Compared with controls, HZ cases had lower VZV-specific CD8(+) CD107a(+) cell percentages independently of CD4(+) percentages or HIV loads, suggesting that VZV-specific cytotoxic T cells are protective against HZ. In contrast, high nonspecific regulatory and activated T cells were associated with an increased risk of

HZ.”
“Adenosine receptors co-localize with dopamine www.selleckchem.com/products/AZD6244.html receptors on medium spiny nucleus accumbens (NAc) neurons where they antagonize dopamine receptor activity. It remains unclear whether adenosine receptor stimulation in the NAc restores cocaine-induced enhancements in dopamine receptor sensitivity. The goal of these studies was to determine whether stimulating A(1) or A(2A) receptors in the NAc reduces the expression of cocaine sensitization. Rats were sensitized with 7 daily treatments of cocaine (15 mg/kg, i.p.). Following one-week withdrawal, the effects

of intra-NAc microinjections of the adenosine kinase inhibitor (ABT-702), the adenosine deaminase inhibitor (deoxycoformycin: DCF), the specific A(1) receptor agonist (CPA) and the specific A(2A) receptor agonist (CGS 21680) were tested on the behavioral expression of cocaine sensitization. The results indicate that intra-NAc Apoptosis inhibitor pretreatment of ABT-702 and DCF dose-dependently blocked the expression of cocaine sensitization while having no effects on acute cocaine sensitivity, suggesting that upregulation of endogenous adenosine in the accumbens is sufficient to non-selectively stimulate adenosine receptors and reverse the expression of cocaine sensitization. Intra-NAc treatment of CPA significantly inhibited the expression of cocaine sensitization, which was reversed by both

A(1) and A(2A) receptor antagonism. Intra-NAc treatment of CGS 21680 also significantly inhibited the expression of cocaine sensitization, which was selectively reversed by A(2A), but not A(1), receptor antagonism. Finally. CGS 21680 also inhibited the expression Dynein of quinpirole cross-sensitization. Together, these findings suggest that adenosine receptor stimulation in the NAc is sufficient to reverse the behavioral expression of cocaine sensitization and that A(2A) receptors blunt cocaine-induced sensitization of postsynaptic D-2 receptors. (C) 2012 Elsevier Ltd. All rights reserved.”
“Aim: To investigate the effect of antivenom and fresh frozen plasma (FFP) on recovery of VICC in Australian elapid snake envenoming.

Design: Prospective cohort study.

Methods: Patients with VICC were included from the Australian Snakebite Project (ASP). Time to recovery of VICC (defined as time until INR < 2) was investigated using a time to event analysis in WinBUGS. The model considered the effects of age, sex, snake type, time of antivenom after bite, antivenom dose and use of FFP within 4 h.

We also found that the core lysine mutants display wild-type sensitivity to the antiviral activity of interferon, which Immunology inhibitor demonstrates that ubiquitination of core lysines does not mediate the interferon-induced disruption of HBV capsids. However, mutation of K96 to arginine alters the nuclear-cytoplasmic

distribution of core, leading to an accumulation in the nucleolus. In summary, these studies demonstrate that although ubiquitin may regulate the HBV replication cycle, these mechanisms function independently of direct lysine ubiquitination of core protein.”
“Previous studies have suggested a role for both CB1 and CB2 cannabinoid receptors in modulation of nociception. To further examine the role of

CBI and CB2 receptors in antinociception, we evaluated the efficacy of the non-selective cannabinoid receptor agonist, CP 55,940, in models of acute, inflammatory, and neuropathic pain in control mice, CB1 receptor knockout mice, and CB2 receptor knockout mice. In control C57BL/6 mice, administration of CP 55,940 (0.03-0.3 mg/kg, i.p.) reversed complete Freund’s adjuvant-induced tactile allodynia, reversed tactile allodynia in the spinal nerve ligation model and inhibited the noxious heat-evoked tail withdrawal response. In addition to its antinociceptive effects, CP 55,940 produced an impairment of motor coordination in the rotarod selleck inhibitor test. The antinociceptive effects produced by CP 55,940 and associated motor deficits were found to be completely abolished in CB1 receptor knockout mice. In contrast, the antinociceptive effects of CP MycoClean Mycoplasma Removal Kit 55,940 in all pain models were fully retained in CB2 receptor knockout mice, along with the associated motor deficits. The results suggest that the antinociceptive effects of CP 55,940 in models of acute and persistent pain, along with the associated motor deficits, are mediated by CB1 receptors, and likely not CB2 receptors. (C) 2009 Published by Elsevier Ltd.”
“CD4 T cells have been shown to play an important role in the immunity and immunopathogenesis

