Effects of chemical sympathectomy by means of 6-hydroxydopamine on insulin secretion and islet morphology in alloxan-diabetic mice.
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.
Kvist-Reimer
Martina
M
Department of Medicine, Lund University, B11 BMC, 221 84 Lund, Sweden.
Sundler
Frank
F
Ahrén
Bo
B
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D016627:Oxidopamine; D012333:RNA, Messenger / Q000032:analysis; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013565:Sympatholytics; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013565:Sympatholytics; D016627:Oxidopamine