RGD Reference Report - A Functional Melanocortin System May Be Required For Chronic Cns-Mediated Antidiabetic And Cardiovascular Actions Of Leptin. - Rat Genome Database

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A Functional Melanocortin System May Be Required For Chronic Cns-Mediated Antidiabetic And Cardiovascular Actions Of Leptin.

Authors: Da Silva, AA  Do Carmo, JM  Freeman, JN  Tallam, LS  Hall, JE 
Citation: da Silva AA, etal., Diabetes. 2009 Jun 2.
RGD ID: 2311124
Pubmed: PMID:19491210   (View Abstract at PubMed)
PMCID: PMC2712780   (View Article at PubMed Central)
DOI: DOI:10.2337/db08-1221   (Journal Full-text)

Objective: We recently showed that leptin has powerful 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 ICV infusions, and arterial and venous catheters were implanted to measure arterial pressure (MAP) and heart rate (HR) 24-h/d and for IV 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/hr), was infused ICV for 17 days. Seven days after starting the antagonist, leptin (0.62 mug/hr) was added to the ICV infusion for 10 days. Another group of diabetic rats was infused with the MC3/4R agonist, MTII (10 ng/hr, ICV), for 12 days, followed by 7 days at 50 ng/hr. Results: Induction of diabetes caused hyperphagia, hyperglycemia, and decreases in HR (-76 bpm) and MAP (-7 mmHg). Leptin restored appetite, blood glucose (BG), HR 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 BG and raised HR 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 which may involve interactions of multiple pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOLep (Rattus norvegicus)2311124; 2311124 RGD 
Experimental Diabetes Mellitus  IMP 2311124 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lep  (leptin)

Genes (Mus musculus)
Lep  (leptin)

Genes (Homo sapiens)
LEP  (leptin)


Additional Information