Chylomicron and palmitate metabolism by perfused hearts from diabetic mice. Am J Physiol Endocrinol Metab 284: E357-E365, 2003. First published October 22, 2002 10.1152/ajpendo.00380.2002 in circulating chylomicrons by endotheliumbound lipoprotein lipase (LPL) provides a source of fatty acids (FA) for cardiac metabolism. The effect of diabetes on the metabolism of chylomicrons by perfused mouse hearts was investigated with db/db (type 2) and streptozotocin (STZ)-treated (type 1) diabetic mice. Endothelium-bound heparin-releasable LPL activity was unchanged in both type 1 and type 2 diabetic hearts. The metabolism of LPL-derived FA was examined by perfusing hearts with chylomicrons containing radiolabeled TG and by measuring 3 H2O accumulation in the perfusate (oxidation) and incorporation of radioactivity into tissue TG (esterification). Rates of LPL-derived FA oxidation and esterification were increased 2.3-fold and 1.7-fold in db/db hearts. Similarly, LPL-derived FA oxidation and esterification were increased 3.4-fold and 2.5-fold, respectively, in perfused hearts from STZ-treated mice. The oxidation and esterification of [ 3 H]palmitate complexed to albumin were also increased in type 1 and type 2 diabetic hearts. Therefore, diabetes may not influence the supply of LPL-derived FA, but total FA utilization (oxidation and esterification) was enhanced. diabetic cardiomyopathy; lipoprotein lipase; fatty acid metabolism FATTY ACIDS (FA) are generally considered to be the preferred oxidative substrate for the heart (41). The two sources of FA for cardiac metabolism are 1) circulating FA bound to plasma albumin that can be taken up directly by the heart, and 2) hydrolysis of triacylglycerols (TG) in circulating lipoproteins (chylomicrons and very-low-density lipoproteins) by an endotheliumbound enzyme, lipoprotein lipase (LPL), to also yield FA for cardiac uptake and metabolism (6).Chylomicrons are the preferred lipoprotein substrate for LPL (14). Recently, chylomicron metabolism has been measured with isolated perfused working hearts from rats (15, 42) and mice (29), so that the metabolic fate of LPL-derived FA could be compared with the utilization of albumin-bound FA.Metabolism of exogenous substrates is altered markedly in diabetic hearts (26, 38). As a consequence of decreased glucose utilization and increased oxidation of albumin-bound FA by hearts from insulin-deficient (type 1) diabetic rats (35), FA oxidation becomes almost the exclusive energy source for the diabetic hearts. Similar results showing elevated FA oxidation have been reported recently for perfused working hearts from diabetic db/db mice (2), an animal model of type 2 diabetes with obesity and insulin resistance (9, 22). However, observations that FA oxidation was increased in type 1 and type 2 diabetic hearts have been obtained from perfusions with albumin-bound FA (palmitate) only (2,35,38). In the case of chylomicron metabolism, the supply of FA for the diabetic heart could be altered if endothelium-bound LPL activity is changed, in additio...
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Background: Reproducibility is a central tenant of research. Explicit reproducibility checks are made across different disciplines trying to assess the replication of previously published studies. We aimed to synthesize the literature on reproducibility and describe its epidemiological characteristics, including how reproducibility is defined and assessed. We also aimed to determine and compare estimates for reproducibility across different fields.Methods and Findings: We conducted a scoping review to identify English language replication studies published between 2018-2019 in economics, education, psychology, health sciences and biomedicine. We searched Medline, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature – CINAHL, Education Source via EBSCOHost, ERIC, EconPapers, International Bibliography of the Social Sciences (IBSS), and EconLit. Documents retrieved were screened in duplicate against our inclusion criteria. We extracted year of publication, number of authors, country of affiliation of the corresponding author, and whether the study was funded. For the individual replication studies, we recorded whether a registered protocol was used, whether there was contact between the replicating team and the original authors, what study design was used, and what the primary outcome was. Finally, we recorded how replication was defined by the authors, and whether the assessed study(ies) successfully replicated based on this definition. Extraction was done by a single reviewer and quality controlled by a second reviewer. Our search identified 11,224 unique documents, of which 47 were included in this review. Most studies were related to either psychology (48.6%) or health sciences (23.7%). Among these 47 documents, 36 described a single replication study while the remaining 11 reported at least two replications in the same paper. Less than the half of the studies referred to a registered protocol. There was variability in the definitions of replication success. In total, across the 47 documents 177 studies were reported. Based on the definition used by the author of each study, 95 of 177 (53.7%) studies replicated. Conclusion: This study gives an overview of research across five disciplines that explicitly set out to replicate previous research. Such replication studies are extremely scarce, the definition of a success in replication is ambiguous, and the replication rate is overall modest.
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