Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.

There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit Ϸ40% homology with ␣1-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulinsensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat highsucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNF␣, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in Ϸ50% of the high-fat high-sucroseinduced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.metabolic syndrome ͉ diabetes ͉ insulin resistance ͉ mesenteric ͉ white adipose tissue

STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.

We present the design and performance of the High Dispersion Spectrograph (HDS) of the Subaru Telescope. HDS is an echelle spectrograph located at the Nasmyth focus of the telescope. The collimated beam size is 272 mm, and the echelle is 300 mm by 840 mm in total size ($31.6 \,\mathrm{gr} \,\mathrm{mm}^{-1}, R=2.8$). HDS has two cross-dispersing gratings with $400 \,\mathrm{gr} \,\mathrm{mm}^{-1}$ and $250 \,\mathrm{gr} \,\mathrm{mm}^{-1}$, which are optimized for the blue and red wavelength regions, respectively. The camera is of the catadioptric type system, consisting of three corrector lenses and a mirror. Two EEV-CCD’s with $4100 \times 2048$ pixels and a pixel size of 13.5 ${\mu \mathrm {m}}$ are used as the detector. A standard configuration with a ${0\rlap {.}{}^{\mathrm {\prime \prime }}4}$ slit gives a spectral resolution of $R=90000$, and a narrower slit width enables higher resolution of up to $R \sim 160000$. The spectrograph has sensitivities from 3000 ${Å}$ to 1 ${\mu \mathrm {m}}$, and one exposure covers a range of 1500–2500 ${Å}$, depending on the wavelength region. The throughput of the telescope and the spectrograph, including the efficiency of the detector, is about 13% in 5000–6000 ${Å}$ and about 8% at 4000 ${Å}$. The stability of the spectrograph and scattered light level are also reported.

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ABSTRACTwhich falls in the planetary-mass regime. This is the first discovery of a planetary companion orbiting a G-type giant star.

OBJECTIVEAn increase in the rate of gluconeogenesis is largely responsible for the hyperglycemia in individuals with type 2 diabetes, with the antidiabetes action of metformin being thought to be achieved at least in part through suppression of gluconeogenesis.RESEARCH DESIGN AND METHODSWe investigated whether the transcription factor KLF15 has a role in the regulation of gluconeogenesis and whether KLF15 participates in the antidiabetes effect of metformin.RESULTSHere we show that KLF15 regulates the expression of genes for gluconeogenic or amino acid–degrading enzymes in coordination with the transcriptional coactivator peroxisome proliferator–activated receptor γ coactivator 1α. Liver-specific ablation of KLF15 in diabetic mice resulted in downregulation of the expression of genes for gluconeogenic or amino acid catabolic enzymes and in amelioration of hyperglycemia. Exposure of cultured hepatocytes to metformin reduced the abundance of KLF15 through acceleration of its degradation and downregulation of its mRNA. Metformin suppressed the expression of genes for gluconeogenic or amino acid–degrading enzymes in cultured hepatocytes, and these effects of metformin were attenuated by restoration of KLF15 expression. Administration of metformin to mice inhibited both the expression of KLF15 and glucose production in the liver, the latter effect also being attenuated by restoration of hepatic KLF15 expression.CONCLUSIONSKLF15 plays an important role in regulation of the expression of genes for gluconeogenic and amino acid–degrading enzymes and that the inhibitory effect of metformin on gluconeogenesis is mediated at least in part by downregulation of KLF15 and consequent attenuation of the expression of such genes.