Glucagon Signaling in the Liver Image from Hædersdal S et al 2018 Mayo Clinic Proceedings 932217239 Glucagon Signaling Primary target sites Liver Purpose to release glucose into the bloodstream ID: 932128
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Slide1
Glycogen Biosynthesis and Metabolism – Part 3
Glucagon Signaling in the Liver
Slide2Image from
Hædersdal
, S., et al (2018) Mayo Clinic Proceedings 93(2):217-239
Slide3Glucagon Signaling
Primary target sites:
Liver – Purpose to release glucose into the bloodstream
Downregulates GlycogenesisDownregulates
Glyco
lysis
(breakdown of glucose/hexoses to make energy)
Upregulates
Glycogen
olysis
(breakdown of glycogen into glucose monomers)
Upregulates
Gluco
neogenesis
(biosynthesis of glucose from organic precursors)
Upregulates
Lipolysis
and
Ketogenesis
Adipose Tissue (in rats, but maybe not in humans??)
Fatty Acid release
Slide4Glucagon Signaling in Liver Cells
Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
Glucagon Hormone
Glucagon Receptor (7TM)
Slide5Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
7TM = G-protein coupled receptor (GPCR)
a
b
g
G-protein
Glucagon Signaling in Liver Cells
Slide6Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
7TM = G-protein coupled receptor (GPCR)
Glucagon Signaling in Liver Cells
Slide7Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
Glucagon Signaling in Liver Cells
Slide8Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
ATP
Adenylyl Cyclase
Glucagon Signaling in Liver Cells
Slide9Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
GTP
ATP
Adenylyl Cyclase
Glucagon Signaling in Liver Cells
Slide10Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GTP
cAMP
GDP
Adenylyl Cyclase
cAMP
cAMP
cAMP
Glucagon Signaling in Liver Cells
Slide11Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
cAMP
GDP
cAMP
cAMP
cAMP
Glucagon Signaling in Liver Cells
Slide12Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Truthortruth
GDP
cAMP
Protein Kinase A
(PKA)
Glucagon Signaling in Liver Cells
cAMP
Slide13Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
cAMP
Protein Kinase A
(PKA)
PKA
Glucagon Signaling in Liver Cells
CREB
Nucleus
Mitochondria
cAMP
Slide14Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
cAMP
Protein Kinase A
(PKA)
PKA
Glucagon Signaling in Liver Cells
CREB
Nucleus
Mitochondria
cAMP
cAMP
Slide15Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
cAMP
Protein Kinase A
(PKA)
PKA
Glucagon Signaling in Liver Cells
CREB
Nucleus
Mitochondria
cAMP
cAMP
Upregulation of Genes
Involved in Gluconeogenesis
Slide16Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
cAMP
Protein Kinase A
(PKA)
PKA
Glucagon Signaling in Liver Cells
Glycolysis
Glycogenesis
Glycogenolysis
Slide17Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
cAMP
PKA
Downregulation of Glycogenesis
Glycogen
Glycogen
Synthase
Glycogen
Synthase
INACTIVE
ACTIVE
PP1
P
P
Slide18Figure modified from
Yan, A., et al (2016) In J
Biol
Sci
12(12):1544-1554
and
Servier
Medical Art
GDP
Downregulation of Glycogenesis
Glycogen
Glycogen
Synthase
Glycogen
Synthase
INACTIVE
ACTIVE
PP1
P
P
cAMP
PKA
PP1
P
P
INACTIVE
Slide19cAMP
PKA
Glycogen
PP1
P
P
Glycogen
PP1
ADP
ATP
LESS ACTIVE
ADP
ATP
PP1
I
P
P
I
INACTIVE
Inhibition of Protein Phosphatase Type 1
Slide20Downregulation of Glycogenesis
Protein Kinase A (PKA) phosphorylates:
Glycogen Synthase and downregulates its activity
Protein Phosphatase Type 1, causing the catalytic domain to dissociate from the regulatory domain = less active PP1An inhibitor of PP1 that binds to the catalytic domain that enables the binding of the inhibitor to the catalytic domain of PP1, effectively inhibiting activity of this phosphatase