Week 4: Endocrine pancreas Flashcards

(56 cards)

1
Q

Exocrine pancreatic cells

A

Acinar cells (digestive enzymes)

Duct cells (HCO3-)

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2
Q

Endocrine pancreatic cells

A

Islets of langerhans

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3
Q

Identify structures and functions

A
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4
Q

Identify histology of islets of Langerhans histology cartoon

A
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5
Q

Insulin function

A

tells cells to take up glucose (such as skeletal muscle through GLUT 4)

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6
Q

Insulin counter hormone

A

Glucagon

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7
Q

Insulin secreted by

A

β cells of the pancreas

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8
Q

What is the normal fasting range of glucose?

A

70-110 mg/dL

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9
Q

What secretes somatostatin?

A

D cells of the pancreas

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10
Q

What secretes glucagon?

A

α-cells of the pancreas

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11
Q

Explain what is happening here

A
  • fasting level of glucose goes up after a meal to around 130 or 140 mg/dL and it slowly declines back to basal levels due to glucose going into cells where it is utilized or stored.
  • Insulin is secreted by β cells of the pancreas in response to the rise in glucose levels in the blood after a meal
  • Insulin never drops to 0 it always is there even in the fasting state
  • Glucagon is high during the fasting state and it spikes but then goes way down to basal levels after a meal
  • After fasting for a while glucagon levels will rise to fed state levels
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12
Q

Insulin and glucose are?

A

counter-hormones secreted by the pancreas

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13
Q

What happens when blood glucose level is high to the pancreatic hormones

A
  • after a meal the β cells of the pancreas respond to high glucose levels and secrete insulin
  • α- cells respond to the high glucose levels and stop secreting glucagon
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14
Q

what is in the center of the islet of langerhans?

A

β-cells

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15
Q

Describe the blood supply of the islet of Langerhans

A

there is a central artery so the β-cells respond first because they are in the center of the islet

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16
Q

How is pancreatic secretion regulated

A
  • paracrine regulation
  • Insulin inhibits secretion of glucagon from the α cells
  • This all has to do with the architecture of the islet of Langerhans
  • So the β cells actually control insulin and glucagon levels
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17
Q

Describe what happens in the fasting state

A

low blood glucose slows insulin secretion which stops inhibiting glucagon so the α cells can start secreting glucagon again

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18
Q

Catabolic state hormone

A

Glucagon

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19
Q

Anabolic state hormone

A

Insulin

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20
Q

Identify the mechanism of insulin synthesis

A
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21
Q

Describe the synthesis of insulin

A
  • mRNA from Preproinsulin gene
  • Synthesis of preproinsulin (excision of the signal peptide and a disulfide bond is formed)
  • Transport of proinsulin to the Golgi where it is cleaved into insulin and is packaged into vesicles
  • Mature insulin is ready for signaling in storage vesicles
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22
Q

Describe the molecular structure of insulin

A
  • 2 disulfide bonds
  • cleavage of the proform of proinsulin (2 endoproteases) releases the mature insulin which is the A chain and the B chain which is held together by a disulfide bond
  • The disulfide-linked A and B chain is the mature form of insulin
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23
Q

How do β cells sense glucose?

A
  • in the β cell, GLUT 2 glucose transporter facing the blood
  • Glucose enters
  • oxidized through glycolysis, TCA cycle and electron transport
  • Creating a high ATP>/>ADP ratio
  • ATP dependent K+ channel (normally allows the passage of K+ outside the cell) When ATP binds to the channel, it is inhibited from transporting so a + charge builds in the β cell
  • There is a voltage-gated Ca2+ channel which responds to the difference in charge and lets Ca2+ into the cell
  • The Ca2+ activates transport of insulin storage vesicles to the membrane to let insulin into the blood
24
Q

What are Sulfonylurea drugs?

A

They target β cells ATP dependent K+ channels and act like ATP

It mimics the glucose-sensing system of the β cells to get insulin into the circulation

25
What is the primary organ responsible for reducing plasma glucose levels
Skeletal muscle
26
Describe insulin action on skeletal muscle
* insulin binds to Tyrosine kinase receptor on skeletal muscle membranes and activates it, the tyrosine kinase portion autophosphorylates the Tyrosine kinase receptor cytoplasmic portion of the dimer which phosphorylates the other side * The Activated insulin receptor phosphorylates and activates IRS-1 which activates the AKT pathway * AKT pathway translocates the cytoplasmic GLUT 4 vesicles to the membrane to allow glucose into the skeletal muscle cells * Plasma Glucose can now enter through GLUT 4
27
What is the main defect in insulin resistance?
Insulin receptor can be activated but the activation of IRS-1 is broken
28
How do skeletal muscles respond to the fasting state
the ligan insulin is no longer present so the tyrosine kinase insulin receptor is no longer activated which no longer activated IRS-1 which no longer activates the AKT pathway and so skeletal muscle endocytoses the GLUT 4 transportes back into cytoplasmic receptors If this did not happen blood glucose levels would continue to drop and could cause death
29
GLUT 4 affinity
High affinity
30
Describe GLUT 2 vs GLUT 4 kinetics
The differing affinity and transport activity of the various GLUT transporters allow for targeted transport of glucose GLUT 1, GLUT 3, and GLUT 4 are high-affinity glucose transporters GLUT 2 will only work when there are high levels of glucose because of its low affinity
31
1/2 Vmax =
Km
32
GLUT 1 expression and function
33
GLUT 2 expression and function
34
GLUT 3 expression and function
35
GLUT 4 expression and function
36
GLUT 5 expression and function
37
Glucagon molecular structure
38
What is the fructose transporter
GLUT 5
39
What are the insulin-responsive glucose transporters
GLUT 4 is the only insulin-responsive glucose transporter
40
Describe the glucagon signaling pathway
Glucagon binds to its receptor which is a heterotrimeric gαs protein receptor activates adenylate cyclase and increases cAMP and activates PKA which phosphorylates a bunch of regulators and effectors (lots of enzymes) an enormous shift in metabolic pathways
41
What kind of hormone is insulin?
peptide hormone
42
What kind of hormone is glucagon?
Peptide hormone
43
Insulin effects on Fatty acid uptake and release in adipose
Stimulates the synthesis of triglycerides (TG) from free fatty acids (FFA) Inhibits the release of FFA from TG
44
Glucagon effects on Fatty acid uptake and release in adipose
stimulates release of FFA from TG
45
Insulin effects on the liver
increases glucose uptake and synthesis of glycogen
46
Glucagon effects on the liver glycogen
stimulates glycogenolysis and glucose release
47
Insulin effects on gluconeogenesis in the liver
inhibits and saves amino acids
48
Glucagon effects on gluconeogenesis in the liver
* Stimulates gluconeogenesis * glucose is synthesized and release
49
Insulin effects on glucose uptake in skeletal muscle
stimulates glucose uptake by locating GLUT 4 to the membrane
50
Glucagon effects on glucose uptake in skeletal muscle
no receptors so there is no effect
51
Insulin effects on skeletal muscle glycogen
stimulates glycogenesis
52
Glucagon effects on skeletal muscle glycogen
no receptor so no effects
53
Insulin effects on amino acid uptake
stimulates uptake to increase protein synthesis
54
Glucagon effects on amino acid uptake
no receptor so no effect
55
Insulin effects on the brain
reduces hunger
56
Glucagon effects on the brain
no effect