Systemic treatment with sympatholytic dopamine agonists improves aberrant β-cell hyperplasia and GLUT2, glucokinase, and insulin immunoreactive levels in ob/ob mice

Sympatholytic dopamine agonist treatment utilizing bromocriptine and SKF38393 (BC/SKF) significantly lowers basal plasma insulin levels and normalizes basal and glucose-induced insulin secretion of the pancreatic beta cell in ob/ob mice. While BC/SKF has no significant effect on pancreatic islet cel...

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Bibliographic Details
Published in:Metabolism, clinical and experimental clinical and experimental, 2001-11, Vol.50 (11), p.1377-1384
Main Authors: JETTON, Thomas L, YIN LIANG, CINCOTTA, Anthony H
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Biological and medical sciences
Cell Division - drug effects
Diabetes. Impaired glucose tolerance
DNA - metabolism
Dopamine Agonists - pharmacology
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Glucagon - metabolism
Glucokinase - metabolism
Glucose Transporter Type 2
Hormones. Endocrine system
Hyperplasia - pathology
Hyperplasia - prevention & control
Immunohistochemistry
In Situ Nick-End Labeling
Insulin - metabolism
Islets of Langerhans - drug effects
Islets of Langerhans - metabolism
Islets of Langerhans - pathology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Obese
Monosaccharide Transport Proteins - metabolism
Pharmacology. Drug treatments
Somatostatin - metabolism
Sympatholytics - pharmacology
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Summary:Sympatholytic dopamine agonist treatment utilizing bromocriptine and SKF38393 (BC/SKF) significantly lowers basal plasma insulin levels and normalizes basal and glucose-induced insulin secretion of the pancreatic beta cell in ob/ob mice. While BC/SKF has no significant effect on pancreatic islet cells directly, drug action is mediated via alterations in the hypothalamic-neuroendocrine axis, which drives metabolic changes in peripheral tissues leading to a marked reduction in hyperglycemia and hyperlipidemia and corrects autonomic control of islet function. To elucidate the nature of the functional response of islets to systemic BC/SKF treatment in ob/ob mice, we investigated the relative changes in the levels of functionally important beta-cell proteins in situ, as well as differences in the beta-cell turnover rate, following a 2-week drug treatment. Isolated islets from treated mice exhibit a 3.5-fold increase in insulin content (P
ISSN:0026-0495
1532-8600
DOI:10.1053/meta.2001.26741