Peter Dempsey PhD

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Growth Factor Signals involved in Beta Cell
Survival and Regeneration Role of ErbB
Receptor Signaling
Peter Dempsey PhD Associate Professor Dept. of
Pediatrics and Molecular Integrative
Physiology Brehm Scientist, Michigan
Comprehensive Diabetes Center
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Beta Cell Mass is Dynamically Regulated to
Maintain Glucose Homeostasis
Islet
Beta cells make up 1 of pancreatic mass
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Potential Sources of New Beta Cells
3. Differentiation from pancreatic progenitors
neogenesis
1. Differentiation from ES cells
.
2. Proliferation of existing ? cells
regeneration
4. Transdifferentiation
e.g. Exocrine cells Hepatocytes
Enteroendocrine cells
?-cells for transplantation
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Mouse Models of ErbB Receptor Signaling in the
Pancreas
Cell Surface
ErbB4
ErbB1
?-secretase
ADAM17
ADAM10
Cytoplasm
Remnant
4ICD
Gain-of-Function Studies
Loss-of-Function Studies
ErbB Ligands Betacellulin - Doxycycline-regulated
bitransgenic PDX-tTA
TRE2-BTCHA
Cre Drivers PDX-Cre Pancreas-specific RIP-Cre
Beta cell-specific
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BTC-Deficient mice have Reduced Insulin Staining
and Impaired Glucose Tolerance
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Generation of Doxycycline-Regulated BTC
Transgenic Mice.
Bitransgenic Pdx-tTA/pTRE2 BTCHA mice express
full-length BTCHA precursor.
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BTC Overexpression in Beta Cells Increases
Insulin Staining and Improves Beta Cell Function
Pdx-tTA
Bitransgenic
- increased insulin nuclear PDX-1 staining
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Models of Beta Cell Stress In Vivo

• 60 partial pancreatectomy
• low-dose streptozotocin
• high fat diet

New Model of Beta Cell Neogenesis Regeneration
In Vivo

• RIP-DTR transgenics (Herrera, unpublished)

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Acknowledgments
Dempsey lab (UM) Post-docs Alex Stoeck Wenbo
Yan Res. Technicians Patty Gillispie Li
Shang Work-Study Students Fei Chen Farah
Daneshvar Grace Park Jason Rizqallah
Roy Black (Amgen) Yuval Dor (Jerusalem) Pedro
Herrera (Geneva) Jan Jensen (Cleveland) Al
Powers (Vanderbilt) Chris Rhodes (Chicago)
Funding JDRF, NIH, MDRTC
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Pathways of islet-subtype specification
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Over-Expression of DN ErbB1 causes Hyperglycemia
and decreased Beta Cell Mass
PDX-DN ErbB1 transgenic
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Acknowledgments
Dempsey lab (UM) Post-docs Alex Stoeck Wenbo
Yan Res. Technicians Patty Gillispie Li
Shang Work-Study Students Fei Chen Farah
Daneshvar Grace Park Jason Rizqallah
Roy Black (Amgen) Pedro Herrera (Geneva) Jan
Jensen (Cleveland) Tom Jetton (Vermont) Al
Powers (Vanderbilt) Chris Rhodes lab
(Chicago)