The present study aimed to examine whether
hyperphagia, which is frequently observed in type 1 diabetic patients and model animals, also occurs in type 2 diabetic Goto-Kakizaki (GK) rats and, if so, to explore underlying abnormalities in the hypothalamus. GK rats at postnatal weeks 6-12, compared to control Wistar rats, exhibited
hyperphagia, hyperglycaemia, hyperleptinemia and increased visceral fat accumulation, whereas
body weight was unaltered. The ability of
leptin to suppress feeding was reduced in GK rats compared to Wistar rats of these ages. In GK rats,
leptin-induced phosphorylation of
signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus (
ARC), but not of the ventromedial hypothalamus, whereas the
mRNA level of functional
leptin receptor was unaltered. By real-time polymerase chain reaction and in situ hybridisation,
mRNA levels of
neuropeptide Y, but not
pro-opiomelanocortin and
galanin-like peptide, were significantly increased in the
ARC of GK rats at 11 weeks, but not 26 weeks. Following i.c.v. injection of a NPY Y1 antagonist,
1229U91, the amount of food intake in GK rats was indistinguishable from that in Wistar rats, thus eliminating the
hyperphagia of GK rats. These results demonstrate that young adult GK rats display
hyperphagia in association with
leptin resistance and increased NPY
mRNA level in the
ARC.