant
101
Cant you treat T2D with oral hypoglycemics?
yes and insulin injections
102
In the "basal" state, there is enough insulin to (blank) lipolysis, but it is a very low level. If there is another hormone around like epinephrine or cortisol, they win, and you have lipolysis.
After a meal, insulin increases to high levels. Under these conditions insulin wins and (blank) lipolysis, even if other hormones are present.
inhibit
| turns off
103
What does AMPK do in muscle?
stimulation of muscle glucose uptake and sitmulates insulin secretion
104
What does G6Pase do?
it is the last step before getting glucose (i.e of gluconeogenesis or glycogenolysis) and it cleaves the phosphate off of G6P to make Glucose and it is THE ONLY way you can get glucose out of the liver
105
If you have an issue with G6dehydrogenase what can results?
Hemolytic anemia
