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Serum biopterin - a novel maker for immune activation during pre-diabetes in the BB rat

Serum biopterin - a novel maker for immune activation during pre-diabetes in the BB rat
Serum biopterin - a novel maker for immune activation during pre-diabetes in the BB rat
Tetrahydrobiopterin (BH4) is a pteridine product which is released by rodent macrophages on activation by cytokines. We have used serial pancreatic biopsy, and measurement of serum biopterin at 30,60,90 and 120 days in the BB/S rat to relate histological change to macrophage activation during the course of pre-diabetes. Using immunohistochemistry, and an arbitrary scoring system read blind and standardised against day 30, we found that pancreatic MHC class I, MHC class II and infiltrating macrophage staining were up-regulated in the BB/S diabetes-prone rats (n = 17) at day 60, markedly so at day 90, and less so at day 120. Staining for resident pancreatic macrophages remained unchanged throughout in diabetes prone, diabetes resistant and Wistar (n = 28) control animals. Serum biopterin fell progressively and identically with age in BB diabetes resistant rats (n = 11) and Wistar controls. No change in weight gain or biopterin levels was observed in the biopsied animals. Mean serum biopterin levels in diabetes prone rats (of which 13 of 17 became diabetic at median 85 days) were the same as in diabetes resistant and Wistar rats at days 30,60 and 120, but showed a striking and highly significant elevation (p > 0.001) at day 90. Although macrophages infiltrate the islet early in pre-diabetes, the timing of their activation is unknown. The rise in biopterin we observed is a potentially important immunological event which occurred late in the progression of pre-diabetes. This acute terminal event has not been reported previously, and may modify current concepts concerning the tempo of cell destruction during pre-diabetes.
0012-186X
466-470
Davies, A.J.
0fe6a40a-10d1-4ade-a7e6-d1dceb2470af
Bone, A.J.
40735ffe-53c9-46b4-a1ec-d516566e5d30
Wilkin, T.J.
56d0c5be-8c04-4ad3-bdf9-fef3c7fda856
Rokos, H.
26fec6d5-d478-4fed-a3f9-371d5f385159
Cole, D.R.
d025a53c-9f35-40f7-aded-78fa73c4fbeb
Davies, A.J.
0fe6a40a-10d1-4ade-a7e6-d1dceb2470af
Bone, A.J.
40735ffe-53c9-46b4-a1ec-d516566e5d30
Wilkin, T.J.
56d0c5be-8c04-4ad3-bdf9-fef3c7fda856
Rokos, H.
26fec6d5-d478-4fed-a3f9-371d5f385159
Cole, D.R.
d025a53c-9f35-40f7-aded-78fa73c4fbeb

Davies, A.J., Bone, A.J., Wilkin, T.J., Rokos, H. and Cole, D.R. (1994) Serum biopterin - a novel maker for immune activation during pre-diabetes in the BB rat. Diabetologia, 37 (5), 466-470. (doi:10.1007/s001250050133).

Record type: Article

Abstract

Tetrahydrobiopterin (BH4) is a pteridine product which is released by rodent macrophages on activation by cytokines. We have used serial pancreatic biopsy, and measurement of serum biopterin at 30,60,90 and 120 days in the BB/S rat to relate histological change to macrophage activation during the course of pre-diabetes. Using immunohistochemistry, and an arbitrary scoring system read blind and standardised against day 30, we found that pancreatic MHC class I, MHC class II and infiltrating macrophage staining were up-regulated in the BB/S diabetes-prone rats (n = 17) at day 60, markedly so at day 90, and less so at day 120. Staining for resident pancreatic macrophages remained unchanged throughout in diabetes prone, diabetes resistant and Wistar (n = 28) control animals. Serum biopterin fell progressively and identically with age in BB diabetes resistant rats (n = 11) and Wistar controls. No change in weight gain or biopterin levels was observed in the biopsied animals. Mean serum biopterin levels in diabetes prone rats (of which 13 of 17 became diabetic at median 85 days) were the same as in diabetes resistant and Wistar rats at days 30,60 and 120, but showed a striking and highly significant elevation (p > 0.001) at day 90. Although macrophages infiltrate the islet early in pre-diabetes, the timing of their activation is unknown. The rise in biopterin we observed is a potentially important immunological event which occurred late in the progression of pre-diabetes. This acute terminal event has not been reported previously, and may modify current concepts concerning the tempo of cell destruction during pre-diabetes.

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Published date: 1994

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Local EPrints ID: 73370
URI: https://eprints.soton.ac.uk/id/eprint/73370
ISSN: 0012-186X
PURE UUID: 7b66376e-ee24-43ce-8a34-baac85fe6925

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Date deposited: 09 Mar 2010
Last modified: 13 Jun 2018 16:32

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