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Journal of Endocrinology (2008) 198, 541-548    DOI: 10.1677/JOE-08-0135
© 2008 Society for Endocrinology

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Guanethidine treatment does not block the ability of central leptin administration to decrease blood glucose concentrations in streptozotocin-induced diabetic rats

Jinpin Wang1, Catherine M Wernette1, Robert L Judd2, Kevin W Huggins1 and B Douglas White1

Departments of1 Nutrition and Food Science2 Anatomy, Physiology and Pharmacology, Auburn University, Auburn, Alabama 36849, USA

(Correspondence should be addressed to B D White; Email: whitebd{at}auburn.edu)

Leptin, administered either into the ventricles of the brain or systemically, has been shown to normalize blood glucose concentrations in streptozotocin (STZ)-induced diabetic rats. We hypothesized that an intact sympathetic nervous system is necessary for centrally administered leptin to normalize or attenuate high blood glucose concentrations in STZ-induced diabetic rats. Young male Wistar rats (~50 g) were treated every other day with either s.c. guanethidine (100 mg/kg) or vehicle for 2 weeks. Rats were then implanted with an intracerebroventricular cannula directed to the lateral ventricle and made diabetic with an i.v. injection of STZ (50 mg/kg). Half of the animals in each group were given daily injections of leptin (10 µl), while the remaining animals received vehicle injections. Blood glucose concentrations were measured daily and tissue norepinephrine content was determined by high performance liquid chromatography at the end of the study. Guanethidine pretreatment did not block the ability of centrally administered leptin to decrease blood glucose concentrations in diabetic rats. This suggests that the sympathetic nervous system does not mediate the leptin-induced attenuation of high blood glucose concentrations observed in diabetic rats.







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