Module 5 Flashcards
Incretin Secretion is stimulated by:
a) Spike in insulin levels
b) TAG breakdown
c) Reabsorption
d) Food intake
e) none of the above
d) Food intake;
Regulation of incretin secretion (topic)
Q: Polarized cells that sense the contents of the intestinal lumen called?
a) K cells
b) L cells
c) GIP
d) Enteroendocrine cells
e) Epithelial cells
f) Enterocytes
d) enteroendocrine cells
____ is released from K cells and ____ is released from L cells in response to nutrients in the intestinal lumen
GIP
GLP-1
True or False:
Pro-GIP is processed using PC1 to make its active form which is stored in vesicles
FALSE: it is processed by PC2
True or False:
Pro-GLP-1 is processed using PC1 to make its active form, which is stored in vesicles
TRUE
Which has a higher peak (and generally higher basal) in blood levels? and what are the values as a bonus
a) GLP-1
b) GIP
c) depends
d) both are equal
b) GIP
Basal= 10 pmol/L
Peak = 150-300 pmol/L
How were incretins discovered? What was observed in this study?
- intestinal extracts from a pig were administered to patients 3x a day
- improvements in glucose homeostasis
What is an incretin?
peptide hormones secreted from the gut
True or False:
The incretin effect says that an oral glucose load produces a REDUCED response compared to an isoglycemic IV glucose infusion.
FALSE- it produces an INCREASED response
- If someone had an impaired insulin response and needed considerable improvement, what would you do?
a) administer glucose via oral intake
b) administer via an isoglycemic IV glucose infusion - What if it was imperative (life or death) that they were able to clear the glucose from their blood after ~ 1 hour?
a) administer glucose via oral intake
b) administer via an isoglycemic IV glucose infusion
THE INCRETIN EFFECT:
1. a) oral glucose
2. still oral, IV takes a while to clear from the blood
Explain the study on the Incretin effect in mice that was completed and what it showed.
- oral glucose = **insulin spike; helps reduce bl glucose levels more effectively
- compared mice fed a normal diet vs mice fed a high-fat diet, measured both of their blood glucose and insulin levels
** no spike in insulin levels
** GLUCOSE: - 1 hour- oral vs IV were same levels ish
- CHANGE occurred in 2nd hour when they saw bl glucose from IV was higher
** this showed that IV administered glucose is not cleared as effectively from the blood.
Carbs (glucose) are potent stimulators of incretins through 2 mechanisms:
- SGLT-1; acts on transporter substrates
- Sweet taste receptors (Tas1R2, Tas1R3); act on Gs-coupled receptors
both of these mechanisms;
- lead to cell depolarization
- inc Ca2+ levels
- cause incretin-containing vesicles to release contents into circulation
True or False: SGLT-1 is necessary for lipid-dependent incretin secretion
FALSE: it is necessary for GLUCOSE dependent.
Following meal consumption, incretin response is rapid and persists for several _____; incretins are activated by ____
a) mins, DPP-4
b) secs, DPP-2
c) hours, DPP-4
d) days, DPP-2
c) hours, DPP-4
Is the half-life of GLP-1 or GIP longer?
GIP; it is 7 mins
True or False:
water intake increases active levels of GLP-1
False; water intake has no effect on incretin secretion
Obesity has _____ on GIP secretion and _____ on GLP-1 secretion
a) no effect on both
b) positive effect; negative effect
c) negative effect; no effect
d) no effect; negative effect
e) no effect; positive effect
f) positive effect; no effect
g) negative effect; positive effect
d) no effect; neg effect
In general, what effect does obesity have on active incretin levels in circulation?
a) no effect
b) negative effect
c) positive effect
b) negative effect, causes a general reduction
T/F; consumption of different macronutrients increases total and active levels of both GIP and GLP-1 in the blood.