of respiratory syncytial virus (RSV) infection. We identified two novel CD4 T-cell epitopes in the RSV M and M2 proteins with core sequences M(213-223) (FKYIKPQSQFI) and M2(27-37) (YFEWPPHALLV). Peptides containing the epitopes stimulated RSV-specific CD4 T cells to produce gamma interferon (IFN-gamma), interleukin 2 (IL-2), and other Th1- and Th2-type cytokines in an I-A(b)-restricted pattern. Construction of fluorochrome-conjugated peptide-I-A(b) class II tetramers revealed RSV M- and M2-specific CD4 T-cell responses in RSV-infected mice in a hierarchical pattern. Peptide-activated CD4 T cells from lungs were more activated and differentiated, and had greater IFN-gamma expression, than CD4 T cells from the spleen, which, in contrast, produced greater levels of IL-2.

The final yield of purified rhATX S48 was approximately 3.5 mg/l culture of recombinant strain. The rhATX S48 shows lysoPLD enzymatic SC75741 activity and effectively stimulates the growth and motile activity of the human tumor cells as well as native ATX.

This is a first report for scalable purification of the ATX molecule and the rhATX S48 should be a good tool for immunization of anti-ATX

or crystallographic analysis of ATX (C) 2007 Elsevier Inc. All rights reserved.”
“A single nanopore represents an amazingly versatile single-molecule probe that can be employed to reveal several important features of polypeptides, such as their folding state, backbone flexibility, mechanical stability, binding affinity to other interacting ligands and enzymatic activity. Moreover, groundwork in this area using engineered protein nanopores has demonstrated new opportunities for discovering the biophysical rules that govern the transport of proteins through transmembrane

protein pores. In this review, I summarize the current knowledge in the field and discuss how nanopore probe techniques will provide a new generation of research tools in nanomedicine for quantitatively examining the details of complex recognition and, furthermore, will represent a crucial step in designing other pore-based nanostructures and high-throughput Defactinib purchase devices for molecular biomedical diagnosis.”
“Sleep disturbance is common in dialysis patients and is associated with the development of enhanced inflammatory responses. Cognitive-behavioral therapy is effective for sleep disturbance and reduces inflammation experienced by peritoneal dialysis patients; however, this has not been studied in hemodialysis patients. To determine whether alleviation of sleep disturbance in hemodialysis patients

also leads to less inflammation, we conducted a randomized controlled interventional study of 72 sleep-disturbed hemodialysis patients. Within this patient cohort, 37 received tri-weekly cognitive-behavioral therapy lasting 6 weeks and the remaining 35, who received sleep hygiene education, served as controls. The adjusted post-trial primary outcome scores of the Pittsburgh Sleep Quality Index, the Fatigue Severity Scale, the Beck Depression Aspartate Inventory, and the Beck Anxiety Inventory were all significantly improved from baseline by therapy compared with the control group. The post-trial secondary outcomes of high-sensitive C-reactive protein, IL-18, and oxidized low-density lipoprotein levels significantly declined with cognitive-behavioral therapy in comparison with the control group. Thus, our results suggest that cognitive-behavioral therapy is effective for correcting disorganized sleep patterns, and for reducing inflammation and oxidative stress in hemodialysis patients. Kidney International (2011) 80, 415-422; doi: 10.1038/ki.2011.

However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation.

Materials and Methods: We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable

Cox regression VE-821 research buy models addressed progression-free survival and cancer specific survival.

Results: Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 +/- 37.8 and 54.4 +/- 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial

nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) this website and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates.

Conclusions: To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.”
“Purpose: Renal cell carcinoma is sometimes associated with bone metastasis. Several risk factors have been reported but some Erythromycin are still controversial. Also, the significance of laboratory tests has not been fully examined for such cases.

Materials and Methods: We collected data on 94 renal cell carcinoma cases with bone metastasis treated at 3 tertiary referral centers.

Clinicopathological parameters and outcome data were analyzed to search for predictors of overall survival retrospectively. The log rank test and the Cox proportional hazard model were used for univariate and multivariate analyses, respectively.

