Pre-transplant signal induction for vascularisation in human islets.
Human islet transplant success is partially impaired by slow revascularisation. Our study investigated the potential for rotational cell culture (RC) of human islets combined with thiazolidinedione (TZD) stimulation of peroxisome proliferator-activated receptor gamma (PPARγ) to upregulate vascular endothelial growth factor (VEGF) expression in the islets. Four groups of human islets were studied: static culture (SC) with and without 25 mmol/L TZD and RC with and without 25 mmol/L TZD. These were assessed for insulin secretion and soluble VEGF-A release. Both proteins were quantified by enzyme-linked immunosorbent assay (ELISA), supported with qualitative immunofluorescence staining. RC + TZD increased insulin secretion by >20% (p < 0.05-0.001) in response to 16.7 mmol/L glucose and 16.7 mmol/L glucose + 10 mmol/L theophylline (G + T). This effect was seen at all time intervals compared with SC and without addition of TZD. Soluble VEGF-A release was significantly augmented by RC and TZD exposure with an increased effect of >30% (p < 0.001) at 72 h under both SC and RC conditions. RC supplemented with a TZD enhances and prolongs the release of insulin and soluble VEGF-A by isolated human islets.
Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.
Michelle B
MB
Paget
Hilary E
HE
Murray
Clifford J
CJ
Bailey
Richard
R
Downing
D000328:Adult; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone
Human islets; insulin secretion; revascularisation; rotational culture; thiazolidinedione; vascular endothelial growth factor