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Furthermore, both Fsp27 deficient and Fsp27/leptin double deficient mice display improved insulin sensitivity and a lean phenotype.
Finally, and compatibly with their CR phenotype, Eps8KO mice display improved metabolic status, which is the most likely cause of their increased lifespan.
Indeed, under HFD, JWH-133-treated WT mice show enhanced insulin resistance and fat inflammation, whereas Cnr2 −/− mice display improved insulin sensitivity and reduced fat inflammation.
However, fetuin-A might exert more functions: several studies demonstrated that fetuin-A can act as a natural inhibitor of the insulin receptor tyrosine kinase in liver and skeletal muscle [3] [7], and fetuin-A knockout mice display improved insulin sensitivity and are resistant to weight gain upon a high-fat diet [8].
Supporting this, we reported that diet-induced obese Nck1 −/− mice display improved overall glucose homeostasis and enhanced hepatic insulin signaling that correlates with reduced UPR compared to obese Nck1 +/+ littermates [ 24].
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KRAP−/− mice displayed improved glucose tolerance with lower insulin levels compared with wild-type mice (Figure 5A, 5B), suggesting the possibility that peripheral insulin sensitivity and/or insulin-independent glucose uptake is enhanced in KRAP−/− mice.
In line with our results, this study found that Hq mice displayed improved glucose tolerance associated with reduced fasting and glucose-induced insulin secretion, possibly due to the improved insulin sensitivity.
Remarkably, these mice displayed improved glucose tolerance due to enhanced insulin exocytosis from pancreatic β cells.
Compared to non-Tg littermates, hearts from Tg mice displayed improved membrane integrity (38 ± 14% lower lactate dehydrogenase release), while sustaining normal cardiac work.
Consistently, insulin sensitivity and secretion was not changed in p21−/− mice under chow diet, but these mice displayed improved insulin resistance under high fat high sucrose (HFHS) diet when compared to WT mice (Inoue et al, 2008).
Examined at ages up to 12 wk, Ins1LKB1KO mice displayed improved glucose tolerance (Fig. 1 A ), unaltered insulin sensitivity (Fig. 1 B), and sharply improved in vivo insulin secretion (Fig. 1 C) compared to WT littermates.
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