Results: There were 64 males with a median age of 63.9 years. Histological diagnosis showed clear cell renal cell carcinoma in 63 patients, nonclear cell renal cell carcinoma in 7 and unclassified cancer in 6. Sarcomatoid differentiation was found in 17 cases. Metastasis was detected synchronously in 37 patients or metachronously at a median interval of 33.1 months. Multivariate analysis identified sarcomatoid differentiation (p = 0.001), vertebral bone involvement (p = 0.003), extraosseous metastasis (p = 0.021), alkaline phosphatase increased to 1.5 times the upper limit of normal (p = 0.

Once a pathogen is established, ecological factors related to vector characteristics can shape the evolutionary selective

pressure and result in increased use of people as transmission hosts. We describe challenges inherent in the control of vector-borne zoonotic diseases and some emerging non-traditional strategies that could be effective in the long term.”
“Age-related decline has been reported in most cognitive domains, including executive function: in particular, attentional set-shifting and reversal learning, as measures of executive control, are impaired in aged populations of both humans and rats. Despite the importance of the cholinergic system in age-related cognitive decline, no data GSK2879552 datasheet are available on the effects of cholinergic enhancement on age-related performance deficits in tests of attentional set-shifting.

We investigated the effects of the cholinesterase inhibitor tetrahydroacridin-9-amine (tacrine) on reversal learning and attentional set-shifting in older rats (aged 16-21 months) using the rodent version of the intradimensional/extradimensional attentional set-shifting task in a repeated-measures design. Discrimination acquisition was not impaired, but age-related impairments in reversal https://www.selleckchem.com/products/z-vad-fmk.html learning were persistent between tests, and ameliorated by the 3 mg/kg dose of tacrine. No age-related impairments in set-shifting were seen, but there was a tendency for tacrine to reduce the cost of shifting set. Given the lack of previous evidence for a role of cortical acetylcholine in attentional set-shifting tasks, it is likely that altered neurotransmitter interactions in striatum underlie this improvement. (C) 2013 Elsevier Ltd. All rights reserved.”
“Most pandemics-eg,

HIV/AIDS, severe acute respiratory syndrome, pandemic influenza-originate in animals, are Erlotinib supplier caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their substantial effects on global public health and growing understanding of the process by which they emerge, no pandemic has been predicted before infecting human beings. We review what is known about the pathogens that emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their control and new efforts to predict pandemics, target surveillance to the most crucial interfaces, and identify prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from response to pre-emption.

Of the 1648 cases for which clinical specimens were available, 50% were laboratory-confirmed. Orthodox Jewish persons accounted for 97% of case patients. Adolescents selleck chemical 13 to 17 years of age (27% of all patients) and males (78% of patients in that age group) were disproportionately affected. Among case patients 13 to 17 years of age with documented vaccination status, 89% had previously received two doses of a mumps-containing vaccine, and 8% had received one dose. Transmission

was focused within Jewish schools for boys, where students spend many hours daily in intense, face-to-face interaction. Orchitis was the most common complication (120 cases, 7% of male patients >= 12 years of age), with rates significantly higher among unvaccinated persons than among persons who had received two doses of vaccine.

Conclusions

The epidemiologic features of this outbreak suggest that intense exposures, particularly among boys in schools, facilitated transmission and overcame vaccine-induced protection in these patients.

High rates of two-dose coverage reduced the severity of the disease and the transmission to persons in settings of less intense exposure.”
“In many animal species including humans circulating androgen levels in mates Selleck 4SC-202 respond to social challenges. This response has been interpreted as an adaptive mechanism that helps the individuals to adjust their behavior to changes in social context. According to this hypothesis socially modulated androgen levels (e.g. increased levels in dominants and decreased levels in subordinates) selleck inhibitor would influence the subsequent expression of social behavior in a status-dependent fashion. This rationale is partially based on mate physiology and therefore has been rarely investigated in females. Here, we investigated if a hormonal response to a social challenge that produces changes in status is also present in human females.

We have collected saliva from and administered questionnaires to female soccer players of both teams playing the final match of the Portuguese Female soccer league. Samples were collected on a neutral day and on the day of the game both before and after the match. The change in testosterone levels (i.e. post-game – pre-game values = Delta(T)) was positive in the winners and negative in the losers and there was a significant difference in the testosterone change (i.e. Delta(T)) over the game between winners and losers. Cortisol levels did not vary with contest outcome. An anticipatory rise in circulating levels of both hormones (testosterone and cortisol) was detected before the match. Paralleling the hormonal responses, changes in mood and anxiety state were also found between both teams, with more positive states being observed in winners and more negative states being observed in losers at the end of the match.

