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Biol 432 > Pancreatic hormones, Insulin and glucagon > Flashcards

Pancreatic hormones, Insulin and glucagon Flashcards

1
Q

Endocrine pancreas

A 
Islets of Langerhans,
made up of 5 different cell types; each
produces insulin, glucagon, somatostatin,
pancreatic polypeptide, or ghrelin
(all are peptide hormones)
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2
Q

Islets

A 
• Islets: richly vascularized (5-10X blood flow
compared to exocrine tissue);
innervated by sympathetic,
parasympathetic, and sensory neurons,
and surrounded by astroglial cells
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3
Q

Blood glucose levels: …

A

• Blood glucose levels: precisely controlled

within a narrow range

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4
Q

High blood glucose

A

(hyperglycemia) – affects osmotic
balance of blood, and causes long-term damage to
organs and tissues

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5
Q

Main pancreatic hormones controlling blood glucose:

Insulin

A

• Insulin (lowers blood glucose levels)

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6
Q

Main pancreatic hormones controlling blood glucose:

glucagon

A

• Glucagon (raises blood glucose levels)

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7
Q

• Antagonistic hormone pairing:

A

one hormone activates a process, the other inactivates it;

provides rapid, fine-tuned control

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8
Q

Insulin

INS gene

A

INS gene expressed due to
unique set of transcription
factors in β cells

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9
Q

Insulin

Preproinsulin

A 
Preproinsulin: Signal
peptide is cleaved almost
immediately after
translation in ER,
producing proinsulin
(folded, disulphide bonds)

: 110-a.a.,
biologically inactive.
In ER.

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10
Q

Insulin

Proinsulin

A 
Proinsulin: transported to
Golgi apparatus (further
post
-translational
modifications); packaged
into secretory granules
86-a.a.,
biologically inactive.
• In ER: folding,
disulphide bonds
• In Golgi apparatus: further
modifications (glycosylation)
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11
Q

Insulin

Maturation..

A 
Maturation” of secretory
granules (proinsulin
cleavage and changes to
pH & contents that cause
insulin crystallization
)
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12
Q

Insulin

___ stimulated exocytosis
___

A

Ca2+
-stimulated exocytosis
(subset of granule pool)

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13
Q

Insulin

A

51-a.a.,
biologically active as monomer.
In secretory granules.

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14
Q

small amount of
__ escapes cleavage
and is secreted intact

A

small amount of
proinsulin escapes cleavage
and is secreted intact

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15
Q

Basal insulin secretion

A

(without exogenous

stimuli) takes place in the fasted state

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16
Q

Food ingestion

A

Food ingestion: leads to rise in insulin levels
within 8-10 minutes (2 phases/peaks of insulin
if stimulus persists); decline to basal levels by
90-120 minutes after meal

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17
Q

Primary stimulus for insulin secretion….

A

rise in blood glucose

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18
Q

Insulin secretion

step 1

A

β cell senses glucose levels via its
metabolism. Glucose enters β cell
transported by GLUT glucose transporters

19
Q

Insulin secretion

step 2

A

Glycolysis and oxidative phosphorylation:

increases ATP:ADP ratio in β cell

20
Q

Insulin secretion

step 3

A

ATP-dependent K+ channels close

21
Q

Insulin secretion

step 4

A

β cell depolarizes

22
Q

Insulin secretion

step 5

A

This activates voltage-gated Ca2+ channels,
allowing an influx of Ca2+ that stimulates
exocytosis of insulin-containing granules)

23
Q

Primary stimulus for insulin secretion:
rise in blood glucose; but other factors also have
effects…..

A

Primary stimulus for insulin secretion:
rise in blood glucose; but other factors also have
effects – e.g., GLP-1 & other gastrointestinal
hormones; some amino acids, neural inputs, etc.

24
Q

Insulin receptor

A

• Insulin receptor: a receptor tyrosine kinase

25
Q

Leads to a signal transduction cascade; one effect is

phosphorylation of the ____ glucose transporter

A

Leads to a signal transduction cascade; one effect is

phosphorylation of the GLUT4 glucose transporter

26
Q

• GLUT4 translocates to the cell surface to facilitate

___ into that cell

A

• GLUT4 translocates to the cell surface to facilitate

glucose uptake into that cell

27
Q

PI3K (phosphatidylinositol
3-kinase)-Akt/PKB Pathway:

PI3K

A

generates 2nd
messenger
PI(3,4,5)P3

28
Q

PI3K (phosphatidylinositol
3-kinase)-Akt/PKB Pathway:

This eventually leads
to recruitment &
activation of \_\_\_, an
important effector
that \_\_\_\_
many cellular
proteins, including
\_\_\_\_
(not shown here)

In general: ____
uptake; __, ___ and ___
synthesis/storage;
gene expression

A 
This eventually leads
to recruitment &
activation of Akt, an
important effector
that phosphorylates
many cellular
proteins, including
transcription factors
(not shown here)
In general: glucose
uptake; glycogen,
protein, & lipid
synthesis/storage;
gene expression
29
Q

MAPK (mitogen-activated
protein kinase) Pathways:

Active ____ leads to
____
cascade

A

Active Ras-GTP leads to
phosphorylation
cascade

30
Q

MAPK (mitogen-activated
protein kinase) Pathways:

• MAPK is \_\_\_\_
activated in the
cascade; it is an
important effector that \_\_\_\_ many
cellular proteins, and
also\_\_\_\_ to the
nucleus where it
\_\_\_\_ transcription factors
In general: effects on
\_\_\_\_ &
\_\_\_ , and
gene expression
(also cross-talk with
other pathways)
A 
• MAPK is kinase
activated in the
cascade; it is an
important effector that
phosphorylates many
cellular proteins, and
also translocates to the
nucleus where it
phosphorylates
transcription factors
In general: effects on
cell growth &
differentiation, and
gene expression
(also cross-talk with
other pathways)
31
Q

• Insulin: promotes ….

A

• Insulin: promotes nutrient uptake & storage

32
Q

Insulin effects

Liver

A

Liver: promotes glucose storage
(as glycogen);
while inhibiting synthesis/release of glucose

33
Q

Insulin effects

Skeletal muscle

A

promotes glucose uptake

& storage, as well as protein synthesis

34
Q

Insulin effects

White adipose tissue:

A

: promotes glucose
uptake and facilitates fatty acid uptake
(together, promoting storage of nutrients as
triglycerides);
while inhibiting mobilization of stored lipids

35
Q

____ is processed in a ____ manner, depending on the

dominant PC in ____

A

Proglucagon is processed in a tissuespecific manner, depending on the
dominant PC in secretory vesicles

36
Q

Glucagon

A

Glucagon: 29-a.a. polypeptide, stored

in vesicles in ⍺ cells

37
Q

Glucagon : Secreted when blood glucose is ___; also in response to prolonged ___, ___, and protein-rich meals

A

Glucagon Secreted when blood glucose is low;
also in response to prolonged fasting,
exercise, and protein-rich meals

38
Q

Glucagon Mechananism not clear. Partly due to
___-intrinsic glucose sensing
when glucose is ___; also, both ___ (from β cells) and
___ (from δ cells) inhibit glucagon secretion when their levels are ___ (___ glucose); also
affected by other hormones &
neural inputs

A 
Mechanism not clear. Partly due to
α-cell-intrinsic glucose sensing
when glucose is low; also, both
insulin (from β cells) and
somatostatin (from δ cells) inhibit
glucagon secretion when their
levels are high (high glucose); also
affected by other hormones &
neural inputs
39
Q

Glucagon receptor:___

A

Glucagon receptor: a GPCR of Gαs class

40
Q

Glucagon receptor

Activates _____: produces
____ second messenger, activating ____

A

• Activates adenylate cyclase: produces

cAMP second messenger, activating PKA

41
Q

Glucagon receptor

PKA phosphorylates many key cellular proteins, including ___ regulating ____ _____

• Glucagon receptor signaling also modifies activity of cAMP-responsive transcriptional regulators (___)

A

PKA phosphorylates many key cellular proteins, including enzymes regulating nutrient metabolism

• Glucagon receptor signaling also modifies activity of cAMP-responsive transcriptional regulators (effects on gene expression)

42
Q

Glucagon: promotes delivery of energy from the liver to the other tissues between meals

A

Glucagon: promotes delivery of energy
from the liver to the other tissues
between meals

43
Q

Glucagon effects

Liver:

A

Liver: major target organ for glucagon, where it stimulates breakdown of glycogen (stored glucose), and
production of glucose & ketone bodies

44
Q

Exercise
__ GH (also testosterone) ____ cortisol (glucocorticoid) and epinephrine & norepinephrine (catecholamines)
…cortisol & epinephrine are key regulators of the
stress response, causing ____ blood glucose (also: ___ insulin, ____ glucagon)

A

Increased GH (also testosterone)
• Increased cortisol (glucocorticoid) and
epinephrine & norepinephrine (catecholamines)
…cortisol & epinephrine are key regulators of the
stress response, causing ↑ blood glucose
(also: decreased insulin, increased glucagon)

Biol 432 (8 decks)

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