Type 2 diabetes disrupts circadian orchestration of lipid metabolism and membrane fluidity in human pancreatic islets

Recent evidence suggests that circadian clocks ensure temporal orchestration of lipid homeostasis and play a role in pathophysiology of metabolic diseases in humans, including type 2 diabetes (T2D). Nevertheless, circadian regulation of lipid metabolism in human pancreatic islets has not been explored. Employing lipidomic analyses, we conducted temporal profiling in human pancreatic islets derived from 10 nondiabetic (ND) and 6 T2D donors. Among 329 detected lipid species across 8 major lipid classes, 5% exhibited circadian rhythmicity in ND human islets synchronized in vitro. Two-time point-based lipidomic analyses in T2D human islets revealed global and temporal alterations in phospho- and sphingolipids. Key enzymes regulating turnover of sphingolipids were rhythmically expressed in ND islets and exhibited altered levels in ND islets bearing disrupted clocks and in T2D islets. Strikingly, cellular membrane fluidity, measured by a Nile Red derivative NR12S, was reduced in plasma membrane of T2D diabetic human islets, in ND donors’ islets with disrupted circadian clockwork, or treated with sphingolipid pathway modulators. Moreover, inhibiting the glycosphingolipid biosynthesis led to strong reduction of insulin secretion triggered by glucose or KCl, whereas inhibiting earlier steps of de novo ceramide synthesis resulted in milder inhibitory effect on insulin secretion by ND islets. Our data suggest that circadian clocks operative in human pancreatic islets are required for temporal orchestration of lipid homeostasis, and that perturbation of temporal regulation of the islet lipid metabolism upon T2D leads to altered insulin secretion and membrane fluidity. These phenotypes were recapitulated in ND islets bearing disrupted clocks.

A study of circadian regulation of lipid metabolism in human pancreatic islets reveals that Type 2 Diabetes leads to global and temporal alterations of phospholipid and sphingolipid metabolism in islets, resulting in decreased membrane fluidity and insulin secretion defects.     

Die Teilung der Proplastiden und Chloroplasten beiAgapanthus umbellatus l'Hérit

Ohne Zusammenfassung     

Physiologisch-chemische Untersuchungen an der Haut nach Bestrahlung mit ultraviolettem Licht

Zusammenfassung Untersuchungen über Histamin und einen pharmakologisch histaminähnlichen Stoff ergaben für Säugetiergewebe (Mäusehaut) die papierelektrophoretische Abtrennung einer Histaminfraktion, die weder in normaler Froschhaut noch nach Bestrahlung der Tiere mit UV nachgewiesen werden konnte.Untersuchungen an Froschlunge und -muskel konnten jedoch wahrscheinlich machen, daß auch der Frosch Histamin bilden kann Es wurde gezeigt, daß ein pharmakologisch histaminähnlicher, aus alkoholischen und wäßrigen Froschhautextrakten abzutrennender Stoff nicht mit dem Histamin identisch ist. Es handelt sich um einen Indolkörper, wahrscheinlich ein Oxytryptamin, das möglicherweise mit dem 5-Oxytryptamin=Enteramin identisch ist. Der Gehalt dieses Stoffes nimmt nach längerer Bestrahlung der Tiere sehr stark ab, was als strahlenchemischer Abbau erklärt werden konnte. Eine Neubildung dieser histaminähnlichen Substanz durch eine Bestrahlung ist ausgeschlossen.Früher (nach 6stündiger Bestrahlung) als die nachgewiesenen chemischen Veränderungen (Abnahme des aktiven Hautstoffes) konnten die Folgen von Permeabilitätsänderungen festgestellt werden. Es wurde ein vermehrter Kaliumaustritt (statistisch gesichert) als Folge der Bestrahlung nachgewiesen, dem bei der Bestrahlung lebender Frösche und anschließender Untersuchung der Haut ein vermehrter Natrium und Calciumaustritt (ebenfalls statistisch gesichert) parallel ging, während dies bei der Untersuchung überlebender Haut nicht der Fall war, sondern für Calcium eher eine verminderte Abgabe angedeutet war.Meinem hochverehrten Lehrer, Herrn Prof. Dr.Giersberg, möchte ich hier ganz besonders für die Stellung des Themas sowie für seine freundliche Unterstützung bei der Durchführung der Arbeit danken.     

A window into fungal endophytism in Salicornia europaea: deciphering fungal characteristics as plant growth promoting agents

Plant and Soil - Plant-endophytic associations exist only when equilibrium is maintained between both partners. This study analyses the properties of endophytic fungi inhabiting a halophyte growing...     

Hebeloma vesterholtii, a new species in section Theobromina

The species Hebeloma vesterholtii spec. nov. is described. It is morphologically and molecularly closely related to Hebeloma theobrominum from which it can be distinguished using either morphological or molecular characters. Both of these species belong to section Theobromina. The new species is known from 13 collections from six European countries.     

Pseudotype Formation of Moloney Murine Leukemia Virus with Sendai Virus Glycoprotein F

Mixed infection of cells with both Moloney murine leukemia virus (MoMLV) and related or heterologous viruses produces progeny pseudotype virions bearing the MoMLV genome encapsulated by the envelope of the other virus. In this study, pseudotype formation between MoMLV and the prototype parainfluenza virus Sendai virus (SV) was investigated. We report for the first time that SV infection of MoMLV producer cells results in the formation of MoMLV(SV) pseudotypes, which display a largely extended host range compared to that of MoMLV particles. This could be associated with SV hemagglutinin-neuraminidase (SV-HN) glycoprotein incorporation into MoMLV envelopes. In contrast, solitary incorporation of the other SV glycoprotein, SV fusion protein (SV-F), resulted in a distinct and narrow extension of the MoMLV host range to asialoglycoprotein receptor (ASGP-R)-positive cells (e.g., cultured human hepatoma cells). Since stably ASGP-R cDNA-transfected MDCK cells, but not parental ASGP-R-negative MDCK cells, were found to be transduced by MoMLV(SV-F) pseudotypes and transduction of ASGP-R-expressing cells was found to be inhibited by ASGP-R antiserum, a direct proof for the ASGP-R-restricted tropism of MoMLV(SV-F) pseudotypes was provided. Cultivation of ASGP-R-positive HepG2 hepatoma cells on Transwell-COL membranes led to a significant enhancement of MoMLV(SV-F) titers in subsequent flowthrough transduction experiments, thereby suggesting the importance of ASGP-R accessibility at the basolateral domain for MoMLV(SV-F) pseudotype transduction. The availability of such ASGP-R-restricted MoMLV(SV-F)-pseudotyped vectors opens up new perspectives for future liver-restricted therapeutic gene transfer applications.