A functional melanocortin system may be required for chronic CNS-mediated antidiabetic and cardiovascular actions of leptin.

Abstract:

OBJECTIVE:We recently showed that leptin has powerful central nervous system (CNS)-mediated antidiabetic and cardiovascular actions. This study tested whether the CNS melanocortin system mediates these actions of leptin in diabetic rats. RESEARCH DESIGN AND METHODS:A cannula was placed in the lateral ventricle of Sprague-Dawley rats for intracerebroventricular infusions, and arterial and venous catheters were implanted to measure mean arterial pressure (MAP) and heart rate 24 h/day and for intravenous infusions. After recovery from surgery for 8 days, rats were injected with streptozotocin (STZ), and 5 days later, either saline or the melanocortin 3 and 4 receptor (MC3/4R) antagonist SHU-9119 (1 nmol/h) was infused intracerebroventricularly for 17 days. Seven days after starting the antagonist, leptin (0.62 microg/h) was added to the intracerebroventricular infusion for 10 days. Another group of diabetic rats was infused with the MC3/4R agonist MTII (10 ng/h i.c.v.) for 12 days, followed by 7 days at 50 ng/h. RESULTS:Induction of diabetes caused hyperphagia, hyperglycemia, and decreases in heart rate (-76 bpm) and MAP (-7 mmHg). Leptin restored appetite, blood glucose, heart rate, and MAP back to pre-diabetic values in vehicle-treated rats, whereas it had no effect in SHU-9119-treated rats. MTII infusions transiently reduced blood glucose and raised heart rate and MAP, which returned to diabetic values 5-7 days after starting the infusion. CONCLUSIONS:Although a functional melanocortin system is necessary for the CNS-mediated antidiabetic and cardiovascular actions of leptin, chronic MC3/4R activation is apparently not sufficient to mimic these actions of leptin that may involve interactions of multiple pathways.

journal_name

Diabetes

journal_title

Diabetes

authors

da Silva AA,do Carmo JM,Freeman JN,Tallam LS,Hall JE

doi

10.2337/db08-1221

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

1749-56

issue

8

eissn

0012-1797

issn

1939-327X

pii

db08-1221

journal_volume

58

pub_type

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