Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endo Repro 1 > Endocrine Pancreas Physio > Flashcards

Endocrine Pancreas Physio Flashcards

1
Q

What does the endocrine pancreas regulate?

A

glucose, fatty acid and amino acid metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What effect does a-adrenergic stimulation have on insulin secretion?

A

decreases insulin secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What effect does Ach stimulation have on insulin secretion?

A

increases insulin secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What do beta cells secrete?

A

insulin and C peptide

they tend to be localized to the central core of the islet, and make up 60-65% of it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do alpha cells secrete?

A

glucagon (inhibits insulin secretion)

they tend to be located near the periphery of the islet, and make up 20% of it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do delta cells secrete?

A

somatostatin
they are interspersed between alpha and beta cells, are neuronal in appearance (send dendrite-like processes to beta cells), and make up 5% of the islet
they facilitate paracrine regulation by stimulating alpha and beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the blood supply to the islet?

A

venous blood from one cell type bathes the other cell types
venous blood from the beta cells carries insulin to the alpha and delta cells
- blood first flows to capillaries in the center of the islet, picking up insulin
- then blood flows to the periphery of the islets, acting on alpha cells to inhibit glucagon secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does insulin stimulate in the islet?

A

alpha cells to secrete glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does glucagon act on?

A

glucagon inhibits beta cells (stopping insulin secretion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does somatostatin act on?

A

somatostatin inhibits both alpha and beta cells (stopping insulin and glucagon release)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the main stimulatory factor of insulin secretion?

A

glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the structure of insulin?

A

1 shorter alpha chain, connected to a longer beta chain via 2 disulfide bridges

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is preproinsulin?

A

a signal peptide, alpha and beta chains with a connecting peptide (C-peptide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is proinsulin?

A

NO signal peptide, C-peptide still attached to insulin
disulfide bridges form in the ER -> packaged in secretory vesicles in the Golgi
proteases cleave the C-peptide, but insulin and C-peptide are still packaged together (secreted in equimolar quantities into the blood)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the relationship between insulin and C-peptide?

A
  • it is a linear (1:1) ratio, so you can get a direct measurement of insulin levels by measuring C-peptide levels
  • C-peptide is excreted unchanged in urine, so it’s used to screen endogenous beta cell function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What effect do sulfonylurea drugs have on pancreatic beta cells?

A
  • they promote the closing of the ATP-dependent K channel, and increase insulin secretion
  • they are used in the treatment of T2DM
    ex: tolbutamide, glyburide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What makes up the ATP-dependent K-channel?

A

Sulfonylurea receptor (SUR) + inward-rectifier K-channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What effect does ATP have on the ATP-dependent K-channels in beta cells?

A

increase in ATP will CLOSE the channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the biphasic manner of insulin secretion?

A

1st phase: immediate release of pre-formed vesicles

2nd phase: occurs at a much more gradual rate, starts about 20 minutes after glucose eating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do GI peptides, local glucagon and somatostatin contribute to insulin release?

A

CCK and ACh bind mAChr -> activating PLC via Gq pathway -> IP3/DAG -> insulin release

Glucagon and GLP-1 activate Gs -> cAMP -> insulin release

Somatostatin binds Gi, inhibiting cAMP = no insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens when insulin binds to it’s receptor, tyrosine kinase?

A
  • tyrosine kinase phosphorylates itself and other proteins
  • the receptor complex is then internalized by its target cell
  • then insulin down-regulates its own receptor (in order to “tone down” its response)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where are the insulin binding sites on the insulin receptor?

A

on the alpha subunits

2 alpha subunits are connected to each other, and to two beta subunits via disulphide bridges

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the downstream signaling cascades when insulin binds its receptor?

A

PI3K and MAP kinase

  • which lead to increased glycogen/lipid/protein synthesis, decreased lipolysis and cell growth/differentiation
24
Q

What are the 4 steps of peripheral glucose uptake?

A
  1. insulin binds its receptor
  2. signal transduction cascase (PI3K-mediated)
  3. exocytosis of vesicles inserts GLUT4 transporters in the membrane
  4. glucose enters cell thru GLUT4
25
Q

What are the major effects of insulin on skeletal muscle?

A
  • increase glucose uptake via GLUT4 transporter -> leads to an increase glycogen synthesis
  • increase in glycolysis, carbohydrate oxdation, lipid synthesis
  • decrease in gluconeogenesis
  • increase in protein synthesis, decrease in protein breakdown
26
Q

What is an alternative intracellular pathway for glucose uptake (independent of insulin)?

A

muscle contractions stimulate the activation of AMP-kinase, resulting in GLUT4 translocation to plasma membrane

**highlights the importance of exercise management for preventing insulin resistance/diabetes

27
Q

What are the effects of insulin on triglyceride and FA metabolism?

A
  • insulin increases uptake of rtiglycerides via lipoprotein lipase
  • insulin increases glucose and FA uptake
  • insulin inhibits hormone sensitive lipase, which converts triglycerides to FA
28
Q

What effect does insulin have on glucose, FA, ketoacid, AA and K blood levels?

A

All will decrease
insulin causes an increase in glucose uptake, increase glycogen formation, increase protein synthesis, increase fat deposition, decrease in lipolysis, increase K uptake into cells

29
Q

What is the effect of insulin on adipose tissue?

A
  • increase glucose uptake
  • increase lipogenesis
  • decrease lipolysis
30
Q

What is the effect of insulin on the liver?

A
  • decrease gluconeogenesis
  • increase glycogen synthesis
  • increase lipogenesis
31
Q

What is the effect of insulin on striated muscle?

A
  • increase glucose uptake
  • increase glycogen synthesis
  • increase protein synthesis
32
Q

How can insulin compensate for hyperkalemia?

A

insulin is important for the uptake of K into cells

in a patient with hyperkalemia, a dose of insulin with glucose can help regulate intracellular K levels

33
Q

What are stimulatory factors of insulin secretion?

A

increase in glucose, AA, FA, ketoacid, glucagon, cortisol. GIP, ACh, K, sulfonylurea drugs, obesity

NOTE: compensatory changes that happen with obesity lead to more insulin secretion to try to regulate glucose

34
Q

What are inhibitory factors of insulin secretion?

A

a decrease in blood glucose, fasting, somatostatin, exercise, a-adrenergic agonists, diazoxide

NOTE: exercise and a-adrenergic stimulation (SNS) are related - exercise will increase SNS stimulation, which leads to adrenergic receptor activation -> thereby inhibiting insulin secretion

35
Q

What is T1DM?

A

autoimmune disease leads to beta cell destruction -> inadequate insulin secretion

NOTE: symptoms not evident until approx 80% of beta cells have been destroyed

36
Q

What are the levels of blood glucose, FA, ketoacid and AA in T1DM?

A
  • increase in blood glucose (decrease uptake of glucose, increase in gluconeogenesis)
  • increase in blood FA and ketoacids (decrease in FA synthesis, increase in triglyceride breakdown, increase in conversion of FA to ketoacids, decreased utilization of ketoacid by tissues) -> results in diabetic ketoacidosis (DKA)
  • increase in blood AA (increased protein breakdown, decreased protein synthesis, increased catabolism of AA (loss of lean body mass), increased ureagenesis
37
Q

What effect does T1DM have on hyperkalemia?

A

shifts K out of the cell
- intracellular K is low, lack of insulin effects Na/K-ATPase

NOTE: even though plasma levels may be normal, total body K is usually below normal due to polyuria and dehydration

38
Q

What effect does T1DM have on osmotic diuresis?

A
  • increased blood glucose results in increased filtered load of glucose, exceeding reabsorption capacity of proximal tubule
  • water and electrolyte reabsorption prevented
  • polyuria: leads to increased excretion of Na and K, even though urine concentration of electrolytes is low -> leads to THIRST
39
Q

What is the first thing to disappear in diabetic individuals?

A

the first-phase (acute phase) of insulin response

40
Q

What is the objective of insulin replacement therapy for T1DM?

A

to recreate normal physiology, of basal and bolus insulin levels

41
Q

What are the drawbacks of insulin replacement therapy/

A
  • painful, time consuming
  • lag between glucose measurement and insulin dosing
  • delayed absorption of insulin following subcutaneous injection
  • poor blood glucose control -> leading to periods of hyper glycemia
42
Q

What is T2DM?

