PMID- 23047828 OWN - NLM STAT- MEDLINE DCOM- 20130903 LR - 20221207 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 45 IP - 2 DP - 2013 Feb TI - Circulating very-low-density lipoprotein from subjects with impaired glucose tolerance accelerates adrenocortical cortisol and aldosterone synthesis. PG - 169-72 LID - 10.1055/s-0032-1323844 [doi] AB - Apart from their role in cardiovascular homeostasis and immunomodulation, aldosterone and cortisol are also implicated in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). Furthermore, glycoxidative modifications of lipoproteins are increasingly recognized as an etiological factor for increased cardiovascular morbidity and mortality in prediabetic individuals. The causative relationship between in vivo lipoprotein modifications and steroidogenesis in subjects with impaired glucose tolerance (IGT), however, is not well defined. Therefore, we aimed to investigate the impact of in vivo modified lipoproteins on aldosterone and cortisol release from human adrenocortical H295R cells. Following an oral glucose tolerance test, 20 individuals with normal glucose tolerance (NGT) and 20 IGT subjects were randomly selected from the ongoing PRAEDIAS prevention study in our department. Cells were incubated for 24 h with lipoproteins isolated from NGT and IGT individuals and aldosterone and cortisol release was measured in the supernatants. VLDL induced a greater stimulating effect on adrenocortical aldosterone and cortisol release compared to HDL and LDL. Moreover, IGT-VLDL evoked a significantly higher effect (p<0.05) on hormone release than NGT-VLDL. Incubation of cells with in vitro modified lipoproteins and specific pharmacological inhibitors suggests that VLDL presumably recruits ERK1/2 as one of the downstream effectors of Jak-2. In summary, in vivo modified VLDL are able to promote prediabetic hormonal dysregulation by modulating adrenocortical steroidogenesis via Jak-2-ERK dependent pathway. CI - (c) Georg Thieme Verlag KG Stuttgart . New York. FAU - Saha, S AU - Saha S AD - Department of Internal Medicine 3, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany. FAU - Schwarz, P E H AU - Schwarz PE FAU - Bergmann, S AU - Bergmann S FAU - Bornstein, S R AU - Bornstein SR FAU - Graessler, J AU - Graessler J FAU - Kopprasch, S AU - Kopprasch S LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121009 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Glycated Hemoglobin A) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Protein Kinase Inhibitors) RN - 0 (hemoglobin A1c protein, human) RN - 4964P6T9RB (Aldosterone) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Adrenal Cortex/drug effects/*metabolism MH - Aged MH - Aldosterone/*metabolism MH - Cell Line MH - Glucose Intolerance/blood/*metabolism/physiopathology MH - Glycated Hemoglobin/analysis MH - Humans MH - Hydrocortisone/*metabolism MH - Hyperglycemia/etiology MH - Lipoproteins, HDL/blood/metabolism MH - Lipoproteins, LDL/blood/metabolism MH - Lipoproteins, VLDL/blood/*metabolism MH - MAP Kinase Signaling System/drug effects MH - Male MH - Middle Aged MH - Phosphorylation/drug effects MH - Prediabetic State/blood/metabolism/physiopathology MH - Protein Kinase Inhibitors/pharmacology MH - Protein Processing, Post-Translational/drug effects MH - *Up-Regulation/drug effects EDAT- 2012/10/11 06:00 MHDA- 2013/09/04 06:00 CRDT- 2012/10/11 06:00 PHST- 2012/10/11 06:00 [entrez] PHST- 2012/10/11 06:00 [pubmed] PHST- 2013/09/04 06:00 [medline] AID - 10.1055/s-0032-1323844 [doi] PST - ppublish SO - Horm Metab Res. 2013 Feb;45(2):169-72. doi: 10.1055/s-0032-1323844. Epub 2012 Oct 9.