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Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors. Identified targets, alongside ATP binding cassette transporter A1 (ABCA1) (included control) were silenced in the same cells, and insulin secretion (ELISA) and mitochondrial metabolism (seahorse) were assessed with/without ApoA-I priming. Human β-cell expression data was used to investigate ApoA-I receptor pathways in type 2 diabetes (T2D). Scavenger receptor B1 (SR-BI) and regulator of microtubule dynamics 1 were identified as ApoA-I targets. SR-BI or ABCA1 silencing abolished ApoA-I induced increases in insulin secretion. ApoA-I priming increased mitochondrial OXPHOS, however this was greatly attenuated with SR-BI or ABCA1 silencing. Supporting this, human β-cell expression data investigations found SR-BI and ABCA1 to be correlated with genes associated with mitochondrial pathways. In all, SR-BI and ABCA1 correlated with 73 and 3 genes differentially expressed in T2D, respectively. We confirm that SR-BI and ABCA1 are the primary β-cell ApoA-I receptors and demonstrate that ApoA-I priming enhances β-cell insulin secretion via the upregulation of mitochondrial metabolism through ApoA-I-SR-BI and ApoA-I-ABCA1 pathways. We propose that SR-BI relies on mitochondrial and exocytotic pathways, while ABCA1 depends solely on mitochondrial pathways. Our findings uncover new targets in ApoA-I β-cell mechanism for T2D therapies. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic [beta] cells. To identify candidate genes contributing to T2D pathophysiology, we studied human pancreatic islets from approximately 300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified expression changes in islets may predispose to diabetes, as expression of these genes associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human [beta] cells, based on single-cell RNA-Seq data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D SNPs. Mouse KO strains demonstrated that the identified T2D-associated candidate genes regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing [beta] cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we have identified molecular alterations in human pancreatic islets that contribute to [beta] cell dysfunction in T2D pathophysiology., Introduction Type 2 diabetes (T2D) is characterized by chronic hyperglycemia due to insufficient insulin secretion from pancreatic islets, often in combination with insulin resistance in target cells. The number of [...]

Two Roman objects in the J. Paul Getty Museum, a bronze statuette of the moon goddess Luna and a cornelian gem were among the handful of classical antiquities purchased for Adolf Hitler's unrealized "Führermuseum" in Linz. This study presents new provenance research that tracks their itineraries from European private collections to the gallery of Kurt Walter Bachstitz, a prominent Jewish art dealer active in The Hague between the 1920s and the 1940s. His precarious personal and business relationships with German art agents expose how ordinary commerce was entangled with coerced sales in the Nazioccupied Netherlands. Informed by debates over the status of works that had changed hands on wartime art markets, in 2015 the Dutch Restitution Committee recommended that the gem be returned to Bachstitz's heirs but rejected their claim for the statuette. Having passed through various collections following their restitution after World War II, the two objects were reunited at the Getty in 2017. [ABSTRACT FROM AUTHOR]

When the invention of le daguerreotype was announced in Paris in January 1839, it was immediately acclaimed for its astonishing ability to replicate 'the finest monuments and ... most delightful [...]

Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review. [ABSTRACT FROM AUTHOR]

Cemeteries that encircled the Campanian town of Nola furnished many of the ancient vases most highly sought after by eighteenth-century collectors. Attracted by the exceptional quality of the glazes on what was later recognized as Attic pottery, antiquaries looked to the figured scenes for reflections of lost masterpieces of ancient Greek painting. Enmeshed practices of connoisseurship, scholarship and commerce were already firmly in place by the 1740S. Comparing vases to Old Master drawings and adopting modes of display popular for Continental Porzellan-kabinetten, collectors relocated Greek vase painting from the realm of curiosity to that of fine art. [ABSTRACT FROM AUTHOR]

This study reconstructs the private museum of 400 ancient vases and other classical antiquities owned by Felice Maria Mastrilli and displayed in the Palazzo di San Nicandro in Naples. The collection, formed between 1740 and 1755 through purchases and excavations conducted on family properties in Nola, was dispersed following Mastrilli's death. A number of the identifiable vases mere acquired Sir William Hamilton and illuminate his role in encouraging the reception of a Neo-Classical aesthetic. On the basis of archival documents and an extensive set of unpublished drawings, the original display narrative programme and iconographic interpretations of the vases arc analyzed. The 'Museo Mastrilli' is assessed within the local Neapolitan context of antiquarian scholarship and amateur cabinets of the first half of the eighteen century, a period that witnessed the first scholarly publications of vases, early attempts to systematize their figural representations and the emergency of a rigorous market in black-and red-figured pottery. [ABSTRACT FROM AUTHOR]

Nutritional status provides metabolic substrates to activate AMP-Activated Protein Kinase (AMPK), the energy sensor that regulates metabolism. Recent evidence has demonstrated that AMPK has wider functions with respect to regulating immune cell metabolism and function. One such example is the regulatory role that AMPK has on NLRP3-inlflammasome and IL-1β biology. This in turn can result in subsequent negative downstream effects on glucose, lipid and insulin metabolism. Nutrient stress in the form of obesity can impact AMPK and whole-body metabolism, leading to complications such as type 2 diabetes and cancer risk. There is a lack of data regarding the nature and extent that nutrient status has on AMPK and metabolic-inflammation. However, emerging work elucidates to a direct role of individual nutrients on AMPK and metabolic-inflammation, as a possible means of modulating AMPK activity. The posit being to use such nutritional agents to re-configure metabolic-inflammation towards more oxidative phosphorylation and promote the resolution of inflammation. The complex paradigm will be discussed within the context of if/how dietary components, nutrients including fatty acids and non-nutrient food components, such as resveratrol, berberine, curcumin and the flavonoid genistein, modulate AMPK dependent processes relating to inflammation and metabolism. [ABSTRACT FROM AUTHOR]