Outcomes of interest were: MACE [the composite of all cause death, MI, repeat target vessel PCI (re-PCI) and coronary artery bypass grafting (CABG)]; single end points were also assessed.

Results: Fifteen studies have been included totalling 7578 patients. Troponin elevation occurred in 28.7% of the procedures.

The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalization, any level of raised troponin was associated with an increased risk of MACE [OR 11.29 (3.00-42.48), Number needed to harm (NNH) 5], death [OR 7.16 (1.95-26.27), NNH = 100], MI [OR 30.85 (6.05-157.38), NNH = 4] and re-PCI [OR 4.13 selleck (1.23-13.88), NNH = 50]. Patients with PCI-related MI had an increased risk of death [OR 17.25 (2.71-109.96), NNH = 100] and re-PCI [OR 10.86 (3.2-36.94), NNH = 25]. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE [OR 1.48 (1.12-1.96), NNH = 20], death [OR 2.19 (1.59-3.00), NNH = 50], MI [OR 3.29 (2.71-6.31), NNH = 33] and re-PCI [OR 1.47 (1.06-2.03), NNH = 25]. In patients

with PCI-related MI the risk of MACE was further increased: OR 2.25 (1.26-4.00), NNH = 3. An increase of the troponin level below the cut-off was not associated with MACE.

Conclusion: A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months.”
“Herpesviruses establish latency selleck chemical in suitable cells of the host organism after a

primary lytic infection. Subgroup C strains of herpesvirus saimiri (HVS), a primate gamma-2 herpesvirus, are able to transform human and other primate T lymphocytes to stable growth in vitro. The viral genomes persist Galeterone as nonintegrated, circular, and histone-associated episomes in the nuclei of those latently infected T cells. Epigenetic modifications of episomes are essential to restrict the transcription during latency to selected viral genes, such as the viral oncogenes stpC/tip and the orf73/LANA. In this study, we describe a genome-wide chromatin immunoprecipitation-on-chip (ChIP-on-chip) analysis to profile the occupancy of CTCF on the latent HVS genome. We then focused on two distinct, conserved CTCF binding sites (CBS) within the orf73/LANA promoter region. Analysis of recombinant viruses harboring deletions or mutations within the CBS indicated that the lytic replication of such viruses is not substantially influenced by CTCF. However, T cells latently infected with CBS mutants were impaired in their proliferation abilities and showed a significantly reduced episomal maintenance. We detected a reduced transcription of the orf73/LANA gene in the T cells, corresponding to the reduced viral genomes; this might contribute to the loss of HVS episomes, as LANA is central in the maintenance of viral episomes in the dividing T cell populations.

Further, atomoxetine treatment at CT6 induced a downregulation of c-Fos and CLOCK in the SCN, but did not alter the expression of PER2 and BMAL1. Atomoxetine during the night phase did not alter any of these factors. Atomoxetine treatment preceding a light pulse at CT15 enhanced the magnitude of the photic-phase shift, whereas it altered photic induction of the immediate early gene products c-Fos and ARC in the SCN. These data indicate that atomoxetine can reset the circadian clock and indicate that part of the therapeutic profile of atomoxetine may be through circadian rhythm modulation.

(C) 2011 IBRO. Published by Elsevier Ltd. All Evofosfamide datasheet rights reserved.”
“Intact intercellular junctions and cell-matrix contacts are important structures in the formation and maintenance of epithelial-barrier functions

against microbes. The human gastric pathogen Helicobacter pylori developed a remarkable network of strategies to alter these epithelial cell-cell and cell-matrix adhesions, which are implicated in inflammation, Defactinib proliferation, cell migration and invasive growth. This review focuses on recent findings on H. pylori-induced host-cell signaling. We propose a stepwise model for how H. pylori interacts with components of focal adhesions and intercellular tight and adherens junctions to disrupt the epithelial layer, providing novel insights into the pathogenesis of H. pylori.”
“Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular

