A mouse model of transient diabetes; a new perspective on glucose homeostasis (123.24)
| Autor: | Megan Girtman, Kevin Pavelko, Larry Pease |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:123.24-123.24 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.123.24 |
| Popis: | We have induced acute diabetes following immune attack on the pancreas with islet specific CD8+ T cells, but surprisingly many animals subsequently recovered blood glucose homeostasis. The recovered animals exhibited nearly normal glucose tolerance and produced normal levels of blood insulin following glucose challenge. Remarkably very few islets were present in these animals and those remaining were virtually insulin free. In this model B6 RIP-OVAhi mice receive 100 to 600 naïve OT-1 CD8+ T cells prior to activation by an infection with Theilers murine encephalomyelitis virus encoding the SIINFEKL ovalbumin antigen. When greater numbers of T cells are transferred, this protocol causes acute and fatal diabetes. However, when limiting numbers of T cells are used, animals can recover from the acute phase of the disease. Under these limiting conditions, we find that the mice develop acute pancreatitis by day 5 following infection and stop producing insulin by day 8. By day 11 to 14 some animals begin to recover. Early in the recovery process, insulin positive beta cells are evident in islets. However, late after recovery (days >56) animals that regulate blood sugar normally are found devoid of insulin producing beta cells, though insulin levels are near normal. This raises important questions about how these animals recover glucose homeostasis following cellular immune attack on their islets. Our hypothesis is that insulin is produced outside of the pancreas in these animals. |
| Databáze: | OpenAIRE |
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