Liver-Specific Overexpression of Prostasin Attenuates High-Fat Diet-Induced Metabolic Dysregulation in Mice

The liver has a most indispensable role in glucose and lipid metabolism where we see some of the most serious worldwide health problems. The serine protease prostasin (PRSS8) cleaves toll-like receptor 4 (TLR4) and regulates hepatic insulin sensitivity under PRSS8 knockout condition. However, liver substrate proteins of PRSS8 other than TLR4 and the effect to glucose and lipid metabolism remain unclarified with hepatic elevation of PRSS8 expression. Here we show that high-fat-diet-fed liver-specific PRSS8 transgenic mice improved glucose tolerance and hepatic steatosis independent of body weight. PRSS8 amplified extracellular signal-regulated kinase phosphorylation associated with matrix metalloproteinase 14 activation in vivo and in vitro. Moreover, in humans, serum PRSS8 levels reduced more in type 2 diabetes mellitus (T2DM) patients than healthy controls and were lower in T2DM patients with increased maximum carotid artery intima media thickness (>1.1 mm). These results identify the regulatory mechanisms of PRSS8 overexpression over glucose and lipid metabolism, as well as excessive hepatic fat storage

White Polymer Light-Emitting Electrochemical Cells Fabricated Using Energy Donor and Acceptor Fluorescent π‑Conjugated Polymers Based on Concepts of Band-Structure Engineering

The authors report on white polymer light-emitting electrochemical cells (PLECs) fabricated with a polymer blend film composed of a blue fluorescent π-conjugated polymer (blue FCP), poly­(9,9-di-<i>n</i>-dodecyl­fluorenyl-2,7-diyl) (PFD), and a red-orange FCP, poly­[2-methoxy-5-(2′-ethyl­hexyloxy)-1,4-phenylene­vinylene] (MEH-PPV), based on concepts of band-structure engineering. Polymer blending is one of the simplest and most promising methods for fabrication of van der Waals interfaces, which convert electricity to light in PLECs. By optimizing the composition of PFD, MEH-PPV, poly­(ethylene oxide) (PEO), and salt (KCF₃SO₃) in the active layer, white-light emission with Commission Internationale de l’Eclairage (CIE) coordinates of (<i>x</i> = 0.33, <i>y</i> = 0.31) can be achieved through light mixing of blue exciton emission from PFD and red-orange exciton emission from MEH-PPV at an applied voltage higher than the threshold voltage, <i>V</i>_th^blue‑FCP, which corresponds to <i>E</i>_g^blue‑FCP/<i>e</i>, where <i>E</i>_g^blue‑FCP is the band gap of PFD and <i>e</i> is the elemental charge. The white light produced by light mixing of PFD and MEH-PPV emissions can be obtained at a low MEH-PPV concentration, while only red-orange emissions from MEH-PPV are obtained at high MEH-PPV concentrations. The emission color of FCP-blend PLECs can be explained by Förster resonance energy transfer (FRET) from the excited PFD to the MEH-PPV because the photoluminescence (PL) spectrum of PFD overlaps with the UV–vis absorption spectrum of MEH-PPV. However, FRET was limited by the presence of PEO in the active layers of the FCP-blend PLECs. This meant it was much easier to tune the emission colors compared to FCP-blend polymer light-emitting diodes (PLEDs), in which FRET occurs predominantly. Utilization of a polymer blend film of blue and red-orange FCPs in PLECs is a very effective and promising method for fabrication of white light-emitting devices

Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG) protein in fulminant type 1 diabetes.

BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG) Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells

Cell-cell interaction between acinar-like cells and islet endocrine cells encapsulated by common BMs.

<p><b>A:</b> A desmosomal junction (arrowhead) is observed between acinar-like cells (AC) and alpha cells (A), which are encapsulated by common BMs and ECM. <b>B</b>: Coated-pit-like structure is observed between an acinar-like cell (AC) and an alpha cell (A) touching directly and covered by common BMs (arrows). Inset shows a magnified view of the coated-pit-like structure. <b>C</b>: Excretion of vesicles from acinar-like cells (AC) to a beta cell (B). Note the vesicular membrane of the AC is dissolved (arrow), and the vesicular content is released to the beta cell (B) touching it. <b>D1</b>: Exocytotic features of vesicles in acinar-like cells (AC) to beta cells (B), which are in contact with each other. Arrowhead indicates BMs/ECM encapsulating acinar-like cells and beta cells, V: vasculature. <b>D2:</b> Higher magnified view of D1. The vesicle is internalized to the beta cell. AC: acinar-like cell, B: beta cell. <b>E:</b> Vesicles of acinar-like cells (AC) are internalized to touching alpha cells (A) and beta cell (B) shown by arrows. Arrowheads indicate BMs/ECM surrounding beta cell (B), alpha cell (A), and acinar-like cell (AC). Inset shows magnified view of (E). LB: lipofuscin body, ER: endoplasmic reticulum.</p