Development of islet-like cell clusters after pancreas transplantation in the spontaneously diabetic Torri rat.
Pancreas transplantation (PTx) has evolved as a clinical therapy to achieve sustained euglycemia. However, it remains unclear if naive diseased islets of the pancreas benefit from the avoidance of glucose toxicity by PTx. In the present study, using an animal model of type 2 diabetes, the Spontaneously Diabetic Torii (SDT; RT1a) rat, we syngeneically transplanted nondiabetic 10-week-old pancreaticduodenal grafts into diabetic 25-week-old recipients. In the control SDT rats that received no treatment, hyperglycemia developed with a mean onset time of 25 +/- 3.9 weeks of age. Few normal islet cells were found from 25 weeks and none at 40 weeks. However, in the PTx rats, the onset age (graft age) of diabetes was significantly prolonged (47 +/- 18.2 weeks). Moreover, we found that the beta-cell mass was significantly increased in the naive pancreases of 40-week-old PTx recipients (PTx40-naive). Interestingly, islet-like cell clusters of varying size were found close to ductal structures of PTx40-naive pancreases, suggesting that these cells are derived from ductal cells. Furthermore, pancreatic and duodenal homeobox factor-1 (PDX-1) was more clearly expressed in the nuclei of PTx40-naive pancreatic islet-like cell clusters. Our results demonstrate the development of duct-derived beta cells in the pancreas of type 2 diabetic recipients after PTx.
Miao
Gang
G
Department of Surgery (E1), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ito
Toshinori
T
Uchikoshi
Fumihiro
F
Tanemura
Masahiro
M
Kawamoto
Koichi
K
Shimada
Kazunori
K
Nozawa
Masumi
M
Matsuda
Hikaru
H
D017668:Age of Onset; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D005934:Glucagon / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology / Q000633:toxicity; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007328:Insulin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D016035:Pancreas Transplantation / Q000379:methods* / Q000473:pathology*; D051381:Rats; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis
D018398:Homeodomain Proteins; D007328:Insulin; D019394:Ki-67 Antigen; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon; D005947:Glucose