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

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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; Sundler, Frank; Ahrén, Bo.

In: Cell and Tissue Research, Vol. 307, No. 2, 2002, p. 203-209.

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T1 - Effects of chemical sympathectomy by means of 6-hydroxydopamine on insulin secretion and islet morphology in alloxan-diabetic mice.

AU - Kvist Reimer, Martina

AU - Sundler, Frank

AU - Ahrén, Bo

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medicine (Lund) (013230025), Neuroendocrine Cell Biology (013212008)

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Sympathectomy

KW - Mouse (NMRI)

KW - 6-Hydroxydopamine

KW - Sympathetic nerves

KW - Glucagon

KW - Diabetes

KW - Alloxan

KW - Insulin

U2 - 10.1007/s00441-001-0496-5

DO - 10.1007/s00441-001-0496-5

M3 - Article

VL - 307

SP - 203

EP - 209

JO - Cell and Tissue Research

JF - Cell and Tissue Research

SN - 1432-0878

IS - 2

ER -