Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ). Also, in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE, and RQ when microinjected directly into the paraventricular nucleus (PVN). The anabolic peptide ghrelin served as a positive control in acute testing. 3V administration of both DET (0.5-2.0 mU) and regular insulin (2.0-8.0 mU) significantly reduced feeding and body weight over 48 and 120 h, respectively, with DET yielding greater inhibitory effects. DET also stimulated greater elevations of EE and reductions of RQ over 72 and 48 h postinjection, respectively. In acute (4 h) testing, microinjections of DET (0.5 mU) into the PVN reduced feeding, increased EE, and reduced RQ, while ghrelin (100 pmol) had the opposite effects. When administered sequentially into the PVN, DET (0.25 and 0.5 mU) reversed ghrelin-induced feeding, EE, and RQ effects. These data support the notion that the weight-sparing effect of DET is at least in part based on its central catabolic action and that enhanced EE and reduced RQ may participate in this effect.

No abstract

The present report examined the effects of midbrain raphe nuclei injections of nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) on eating behavior. L-NAME (5-500 pmol) and 7-NI (2-200 pmol) were administered into either the dorsal or median raphe nucleus. Both nitric oxide synthase inhibitors decreased food intake in adult male Sprague-Dawley rats when injected into either raphe site. Further, eating elicited by dorsal and median raphe injections of the 5-HT1A agonist 8-OH-DPAT (0.8 nmol) was attenuated by L-NAME or 7-NI pretreatment. Our findings indicate that nitric oxide acts within the raphe to alter food intake. The inhibitory effects of L-NAME and 7-NI on eating elicited by 8-OH-DPAT further suggest that nitric oxide and 5-HT systems interact in the control of food intake.

No abstract

No abstract