1986 Fiscal Year Final Research Report Summary
Immunologic process of diabetes induced by sub-dose of streptozotocin.
| Project/Area Number |
60571047
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tokushima |
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Principal Investigator |
KAWADA Jun University of Tokushima, Professor, 薬学部, 教授 (10035537)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Mikio University of Tokushima, AssociateProfessor, 薬学部, 助教授 (10035561)
KOBAYASHI Shigeru University of Tokushima, Professor, 薬学部, 教授 (70035533)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Monolayer culture of pancreatic B-cells / Streptozotocin / 3-O-methyl-streptozotocin / Experimental diabetes / Cellular immunity / エチリデングルコーズ |
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| Research Abstract |
1. A system of pancreatic B-cell culture was established. The pancreatic tissues from new-born rats were digested with 0.2% trypsin and 0.1% collagenase, and the dispersed cells were cultured in medium 199 including 16.7 mM glucose. The cultured cells maintained good morphological appearances and a high rate of insulin secretion under these conditions for over 10 days.
2. A new diabetogenic streptozotocin analogue, 3-O-methyl-streptozotocin, was synthesized. The critical point of this synthesis was nitrosylation of an immediadte precursor compound of the final product. This difficulty was overcomed by using 40% acetic acid solution of NaN <O_2> . These conditions enabled us to establish a stable synthetic procedure of this new biologically active compound.
3. In vivo effects of 3-O-methyl-streptozotocin and streptozotocin were compared in rats. A variety of parameters tested suggested that the cytotoxicity for pancreatic B-cells of 3-O-methyl-streptozotocin was milder than that of streptozotocin.
4. A consecutive administration of sub-dose of streptozotocin in rats induced delayed hyperglycemia and low glucose tolerance. We examined wether an immunologic mechanism was involved in this phenomenon. However, such possibility was excluded by using ethylidene glucose as a probe. Therefore, species difference was thought to be an important factor for the onset of immunologic diabetes in experimental animals.
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