GLP-1 receptor signaling protects pancreatic beta cells in intraportal islet transplant by inhibiting apoptosis.
To clarify the cytoprotective effect of glucagon-like peptide-1 receptor (GLP-1R) signaling in conditions of glucose toxicity in vivo, we performed murine isogenic islet transplantation with and without exendin-4 treatment. When a suboptimal number of islets (150) were transplanted into streptozotocin-induced diabetic mice, exendin-4 treatment contributed to the restoration of normoglycemia. When 50 islets expressing enhanced green fluorescent protein (EGFP) were transplanted, exendin-4 treatment reversed loss of both the number and mass of islet grafts one and 3 days after transplantation. TUNEL staining revealed that exendin-4 treatment reduced the number of apoptotic beta cells during the early posttransplant phase, indicating that GLP-1R signaling exerts its cytoprotective effect on pancreatic beta cells by inhibiting their apoptosis. This beneficial effect might be used both to ameliorate type 2 diabetes and to improve engraftment rates in clinical islet transplantation.
Toyoda
Kentaro
K
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
Okitsu
Teru
T
Yamane
Shunsuke
S
Uonaga
Taeko
T
Liu
Xibao
X
Harada
Norio
N
Uemoto
Shinji
S
Seino
Yutaka
Y
Inagaki
Nobuya
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage*
D010455:Peptides; D014688:Venoms; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide