2006 - Institut für Klinische Chemie - UniversitätsSpital Zürich

Universität Zürich > Medizinische Fakultät > Klinische Chemie, Institut für > Prof. Dr.
Arnold von Eckardstein
Do lipoproteins modulate pancreatic beta-cell survival and function?
Summary / Zusammenfassung
Numerous clinical and epidemiological studies have demonstrated the associations of
hypertriglyceridemia (i.e. increased aounts of very low density lipoproteins = VLDL), low high
density lipoprotein (HDL) cholesterol and the presence of small dense low density lipoproteins
(LDL) with increased risk of future type 2 diabetes mellitus. Traditionally these dyslipidemias
have been considered as indirect confounders of insulin resistance, i.e. the immediate precursor of
diabetes mellitus type 2. More recent data, however, showed that lipoproteins exert biological
functions beyond lipid transport, for example regulation of cell proliferation and cell death. Initial
results indicate that VLDL and LDL exert pro-apoptotic effects on beta cells which are
counteracted by HDL. In this line we, i.e. two laboratories with long standing histories in either
lipoprotein and atherosclerosis research (A.v.E.) or diabetes research (M.D.), wish to collaborate
and to answer the following two questions: 1. What are the effects of VLDL, different LDL size
classes and HDL on beta cell survival, proliferation and function and do these lipoproteins
modulate the adverse effects of cytokines, leptin, saturated fatty acids and high glucose? 2. Which
molecular components are responsible for the putative beneficial effects of HDL on beta-cell
turnover and secretory function? To answer these questions a PhD student will perform a series of
experiments in primary human and murine beta cells, to monitor the effects of native lipoproteins
and isolated protein and lipid components thereof on apoptosis, cell proliferation, insulin
production and secretion, and protein kinase B (Akt) activity. The elucidation of lipoprotein effects
on beta cell function and survival may open new avenues to the introduction of treatment
modalities aimed to prevent or delay the manifestation of diabetes mellitus.
Publications / Publikationen
Rohrer, L, Hersberger, M, von Eckardstein A (2004). High density lipoproteins in the intersection
of diabetes mellitus, inflammation and cardiovascular d˛sease. Curr. Opin. Lipidol. 15, 269-278
Donath MY, Halban PA (2004). Decreased beta cell mass in type 2 diabetes: significance,
mechanisms and therapeutic implications. DIabetologia 47: 581-589
Keywords / Suchbegriffe
HDL, diabetes, beta cells
Project Leadership and Contacts / Projektleitung und Kontakte
Prof. Marc Donath (Project Leader) marc.donath@usz.ch
Prof. Arnold von Eckardstein (Project Leader) arnold.voneckardstein@usz.ch
Dr. Lucia Rohrer lucia.rohrer@usz.ch
Funding Source(s) / Unterstützt durch
Nachwuchsförderungskredit der Universität Zürich, Foundation
Novartis Foundation and Center of Integrated Human Physiology
Project 6030
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