TRUE
In the pancreas, incretins combine with ____ to _____ insulin release into the blood
glucose; increase
Correct sequence of the role of incretins in the pancreas:
a) binds to specific receptors→ formation of cAMP → decreases Ca2+ intracellular levels (hyperpol) → exocytosis of insulin granules → insulin release into blood
b) binds to specific receptors→ formation of cAMP → increases Ca2+ intracellular levels (depol) → exocytosis of insulin granules → insulin release into blood
c)binds to specific receptors→ formation of cAMP → increases Ca2+ intracellular levels (depol) → endocytosis of insulin granules → insulin release into blood
d) binds to specific receptors → increases Ca2+ intracellular levels (depol) → exocytosis of insulin granules → insulin release into blood
e) binds to specific receptors→ formation of cAMP → exocytosis of insulin granules → inc Ca2+ intracellular levels (depol) → insulin release into blood
e) binds to specific receptors→ formation of cAMP → exocytosis of insulin granules → inc Ca2+ intracellular levels (depol) → insulin release into blood
Incretins decrease:
a) appetite
b) insulin secretion
c) insulin sensitivity
d) cardiac output
e) gastric emptying
f) glucose production
SELECT ALL THAT APPLY
aef
- appetite, gastric emptying, glucose production
Incretins Increase:
a) b cell apoptosis
b) glucagon secretion
c) insulin biosynthesis
d) insulin sensitivity
e) cardiac output
f) glucose production
ALL THAT APPLY
c,d,e
- insulin biosynthesis, insulin sensitivity, cardiac output
Obesity & T2D cause _____ in incretin response
a) increase
b) decrease
c) no effect
b) decrease
Incretin Mimetics:
a) create incretin with a longer half life
b) block DPP4 enzyme directly
c) are modified to resist DPP4 inactivation
d) cause incretin levels to be preserved longer
e) have a similar structure to incretin
f) a, b, e
g) a, c, e
h) b, d, e
i) b,c,d
g) ace
- similar structure to incretin but modified to resist DPP4 inactivation→ Incretin with a longer half-life created
Incretin Enhancers:
a) create incretin with a longer half life
b) block DPP4 enzyme directly
c) are modified to resist DPP4 inactivation
d) cause incretin levels to be preserved longer
e) have a similar structure to incretin
f) a, b
g) a, c
h) b, d
i) b,c
h) b, d
- block DPP4 enzyme directly, natural incretin levels are preserved for longer
Example of incretin mimetic
Exanatide
Study using an incretin mimetic:
what happened when patients with T2D were treated with an inc mimetic for 3 years: ALL THAT APPLY
a) dec body weight
b) inc body weight
c) dec ALT (healthier liver)
d) inc ALT (healthier liver)
e) Dec HbA1c
f) inc HbA1c
g) dec blood triglycerides/cholesterol/ LDL cholesterol/ BP
h) inc blood triglycerides/cholesterol/ LDL cholesterol/ BP
i) dec HDL-cholesterol
j) inc HDL-cholesterol
a) dec body weight
c) dec ALT–> healthier liver
e) dec HbA1c
g) dec TGs, cholest, LDL cholest, BP
j) inc HDL cholest
what does a DPP-4 inhibitor do?
a) dec half life of incretin
b) dec half life of insulin
c) inc half life of insulin
d) inc half life of glucagon
e) dec half life of glucagon
f) inc half life of incretin
f) inc incretin half life, stays active for longer
T/F: Metformin & DPP-4 inhibition has the same effect on whole-body glucose homeostasis
FALSE:
Metformin (MET)= anti-diabetic drug, suppresses hepatic glucose production, maintains HbA1c,
BUT adding a DPP-4 inhibitor lowers overall HbA1c levels.
- those who took DPP-4 inhibition in addition to metformin experienced a significant improvement in whole-body glucose homeostasis
MET & DPP-4 = ______ effects on whole body glucose homeostasis
a) worsened
b) improved
c) opposite
improvement
High levels of GLP-1 causing more severe adverse effects are a result of:
a) incretin mimetics
b) incretin enhancers
a) mimetics
True or false: GLP-levels achieved with insulin enhancers cause an increase in insulin secretion, dec glucagon secretion and overall dec in plasma glucose
true
True or false: GLP-levels achieved with insulin mimetics cause a dec in appetite and food intake as well as adverse effects such as diarrhoea, nausea, abdominal pain
True
higher plasma GLP-1 concentrations associated with GLP-1 levels achieved with _____; GLP-1 levels achieved with __________ do also inc, but not as much (at relatively safe levels)
mimetics; enhancers
A lifestyle modification will _____ body weight and is ________ when with an incretin mimetic therefore ______ reduction
a) lower; not additive; similar
b) lower; additive; greater
c) higher; additive; greater
d) higher; not additive; similar
e) lower; additive; smaller
f) higher; additive;smaller
b) lower; additive; greater
SCFAS produced by gut bacteria influence the production of incretins, providing a partial explanation for the _______ in insulin seen in gut-bacteria (conventionalized) mice.
increase
Gut-bacteria mice had an increase level of fasted insulin and glucose when compared to germ-free, is this increase related to incretin changes? Explain the study that shows this
all mice had gut bacteria, some were GPR41-/- and some were GPR43-/- ( these are what SCFAs signal through)
WT mice active GLP-1»_space;> KO mice
Both GPR41 and 43 -/- mice had lower insulin levels and higher glucose levels in the blood.
* SCFAs produced by gut bacteria have a role (via GPR41/43) in the regulation of blood insulin levels by influencing intestinal incretin release