A
  • progressive exhaustion of active beta cells leads to insulin resistance (95% of diabetes cases!)
  • patients are able to make insulin, but become resistant
  • will show normal or elevated levels on insulin initially, but then levels will decrease as beta cells begin to fail (hyperinsulinemia -> hypoinsulinemia)

NOTE: resistance happens in phases, over time

43
Q

What are the 3 causes for obesity-induced insulin resistance?

A
  1. GLUT4 uptake of glucose in response to insulin release
  2. decreased ability of insulin to repress hepatic glucose production
  3. inability of insulin to repress hormone-sensitive lipase (HSL) or increase lipoprotein lipase (LPL) in adipose tissue
44
Q

How do you treat T2DM?

A
  • caloric restriction and weight reduction
  • insulin secretagogues: sulfonylurea drugs, incretin analog of GLP-1 (exenatide) injection
  • slow absorption of carbohydrates
  • insulin sensitizers (metformin, upregulates insulin receptors on target tissues)
45
Q

What is the glucose tolerance test:

A
  1. normal subject receiving oral glucose: insulin levels will spike really high after eating glucose (150), glucose level stays below 150, resting glucose level under 100
  2. normal subject receiving IV glucose: insulin levels show bi-phasic peaks, one immediately after glucose administration, and the second one more gradual, but the glucose peak is suuuper high (350+), while the insulin peak stays under (100)
  3. diabetic subject receiving oral glucose: glucose level shows a large increase (275), followed by a gradual decrease back to resting level (which is higher than in normal subject at 150), insulin level never spikes, just rises gradually until it stops (has no effect on glucose levels)
46
Q

What are incretin hormones?

A
  • intestine derived hormones: GLP-1, GIP
  • secreted in response to GI glucose and fat
  • stimulate insulin secretion (glucose dependent)
  • inhibit glucagon secretion
  • slow gastric emptying
47
Q

What change does T2DM have on the normal incretin effect?

A

in healthy patients, the normal incretin effect is significant: showing a big difference in insulin levels when comparing oral glucose (causes large spike in insulin levels) and IV glucose infusion (small spike)

in T2DM patients, the incretin effect is drastically reduced, showing much less of a change in oral versus IV glucose levels

48
Q

What are some associated conditions of T1DM?

A

autoimmune thyroid disease, celiac disease, Addison’s disease

49
Q

What are some associated conditions of T2DM?

A

obesity, lipid abnormalities, polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD)

50
Q

What is glucagon?

A

single straight-chain polypeptide with 29 AA’s
member of a family of peptide that includes GI hormones secretin and GIP
synthesized as preproglucagon
stored in dense granules until alpha cells are stimulated

51
Q

What is the major stimulatory factor of glucagon secretion?

A 
decrease in blood glucose levels
increase in arginine or alanine
fasting
CCK
B-adrenergic receptors
ACh
52
Q

What inhibits the synthesis and secretion of glucagon?

A

insulin and somatostatin, as well as an increase in FA and ketoacid concentration

53
Q

What are the major actions of glucagon on the liver?

A

to increase blood glucose by:

  • increasing glucogenolysis and inhibiting glycogen formation from glucose
  • increasing gluconeogenesis by decreasing production of fructose-2,6-biphosphate
54
Q

What are the effects of glucagon on glucose, Fa and ketoacid levels in the blood?

A

all will increase

NOTE: glucagon will increase lipolysis and inhibit FA synthesis, which shunts substrates toward gluconeogenesis. ketoacids are then produced from FA’s

55
Q

What are the stimulatory factors affecting glucagon secretion?

A

fasting, decrease in glucose, increase in AA’s (especially arginine), increase in FA and ketoacids, CCK, B-adrenergic agonists, ACh

56
Q

What are the inhibitory factors affecting glucagon secretion?

A

insulin, somatostatin, increase in FA and ketoacids

57
Q

What are the actions of glucagon?

A

increase glycogenolysis (increases blood glucose)
increase gluconeogenesis
increase lipolysis (increases blood FA)
increase ketoacid formation (increases blood ketoacids)

Endo Repro 1 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions