Abstract
Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis. Normal islets cultured with INGAP-PP and VEGFA increased insulin and VEGFA secretion while apoptosis decreased. INGAP-PP-induced effects were prevented by both Rapamycin and SU5416. INGAP-PP effects on β-cell mass and function were significantly associated with a positive effect on islet angiogenesis and VEGFA production/release. VEGF-A possibly potentiates INGAP-PP effect through mTORC pathway.
Keywords:
Angiogenesis; Diabetes; Insulin secretion; Islet cells.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Body Weight / drug effects
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Cell Size / drug effects
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Cytokines / pharmacology*
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DNA / metabolism
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Feeding Behavior / drug effects
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Glucose / pharmacology
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Glucose Tolerance Test
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Indoles / pharmacology
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Insulin / genetics
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Insulin / metabolism
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Insulin-Secreting Cells / cytology
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Insulin-Secreting Cells / drug effects
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Insulin-Secreting Cells / metabolism*
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Integrin beta1 / genetics
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Integrin beta1 / metabolism
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Male
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Neovascularization, Physiologic* / drug effects
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Neovascularization, Physiologic* / genetics
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Peptide Fragments / pharmacology*
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Pyrroles / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats, Wistar
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Vascular Endothelial Growth Factor A / biosynthesis*
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Cytokines
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INGAP peptide
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Indoles
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Insulin
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Integrin beta1
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Peptide Fragments
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Pyrroles
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Semaxinib
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DNA
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Vascular Endothelial Growth Factor Receptor-2
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Glucose