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Central NPY deficiency does not enhance the chronic actions of melanocortin 3 and 4 receptors (MC3/4R) activation on glucose homeostasis, appetite and cardiovascular function in diabetic mice
Author(s) -
Freeman John Nathan,
Carmo Jussara M.,
Hall John E.,
Silva Alexandre A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.597.6
Subject(s) - medicine , endocrinology , appetite , neuropeptide y receptor , melanocortin , streptozotocin , diabetes mellitus , glucose homeostasis , agonist , insulin , blood pressure , homeostasis , type 2 diabetes , receptor , chemistry , insulin resistance , neuropeptide
Acute studies suggest that NPY and MC3/4R exert opposite effects on appetite, cardiovascular and metabolic functions. This study tested if the responses to chronic MC3/4R activation on appetite, glucose levels (GLU), blood pressure (BP), and heart rate (HR) are altered in NPY deficient (NPY(−/−)) mice compared to wild‐type (WT) mice after induction of insulin‐deficient diabetes by streptozotocin (STZ) injection, an experimental model of diabetes associated with high central NPY levels. Despite lower baseline GLU compared to WT mice (139±6 vs 241±10 mg/dl), NPY(−/−) mice exhibited similar GLU 7 days after STZ injection (472±26 and 496±3 mg/dl). Food intake also increased similarly in both groups (3.7±0.2 to 7.0±1.0 and 3.6±0.3 to 6.0±1.4 g/day, respectively for NPY(−/−) and WT mice). No changes in HR or BP were observed 7 days after STZ injection (NPY(−/−) mice: 560±11 to 561±12 bpm and 113±2 to 116±4 mmHg; WT: 561±1 to 542±11 bpm and 103±3 to 108±2 mmHg). Infusion of the MC3/4R agonist MTII (120 μg/day, i.p. delivered by osmotic pumps) for 7 days did not significantly alter BP or HR in both groups, and did not attenuate the continuous rise in GLU (681±35 and 717±23 mg/dl) or food intake (9.8±1.4 and 9.2 0.3 g/day, respectively for NPY(−/−) and WT mice). Our results indicate that central deficiency of NPY does not exacerbate the chronic effects of MC3/4R activation to suppress appetite, to reduce GLU, or to increase BP and HR.