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Effects of chemical sympathectomy by means of 6-hydroxydopamine on insulin secretion and islet morphology in alloxan-diabetic mice.

Kvist Reimer, Martina LU ; Sundler, Frank LU and Ahrén, Bo LU (2002) In Cell and Tissue Research1974-01-01+01:00 307(2). p.203-209
Abstract
Abstract. Activation of sympathetic nerves increases circulating glucose and inhibits insulin release from the islet beta-cells, which might contribute to stress-related diabetes. Accordingly, we have shown previously that blockade of parasympathetic activity aggravates diabetes in alloxan-treated mice, suggesting that unopposed sympathetic activity impairs diabetes. In this study, we tested whether elimination of sympathetic nerve activity by chemical sympathectomy with 6-hydroxydopamine (6-OHDA; 60 mg/kg) ameliorates the diabetogenic effects of alloxan (50 mg/kg) in NMRI mice. Mice given alloxan alone developed manifest diabetes after 2 days, as indicated by hyperglycemia. The diabetes persisted throughout the 35-day study period.... (More)
Abstract. Activation of sympathetic nerves increases circulating glucose and inhibits insulin release from the islet beta-cells, which might contribute to stress-related diabetes. Accordingly, we have shown previously that blockade of parasympathetic activity aggravates diabetes in alloxan-treated mice, suggesting that unopposed sympathetic activity impairs diabetes. In this study, we tested whether elimination of sympathetic nerve activity by chemical sympathectomy with 6-hydroxydopamine (6-OHDA; 60 mg/kg) ameliorates the diabetogenic effects of alloxan (50 mg/kg) in NMRI mice. Mice given alloxan alone developed manifest diabetes after 2 days, as indicated by hyperglycemia. The diabetes persisted throughout the 35-day study period. Pretreatment with 6-OHDA did not, however, affect the glucose levels or the low, 2-min in vivo insulin response to glucose (1 g/kg) after alloxan. In situ hybridization at day 35 revealed a significantly reduced grain area of insulin-mRNA in the alloxan-treated animals, which was not affected by 6-OHDA, and an altered islet architecture, with accumulation of glucagon cells in the central portion. Also 6-OHDA alone reduced the insulin mRNA area, but this was accompanied by an increase in the total islet area. We conclude that, in contrast to cholinergic inhibition, sympathectomy does not perturb the development of chemically induced diabetes in mice. Alone, however, sympathectomy reduces insulin gene expression and induces increased islet size, suggesting that sympathetic nerves are of importance for long-term islet function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Sympathectomy, Mouse (NMRI), 6-Hydroxydopamine, Sympathetic nerves, Glucagon, Diabetes, Alloxan, Insulin
in
Cell and Tissue Research1974-01-01+01:00
volume
307
issue
2
pages
203 - 209
publisher
Springer
external identifiers
  • pmid:11845327
  • wos:000174368200008
  • scopus:0036181571
ISSN
1432-0878
DOI
10.1007/s00441-001-0496-5
language
English
LU publication?
yes
id
3090e02c-7120-47f6-99c6-ace8349dd23d (old id 106037)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11845327&dopt=Abstract
date added to LUP
2007-07-16 13:40:33
date last changed
2017-08-06 03:30:07
@article{3090e02c-7120-47f6-99c6-ace8349dd23d,
  abstract     = {Abstract. Activation of sympathetic nerves increases circulating glucose and inhibits insulin release from the islet beta-cells, which might contribute to stress-related diabetes. Accordingly, we have shown previously that blockade of parasympathetic activity aggravates diabetes in alloxan-treated mice, suggesting that unopposed sympathetic activity impairs diabetes. In this study, we tested whether elimination of sympathetic nerve activity by chemical sympathectomy with 6-hydroxydopamine (6-OHDA; 60 mg/kg) ameliorates the diabetogenic effects of alloxan (50 mg/kg) in NMRI mice. Mice given alloxan alone developed manifest diabetes after 2 days, as indicated by hyperglycemia. The diabetes persisted throughout the 35-day study period. Pretreatment with 6-OHDA did not, however, affect the glucose levels or the low, 2-min in vivo insulin response to glucose (1 g/kg) after alloxan. In situ hybridization at day 35 revealed a significantly reduced grain area of insulin-mRNA in the alloxan-treated animals, which was not affected by 6-OHDA, and an altered islet architecture, with accumulation of glucagon cells in the central portion. Also 6-OHDA alone reduced the insulin mRNA area, but this was accompanied by an increase in the total islet area. We conclude that, in contrast to cholinergic inhibition, sympathectomy does not perturb the development of chemically induced diabetes in mice. Alone, however, sympathectomy reduces insulin gene expression and induces increased islet size, suggesting that sympathetic nerves are of importance for long-term islet function.},
  author       = {Kvist Reimer, Martina and Sundler, Frank and Ahrén, Bo},
  issn         = {1432-0878},
  keyword      = {Sympathectomy,Mouse (NMRI),6-Hydroxydopamine,Sympathetic nerves,Glucagon,Diabetes,Alloxan,Insulin},
  language     = {eng},
  number       = {2},
  pages        = {203--209},
  publisher    = {Springer},
  series       = {Cell and Tissue Research1974-01-01+01:00},
  title        = {Effects of chemical sympathectomy by means of 6-hydroxydopamine on insulin secretion and islet morphology in alloxan-diabetic mice.},
  url          = {http://dx.doi.org/10.1007/s00441-001-0496-5},
  volume       = {307},
  year         = {2002},
}