Ghrelin is produced mainly by endocrine cells in the stomach and is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). It also influences feeding behavior, metabolic regulation, and energy balance. It affects islet hormone secretion, and expression of ghrelin and GHS-R in the pancreas has been reported. In human islets, ghrelin expression is highest pre- and neonatally. We examined ghrelin and GHS-R in rat islets during development with immunocytochemistry and in situ hybridization. We also studied the effect of ghrelin on insulin secretion from INS-1 (832/13) cells and the expression of GHS-R in these cells. We found ghrelin expression in rat islet endocrine cells from mid-gestation to 1 month postnatally. Islet expression of GHS-R mRNA was detected from late fetal stages to adult. The onset of islet ghrelin expression preceded that of gastric ghrelin. Islet ghrelin cells constitute a separate and novel islet cell population throughout development. However, during a short perinatal period a minor subpopulation of the ghrelin cells co-expressed glucagon or pancreatic polypeptide. Markers for cell lineage, proliferation, and duct cells revealed that the ghrelin cells proliferate, originate from duct cells, and share lineage with glucagon cells. Ghrelin dose-dependently inhibited glucose-stimulated insulin secretion from INS-1 (832/13) cells, and GHS-R was detected in the cells. We conclude that ghrelin is expressed in a novel developmentally regulated endocrine islet cell type in the rat pancreas and that ghrelin inhibits glucose-stimulated insulin secretion via a direct effect on the beta-cell.

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Lipids may serve as coupling factors in K ATP -independent glucose sensing in ␤-cells. We have previously demonstrated that ␤-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether ␤-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in K ATP -independent glucose sensing has been perturbed. Thus, ␤-cell lipase activity is involved in GSIS, emphasizing the important role of ␤-cell lipid metabolism for insulin secretion. Diabetes 53:122-128, 2004A large body of evidence suggests that lipids are required for appropriate glucose sensing in pancreatic ␤-cells. For instance, when triglycerides in pancreatic islets are depleted by hyperleptinemia, pancreatic ␤-cells fail to release insulin (1). Along similar lines, perfused pancreas from fasted rats is unresponsive to a rise in glucose (2). Importantly, in both cases, glucose responsiveness is reinstated by the addition of exogenous fatty acids.The current view holds that lipids serve as coupling factors in glucose-stimulated insulin secretion (GSIS) that does not rely on closure of the ATP-sensitive K ϩ channel (K ATP independent) (3). These putative mechanisms presumably drive the second phase of GSIS and accordingly have been termed as amplifying (4), and the coupling factors have been proposed to emanate from intermediary metabolism in the ␤-cell (5). Against this background, lipids have become attractive candidates for coupling factors in K ATP -independent glucose sensing. In fact, a model has been proposed to delineate the combined events in metabolism of glucose and lipids that result in a dose-dependent regulation of insulin secretion, the socalled long-chain acyl-CoA hypothesis (3). This model is based on the observations that an increase in glucose metabolism in ␤-cells results in decreased oxidation of fats while esterification of lipids increases. As a consequence, the levels of complex lipids rise, perhaps acyl-CoA moieties, which then act as a signaling molecules coupling stimulus to secretion in the ␤-cell. We have previously demonstrated that different preparations of ␤-cells...

We use the dynamical cluster approximation to understand the proximity of the superconducting dome to the quantum critical point in the two-dimensional Hubbard model. In a BCS formalism, T may be c enhanced through an increase in the d-wave pairing interaction (V d ) or the bare pairing susceptibility (x 0d ). At optimal doping, where V d is revealed to be featureless, we find a power-law behavior of x 0d ð! ¼ 0Þ, replacing the BCS log, and strongly enhanced T c . We suggest experiments to verify our predictions. DOI: 10.1103/PhysRevLett.106.047004 PACS numbers: 74.20.Fg, 71.10.-w, 74.25.Dw Introduction.-The unusually high superconducting transition temperature of the cuprates remains an unsolved puzzle, despite more than two decades of intense theoreti cal and experimental research. Central to the efforts to unravel this mystery is the idea that the high critical temperature is due to the presence of a quantum critical point (QCP) which is hidden under the superconducting dome [1]. Numerical calculations in the Hubbard model, which is accepted as the defacto model for the cuprates, strongly support the case of a finite-doping QCP separating the low-doping region, found to be a non-Fermi liquid (NFL), from a higher doping Fermi-liquid (FL) region [2,3]. Calculations also show that in the vicinity of the QCP, and for a wide range of temperatures, the doping and temperature dependence of the single-particle properties, such as the quasiparticle weight [2], as well as thermody namic properties such as the chemical potential and the entropy, are consistent with marginal Fermi liquid (MFL) behavior [4]. This QCP emerges by tuning the temperature of a second-order critical point of charge separation transitions to zero and is therefore intimately connected to q ¼ 0 charge fluctuations [5]. Finally, the critical doping seems to be in close proximity to the optimal doping for superconductivity as found both in the context of the Hubbard [5] and the t-J model [6]. Even though this proximity may serve as an indication that the QCP enhan ces pairing, the detailed mechanism is largely unknown.In this Letter, we attempt to differentiate between two incompatible scenarios for the role of the QCP in super conductivity. The first scenario is the quantum critical BCS (QCBCS) formalism introduced by She and Zaanen (SheZaanen) [7]. According to this, the presence of the QCP results in replacing the logarithmic divergence of the BCS pairing bubble by an algebraic divergence. This leads to a stronger pairing instability and higher critical temperature

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A feeding trial was conducted to investigate the in£uence of dietary protein levels on growth performance, carcass proximate composition and liver lipid classes of juvenile Spinibarbus hollandi (Oshima), a cyprinid ¢sh.White ¢sh meal was the primary protein source in the study. Eight experimental diets containing 13^55% crude protein were fed to three replicate groups of six ¢sh weighing nearly 8.5 g each for 10 weeks. Both percentage weight gain and feed e⁄ciency ratio increased signi¢cantly with increasing dietary protein levels up to 31%, but there was no further increase for protein levels from 31% to 55%. Application of broken-line regression analysis to the percentage weight gain provided an estimate of 32.771.5% dietary protein for maximum growth. The protein e⁄ciency ratio and productive lipid value were inversely correlated with dietary protein level. The hepatosomatic index and the viscerosomatic index were also inversely related to dietary protein level. The carcass protein of ¢sh fed lower protein diets was signi¢cantly lower than that of the ¢sh fed higher protein diets. Carcass lipid content decreased with increasing dietary protein levels, whereas moisture was inversely related to lipid content. Both liver glycogen and liver lipid contents decreased with increasing dietary protein levels. Triglyceride was the major component in the liver lipid, and the amount of triglyceride deposited in the liver also decreased with dietary protein levels. The results indicated that both carcass proximate composition and liver lipid class of juvenile Spinibarbus hollandi were a¡ected by dietary treatments.

We find that imposing the crossing symmetry in the iteration process considerably extends the range of convergence for solutions of the parquet equations for the Hubbard model. When the crossing symmetry is not imposed, the convergence of both simple iteration and more complicated continuous loading (homotopy) methods are limited to high temperatures and weak interactions. We modify the algorithm to impose the crossing symmetry without increasing the computational complexity. We also imposed time reversal and a subset of the point group symmetries, but they did not further improve the convergence. We elaborate the details of the latency hiding scheme which can significantly improve the performance in the computational implementation. With these modifications, stable solutions for the parquet equations can be obtained by iteration more quickly even for values of the interaction that are a significant fraction of the bandwidth and for temperatures that are much smaller than the bandwidth. This may represent a crucial step towards the solution of two-particle field theories for correlated electron models.