The importance of low blood glucose in the development of fetal sheep pancreatic endocrine cells transplanted into athymic mice. 1996

B E Tuch, and F M Petchell, and P Swierkowski
Department of Endocrinology, Diabetes and Metabolism, The Prince of Wales Hospital, School of Anatomy, The University of New South Wales, Sydney, Australia.

The major problem in using fetal sheep pancreas as a transplantable source of insulin-producing cells to reverse diabetes is that beta cells do not differentiate well. Glucotoxicity is a potential explanation for this because the blood glucose level of recipient mice is higher than that of fetal sheep (7 vs. 1.5 mM). To test the effect of approximating these fetal conditions blood glucose levels of recipient athymic mice were lowered for 4 weeks from 7.3 +/- 1.6 mM to a nadir of 3.7 +/- 1.7 mM by administration of insulin pellets. This resulted in a 2.7-fold increase in the percentage of beta cells and a 5.9-fold increase in the number of glucagon-containing alpha cells. The increase in endocrine cells was probably due to improved formation from undifferentiated cells, but greater proliferation of the mature cells is also a possibility. The effect was transient with endocrine cell numbers diminishing once the effect of insulin administration ceased. It is concluded that while transplanted fetal sheep pancreas may not be suitable for reversal of diabetes, it is a useful model for studying how pancreatic endocrine cells develop.

UI MeSH Term Description Entries
D007003 Hypoglycemia A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH. Fasting Hypoglycemia,Postabsorptive Hypoglycemia,Postprandial Hypoglycemia,Reactive Hypoglycemia,Hypoglycemia, Fasting,Hypoglycemia, Postabsorptive,Hypoglycemia, Postprandial,Hypoglycemia, Reactive
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D014183 Transplantation, Heterologous Transplantation between animals of different species. Xenotransplantation,Heterograft Transplantation,Heterografting,Heterologous Transplantation,Xenograft Transplantation,Xenografting,Transplantation, Heterograft,Transplantation, Xenograft
D016332 Fetal Tissue Transplantation Transference of fetal tissue between individuals of the same species or between individuals of different species. Grafting, Fetal Tissue,Transplantation, Fetal Tissue,Fetal Tissue Donation,Donation, Fetal Tissue,Donations, Fetal Tissue,Fetal Tissue Donations,Fetal Tissue Grafting,Fetal Tissue Graftings,Fetal Tissue Transplantations,Graftings, Fetal Tissue,Tissue Donation, Fetal,Tissue Donations, Fetal,Tissue Grafting, Fetal,Tissue Graftings, Fetal,Tissue Transplantation, Fetal,Tissue Transplantations, Fetal,Transplantations, Fetal Tissue
D016381 Islets of Langerhans Transplantation The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species. Grafting, Islets of Langerhans,Pancreatic Islets Transplantation,Transplantation, Islets of Langerhans,Transplantation, Pancreatic Islets,Islands of Langerhans Transplantation,Islands of Pancreas Transplantation,Islet Transplantation,Transplantation, Islands of Langerhans,Transplantation, Islands of Pancreas,Transplantation, Islet,Islet Transplantations,Islets Transplantation, Pancreatic,Transplantations, Islet

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