To evaluate whether metformin enhances leptin sensitivity, we measured leptin sensitivity after 4 weeks of metformin treatment (300 mg/kg daily) in both standard chow and high-fat-fed obese rats. Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 g daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat-fed obese rats compared with age-matched standard chow rats. However, these responses to leptin were corrected by metformin treatment in high-fat-fed obese rats. Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats. The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. In an acute study, metformin treatment also increased the anorexic effect of leptin (5 g), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity. Diabetes 55:716 -724, 2006 L eptin, an adipocyte-derived hormone, contributes to body weight homeostasis by regulating food intake and energy expenditure (1). However, leptin is not widely used in the clinical field because obesity is accompanied by elevated serum leptin and responds poorly to the pharmacological administration of exogenous leptin, which ordinarily potently promotes fat mass loss and body weight reduction in lean subjects (2,3); moreover, this poor response of obese subjects is a characteristic of leptin resistance. Thus, the correction of leptin resistance in obese individuals would allow leptin to be used to treat obesity.Metformin, an oral biguanide insulin-sensitizing agent, inhibits hepatic glucose production, enhances the effects of insulin on glucose uptake in skeletal muscles and adipocytes, and decreases intestinal absorption of glucose (4 -7). It is also well known that metformin administration reduces body weight (8,9). Moreover, metformin decreases leptin concentration in morbidly obese subjects (9,10) and in normal-weight healthy men (11). Although leptin concentration is closely related to body fat mass, the leptin-reducing effect of metformin cannot be fully explained by body weight reduction because metformin reduces leptin level even without changing body weight in normal-weight healthy men (11). However, the mechanisms by which metformin reduces body weight and leptin concentration are poorly understood. In addition, it has been recently reported that metformin targets AMP-activated protein kinase (AMPK), which is also activated by leptin (12-14). The above findings imply that a more delicate interaction takes place between metformin and leptin. We h...

The purpose of the present study was to evaluate the efficacy and safety of bipolar transurethral prostatectomy (TURP) using the Gyrus™ PlasmaKinetic System compared with conventional monopolar TURP. This study included 102 patients with benign prostatic hyperplasia (BPH) who underwent TURP from January 2003 to March 2005. In all, 49 consecutive patients had bipolar and 53 had monopolar TURP. All patients were assessed by preoperative and postoperative International Prostate Symptom Score (IPSS), uroflowmetry, transrectal ultrasonography, operative time, weight of resected tissue, change in serum sodium and hemoglobin, duration of catheter use, length of hospital stay, and complication rates. Significant improvement was seen postoperatively in both groups, and no difference was observed in the resection time, weight of resected tissue, change in serum sodium and hemoglobin, improvement of IPSS and peak flow rate (Qmax), or complication rates over the 12-month follow-up in both groups. There was, however, a significant difference in duration of catheter use and hospital stay. Duration of catheter use (2.28 days vs. 3.12 days) and hospital stay (3.52 days vs. 4.27 days) were shorter in the bipolar group ( p = 0.012 vs. p = 0.034, respectively). Our results demonstrate that bipolar TURP using the Gyrus™ Plasma Kinetic System is as effective as conventional monopolar TURP with the additional advantage of reduced length of catheter use and hospital stay. Bipolar TURP is a promising new technique that may prove to be a good alternative to conventional TURP in the future.

Obesity is a well-known risk factor for erectile dysfunction, which is associated with reduced penile nitric oxide synthase (NOS) expression. Recently it was reported that metformin activates AMP-activated protein kinase (AMPK), which increases the expression of neuronal (n) NOS and endothelial (e) NOS. Thus, to evaluate whether metformin restores NOS expression in penile tissue, we measured penile expression of nNOS and eNOS after 4 weeks of metformin treatment (300 mg/kg/d) in 5-month-old highfat-fed obese (HFO) rats. HFO rats have increased fat accumulation in visceral areas and marked suppression of nNOS and eNOS expression in penile tissue. However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue. The levels of AMPK and phosphorylated AMPK were also decreased in HFO rats but were subsequently elevated by metformin treatment. These results suggest that expression of NOS was suppressed by the high-fat diet but restored by metformin treatment. The effect of metformin on the expression of NOS may be associated with its activation of AMPK.

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