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Normalization of glucose post-transplantation into diabetic rats of pig pancreatic primordia preserved in vitro.

ABSTRACT: Embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of non-immunosuppresed steptozotocin (STZ)-diabetic Lewis rats normalize levels of circulating glucose within 2-4 weeks. Exocrine tissue does not differentiate after transplantation of pancreatic primordia. Rather individual endocrine (beta) cells engraft within the mesentery.To determine whether transplanted pig pancreatic primordia engraft, differentiate and function in rat hosts after preservation in vitro, we implanted pig pancreatic primordia into STZ-diabetic rats either directly or after 24 hours of suspension in ice-cold University of Wisconsin (UW) preservation solution with added growth factors. Here we show engraftment in mesentery and mesenteric lymph nodes and normalization of glucose levels in STZ-diabetic rat hosts following transplantation of preserved E28 pig pancreatic primordia comparable to glucose normalization after transplantation of non-preserved E28 pancreatic primordia.

SUBMITTER: Rogers SA

PROVIDER: S-EPMC2634179 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Normalization of glucose post-transplantation into diabetic rats of pig pancreatic primordia preserved in vitro.

Rogers Sharon A SA Hammerman Marc R MR

Organogenesis 20080101 1

Embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of non-immunosuppresed steptozotocin (STZ)-diabetic Lewis rats normalize levels of circulating glucose within 2-4 weeks. Exocrine tissue does not differentiate after transplantation of pancreatic primordia. Rather individual endocrine (beta) cells engraft within the mesentery.To determine whether transplanted pig pancreatic primordia engraft, differentiate and function in rat hosts after preservation in vitro, we ...[more]

PMID: 19279715

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Project description:AimDiabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status.MethodsWe used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant.ResultsAll analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD.InterpretationContinuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.

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Normalization of glucose post-transplantation into diabetic rats of pig pancreatic primordia preserved in vitro.

Publications

Normalization of glucose post-transplantation into diabetic rats of pig pancreatic primordia preserved in vitro.

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