cytotoxicity (ADCC) activity have been postulated to be important for control of HIV-1 infection. ADCC-mediating Ab must recognize HIV-1 antigens expressed on the membrane of infected cells and bind the Fc gamma receptor (FcR) of the effector cell population. However, the precise targets of serum ADCC antibody are poorly characterized. The human monoclonal antibody (MAb) A32 is a nonneutralizing antibody isolated from an HIV-1 chronically infected person. We investigated the ability of MAb A32 to recognize HIV-1 envelope expressed on the surface of CD4(+) T cells infected with primary and laboratory-adapted strains of HIV-1, as well as its ability to mediate ADCC activity. The MAb A32 epitope was expressed on the surface of HIV-1-infected CD4(+) T cells earlier than the CD4-inducible (CD4i) epitope bound by MAb 17b and VAV2 the gp120 carbohydrate epitope bound by MAb 2G12. Importantly, MAb A32 was a potent mediator of ADCC activity. Finally, an A32 Fab fragment blocked the majority of ADCC-mediating Ab activity in plasma of subjects chronically infected with HIV-1. These data demonstrate that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity.”
“Although the cancer stem cell (CSC) hypothesis has become an attractive model to account for tumor recurrence, failure to define a cell of origin has created the need to explore alternative models for cancer initiation and maintenance.

Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, Selleck Pifithrin�� and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes,

and haemoglobin A(1c). The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. PRT062607 mouse Treatment with candesartan did not reduce or prevent the development

of excessive excretion of urinary albumin.

Interpretation Increased UACR is a powerful and independent predictor of prognosis in heart failure.

Funding AstraZeneca.”
“BACKGROUND

The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.

METHODS

In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months

thereafter for 3 years.

RESULTS

In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; Imatinib research buy P = 0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P = 0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P = 0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed.

CONCLUSIONS

This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk.

Conclusions: In urban subjects without notable Eltanexor molecular weight chronic disease, the prevalence of CKD was 20.5%. Several metabolic abnormalities, i.e., dyslipidemia and hyperuricemia, were significantly associated with CKD. Copyright (c) 2012 S. Karger AG, Basel”
“Growing evidence suggests that ‘pro-inflammatory’cytokines such as TNF play a role in cognitive processes and in aging. To test the effects of TNF on cognitive function throughout aging, we used

transgenic mice which were TNF deficient. We then tested these mice along with wild-type mice, at 3, 6 and 12 months of age, using the Barnes maze. Wild-type controls showed better memory than TNF knock-out mice at 3 months of age, but not at 6 and 12 months of age. Results of our experiment show that endogenous TNF plays an important role in cognitive processes throughout aging processes. The implications of these findings are far-reaching and include a possible role for cytokines in check details the molecular and cellular mechanisms subserving age-related changes in learning, memory and cognition. (C) 2008 Elsevier Ltd. All rights reserved.”
“Known to be involved in emotional processing the human prefrontal cortex (PFC), can

be non-invasively monitored using near-infrared spectroscopy (NIRS). As such, PFC NIRS can serve as a means for studying emotional processing by the PFC. Identifying patterns associated with emotions in PFC using NIRS may provide a means of bedside emotion identification for nonverbal children and youth with severe physical disabilities. In this study, NIRS was used to characterize Elesclomol (STA-4783) the PFC

hemodynamic response to emotional arousal and valence in a music-based emotion induction paradigm in 9 individuals without disabilities or known health conditions. In particular, a novel technique based on wavelet-based peak detection was used to characterize chromophore concentration patterns. The maximum wavelet coefficients extracted from oxygenated hemoglobin concentration waveforms from all nine recording locations on the PFC were significantly associated with emotional valence and arousal. Specifically, high arousal and negative emotions were associated with larger maximum wavelet coefficients. (c) 2012 Published by Elsevier Ireland Ltd.”
“Glucose homeostasis requires the highly coordinated regulation of insulin secretion by pancreatic beta cells. This is primarily mediated by glucose itself, but other nutrients, including free fatty acids (FFAs), potentiate the insulinotropic capacity of glucose. A decade ago, the seven-transmembrane domain receptor (7TMR) GPR40 was demonstrated to be predominantly expressed in beta cells and activated by long-chain FFAs. This discovery added a new dimension to our understanding of FFA-mediated control of glucose homeostasis. Furthermore, GPR40 has drawn considerable interest as a novel therapeutic target to enhance insulin secretion in type 2 diabetes.