Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway:
Gespeichert in:
| Format: | Elektronisch E-Book |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
2013
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| Online-Zugang: | Volltext Volltext Inhaltsverzeichnis |
| Beschreibung: | Aus: PLoS ONE ; 8. 2013 |
| Beschreibung: | 1 Online-Ressource |
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Datensatz im Suchindex
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| adam_text | TABLE OF CONTENTS
LIST OF FIGURES IX
ABBREVIATIONS XI
SUMMARY XIII
ZUSSAMMENFASSUNG XIV
1 .INTRODUCTION 1
1.1 PANCREAS 1
1.1.1 PANCREAS ANATOMY 1
1.1.2 BETA CELL BIOLOGY 2
1.2 PANCREAS REGENERATION 3
1.2.1 TOXIC INJURY 3
1.2.2 SURGICAL INJURY 4
1.3 INCRETIN HORMONES 5
1.3.1 GLUCAGON LIKE PEPTIDE-1 5
1.3.2 ACTIONS OF GLP-1 7
1.3.3 GLP-1 AND F}-CELL PROLIFERATION 8
1.3.4 GLP-1 AND P-CELL NEOGENESIS 9
1.3.5 GLUCAGON LIKE PEPTIDE-1 RECEPTOR 9
1.3.6 GLP-1 INHIBITOR-DIPEPTIDYL PEPTIDASE IV 10
1.3.7 DIPEPTIDYL PEPTIDASE INHIBITOR 11
1.4 DIABETES MELLITUS 11
1.4.1 TYPE 1 DIABETES 11
1.4.2 TYPE 2 DIABETES 12
1.4.3 ISLET TRANSPLANTATION AS A CURE FOR TYPE 1 DIABETES 12
1.4.4 ISLET TRANSPLANTATION AND REGENERATION 12
IV
HTTP://D-NB.INFO/1034044788
1.5 ISLET VASCULATURE 13
1.5.1 THE PANCREATIC ISLET ENDOTHELIAL CELL 14
1.5.2 REVASCULARIZATION OF ISLET GRAFT 15
1.5.3 PROANGIOGENIC FACTORS IN THE REVASCULARIZATION OF ISLET GRAFT 16
1.5.4 ANGIOGENESIS OF ISLET ENGRAFTMENT 16
1.5.5 THE HLF-LA
SYSTEM 17
1.5.6 HIF-IA
INDEPENDENT REGULATION OF VEGF AND ANGIOGENESIS 17
1.5.7 ROLE OF CREB IN ANGIOGENESIS 18
1.5.8 ROLE OF MTOR
AND P70S6KINASE
IN VASCULOGENESIS 18
2. AIM OF THE STUDY 19
3. MATERIALS AND METHODS 20
3.1 MATERIALS 20
3.1.1 CHEMICALS 20
3.1.2 ANTIBODIES 23
3.1.3 KITS 24
3.1.4 HUMAN PRIMER SEQUENCES FOR REALTIME PCR 24
3.1.5 INSTRUMENTS 25
3.1.6 SOFTWARES 25
3.1.7 ANIMALS 26
3.2 METHODS 26
3.2.1 EXPERIMENTAL DESIGN 26
3.2.1.1 PARTIAL PANCREATECTOMY 26
3.2.1.2 EXPERIMENTAL GROUPS 27
3.2.1.3 BLOOD GLUCOSE MEASUREMENT 27
3.2.1.4 BROMO-DE-OXYURIDINE (BRDU) INJECTION 27
V
3.2.1.5 INTRAPERITONEAL GLUCOSE TOLERANCE TEST
(IPGTT) 27
3.2.1.6 PANCREATIC INSULIN CONTENT MEASUREMENT 28
3.2.1.7 INSULIN ELISA 28
3.2.1.8 IMMUNOHISTOCHEMISTRY-LIGHT MICROSCOPY 28
3.2.2 ISLET TRANSPLANTATION 28
3.2.2.1 MOUSE ISLET TRANSPLANTATION 28
3.2.2.2 HUMAN ISLET TRANSPLANTATION 29
3.2.2.3 PORCINE ISLET TRANSPLANTATION 30
3.2.3 INSULIN CONTENT OF ISLET GRAFTS 30
3.2.4 ISLET AREA MEASUREMENT 30
3.2.5 PROLIFERATION OF P-CELLS 31
3.2.6 BLOOD FLOW AND MICROVASCULAR DENSITY 31
3.2.7 MOUSE ISLET ISOLATION AND CULTURE 32
3.2.8 ASSESSMENT OF VEGF SECRETION AND DPP-IV
ACTIVITY 32
3.2.9 EX VIVO ISLET SPROUTING 32
3.2.10 QUANTITATIVE REALTIME PCR IN HUMAN ISLET TRANSPLANT 33
3.2.10.1 RNA ISOLATION 33
3.2.10.2 MEASUREMENT OF RNA CONCENTRATION 33
3.2.10.3 DNASE TREATMENT 34
VI
3.2.10.4 CDNA SYNTHESIS 34
3.2.10.5 REAL TIME PCR ANALYSIS 35
3.2.11 IMMUNOHISTOCHEMISTRY-FLUORESCENT MICROSCOPY 36
3.2.11.1 MEASUREMENT OF VEGF, VEGFR-2, CREB, PCREB, PMTOR
AND P70S6K. EXPRESSION 36
3.2.12 STATISTICAL ANALYSIS 36
4.RESULTS
4.1 SITAGLIPTIN INCREASES PROLIFERATION OF P-CELLS AFTER PANCREATECTOMY
37
4.2 SITAGLIPTIN INCREASES INSULIN AREA AFTER PANCREATECTOMY 38
4.3 SITAGLIPTIN IMPROVES GLUCOSE TOLERANCE IN PANCREATECTOMIZED MICE 38
4.4 DPP-IV CONCENTRATION AND
ACTIVITY REDUCED BY SITAGLIPTIN IN BOTH PLASMA
AND PANCREAS 39
4.5 SITAGLIPTIN ACCELERATES RESTORATION OF NORMAL BLOOD GLUCOSE LEVELS
40
4.6 IMPROVED INSULIN PRODUCTION THROUGH ENHANCED (3 -CELL PROLIFERATION
41
4.7 SITAGLIPTIN IMPROVES VASCULARIZATION 46
4.8 DPP-IV INHIBITION INCREASES FUNCTIONAL BLOOD FLOW TO TRANSPLANTED
ISLETS 47
4.9 SITAGLIPTIN INCREASES VEGF SECRETION IN VITRO 48
4.10 SITAGLIPTIN ENHANCES ISLET ENDOTHELIAL CELL SPROUTING 50
4.11 SITAGLIPTIN IMPROVES SECRETION OF VEGF IN TRANSPLANTED ISLETS 52
4.12 SITAGLIPTIN SENSITIZES VEGFR2 IN TRANSPLANTED ISLETS 53
4.13 SITAGLIPTIN ACTIVATES CREB PATHWAY 53
VII
4.14 SITAGLIPTIN ENHANCES MTOR
AND P70S6K EXPRESSION 55
5.DISCUSSIO
N 56
5.1 SITAGLIPTIN PROMOTES P-CELL PROLIFERATION AND INSULIN AREA IN
PARTIAL
PANCREATECTOMY 56
5.2 THE DPP-IV- GLP-I- VEGF AXIS 57
5.3 POTENTIAL INTRACELLULAR LINKS BETWEEN GLP-1 RECEPTOR ACTIVATION AND
VEGF
SYNTHESIS IN THE P-CELL 58
5.4 GLP-1 RECEPTOR ACTIVATION, CREB PHOSPHORYLATION, MTOR ACTIVATION AND
VEGF
SYNTHESIS IN [3-CELLS BY DPP-IV INHIBITION 59
6.REFERENCE
S 61
7.DECLARATIO
N 69
8.APPENDI
X 70
ACKNOWLEDGEMENTS 71
CURRICULUM VITAE 73
PUBLICATIONS 76
VIII
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| spelling | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway Balaji Samikannu ... 2013 1 Online-Ressource txt rdacontent c rdamedia cr rdacarrier Aus: PLoS ONE ; 8. 2013 Samikannu, Balaji Sonstige (DE-588)1037951247 oth http://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/4200 kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-42003 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027084765&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway |
| title | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway |
| title_auth | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway |
| title_exact_search | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway |
| title_full | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway Balaji Samikannu ... |
| title_fullStr | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway Balaji Samikannu ... |
| title_full_unstemmed | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway Balaji Samikannu ... |
| title_short | Dipeptidyl peptidase IV inhibition activates CREB and improves islet vascularization through VEGF-A/VEGFR-2 signaling pathway |
| title_sort | dipeptidyl peptidase iv inhibition activates creb and improves islet vascularization through vegf a vegfr 2 signaling pathway |
| url | http://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/4200 https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-42003 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027084765&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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