title: Persistent reversal of diabetes by transplantation of fetal pig proislets into nude mice.
abstract: Facing the limited availability of human adult and fetal pancreases, fetal pig proislets (pancreatic islet precursors) were investigated in view of several inherent advantages. Six litters of fetuses of mean +/- SE gestational age 75 +/- 3 days were obtained from commercially available farm pigs. Pancreatic tissue was gently digested with collagenase, then a 10-day culture was performed. During culture, fetal proislets showed no insulin response to glucose alone but a significant response to glucose plus theophylline. The insulin content per microgram of DNA in the cultured proislets continuously increased. Histological examination by immunoperoxidase staining showed that, apart from single insulin- and glucagon-positive cells, there were no discrete islets in the pancreatic tissue and the cultured proislets. Diabetes was induced with streptozocin (STZ) in eight nude mice 3-4 wk after proislet transplantation and in another eight nude mice without transplantation. During the initial week, blood glucose levels of mice in both groups increased rapidly. The mean +/- SE peak value of blood glucose levels in the transplanted group was 20.4 +/- 2.0 mM and was 20.1 +/- 1.3 mM in the group without transplantation. Simultaneously, body weight decreased from 29.5 +/- 0.7 to 21.5 +/- 0.9 g and from 27.9 +/- 0.7 to 19 +/- 1 g in the groups, respectively. Afterward, blood glucose levels of mice in the transplanted group gradually decreased, and normoglycemia was achieved in all mice within 50 +/- 13 days after injection of STZ, i.e., 74 +/- 13 days after transplantation. The group without transplantation persistently maintained blood glucose levels greater than 16.7 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medical Clinic and Policlinic, Justus von Liebig University of Giessen, Germany.
authors.forename: X M
authors.initials: XM
authors.lastname: Liu
authors.forename: K F
authors.initials: KF
authors.lastname: Federlin
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
authors.forename: B J
authors.initials: BJ
authors.lastname: Hering
authors.forename: M D
authors.initials: MD
authors.lastname: Brendel
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D016332:Fetal Tissue Transplantation / Q000502:physiology; D005865:Gestational Age; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose