Pancreatic hormones, Insulin and glucagon

Question 1

Endocrine pancreas

Answer 1

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

Question 2

Islets

Answer 2

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

Question 3

Blood glucose levels: …

Answer 3

• Blood glucose levels: precisely controlled

within a narrow range

Question 4

High blood glucose

Answer 4

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

Question 5

Main pancreatic hormones controlling blood glucose:

Insulin

Answer 5

• Insulin (lowers blood glucose levels)

Question 6

Main pancreatic hormones controlling blood glucose:

glucagon

Answer 6

• Glucagon (raises blood glucose levels)

Question 7

• Antagonistic hormone pairing:

Answer 7

one hormone activates a process, the other inactivates it;

provides rapid, fine-tuned control

Question 8

Insulin

INS gene

Answer 8

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

Question 9

Insulin

Preproinsulin

Answer 9

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

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

Question 10

Insulin

Proinsulin

Answer 10

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)

Question 11

Insulin

Maturation..

Answer 11

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

Question 12

Insulin

___ stimulated exocytosis
___

Answer 12

Ca2+
-stimulated exocytosis
(subset of granule pool)

Question 13

Insulin

Answer 13

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

Question 14

small amount of
__ escapes cleavage
and is secreted intact

Answer 14

small amount of
proinsulin escapes cleavage
and is secreted intact

Question 15

Basal insulin secretion

Answer 15

(without exogenous

stimuli) takes place in the fasted state

Question 16

Food ingestion

Answer 16

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

Question 17

Primary stimulus for insulin secretion….

Answer 17

rise in blood glucose

Question 18

Insulin secretion

step 1

Answer 18

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

Question 19

Insulin secretion

step 2

Answer 19

Glycolysis and oxidative phosphorylation:

increases ATP:ADP ratio in β cell

Question 20

Insulin secretion

step 3

Answer 20

ATP-dependent K+ channels close

Question 21

Insulin secretion

step 4

Answer 21

β cell depolarizes

Question 22

Insulin secretion

step 5

Answer 22

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

Question 23

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

Answer 23

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.

Question 24

Insulin receptor

Answer 24

• Insulin receptor: a receptor tyrosine kinase

Question 25

Leads to a signal transduction cascade; one effect is | phosphorylation of the ____ glucose transporter

Answer 25

Leads to a signal transduction cascade; one effect is | phosphorylation of the GLUT4 glucose transporter

Question 26

• GLUT4 translocates to the cell surface to facilitate | ___ into that cell

Answer 26

• GLUT4 translocates to the cell surface to facilitate | glucose uptake into that cell

Question 27

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

Answer 27

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

Question 28

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

Answer 28

``` 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 ```

Question 29

MAPK (mitogen-activated protein kinase) Pathways: Active ____ leads to ____ cascade

Answer 29

Active Ras-GTP leads to phosphorylation cascade

Question 30

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) ```

Answer 30

``` • 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) ```

Question 31

• Insulin: promotes ....

Answer 31

• Insulin: promotes nutrient uptake & storage

Question 32

Insulin effects Liver

Answer 32

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

Question 33

Insulin effects Skeletal muscle

Answer 33

promotes glucose uptake | & storage, as well as protein synthesis

Question 34

Insulin effects White adipose tissue:

Answer 34

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

Question 35

____ is processed in a ____ manner, depending on the | dominant PC in ____

Answer 35

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

Question 36

Glucagon

Answer 36

Glucagon: 29-a.a. polypeptide, stored | in vesicles in ⍺ cells

Question 37

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

Answer 37

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

Question 38

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

Answer 38

``` 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 ```

Question 39

Glucagon receptor:___

Answer 39

Glucagon receptor: a GPCR of Gαs class

Question 40

Glucagon receptor Activates _____: produces ____ second messenger, activating ____

Answer 40

• Activates adenylate cyclase: produces | cAMP second messenger, activating PKA

Question 41

Glucagon receptor PKA phosphorylates many key cellular proteins, including ___ regulating ____ _____ • Glucagon receptor signaling also modifies activity of cAMP-responsive transcriptional regulators (___)

Answer 41

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)

Question 42

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

Answer 42

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

Question 43

Glucagon effects | Liver:

Answer 43

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

Question 44

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)

Answer 44

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)