Institution
Eli Lilly and Company
Company•Indianapolis, Indiana, United States•
About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.
Topics: Population, Agonist, Insulin, Placebo, Olanzapine
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TL;DR: Using quantitative real-time polymerase chain reaction and parallel analysis of a carefully selected group of reference genes, the relative expression of each PDE isoenzyme across the 24 selected tissues is determined, and the expression of selected PDEs to each other within a given tissue type is compared.
376 citations
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TL;DR: The data indicate that skeletal muscle is a source of FGF21 and that its expression is regulated by a phosphatidylinosistol 3‐kinase (PI3‐kinases)/Akt1 signaling pathway‐dependent mechanism.
375 citations
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TL;DR: A diurnal rhythm was observed in the responsiveness of mice to nociceptive stimuli and in the hyperalgesic activity of endogenous opioid peptides and may partly account for previous controversy over the direct action of naloxone in opiate-naive animals.
Abstract: A diurnal rhythm was observed in the responsiveness of mice to nociceptive stimuli and in the hyperalgesic activity of endogenous opioid peptides and may partly account for previous controversy over the direct action of naloxone in opiate-naive animals.
375 citations
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TL;DR: The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here and an evaluation of intersite NMR analytical reproducibility has revealed a high degree of robustness.
375 citations
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TL;DR: It is demonstrated that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15 that mediates the metabolic effects of GDF12 and binds to GDF 15 in vitro and is required for the metabolic actions of G DF15 with respect to body weight and food intake in vivo in mice.
Abstract: Growth/differentiation factor 15 (GDF15), also known as MIC-1, is a distant member of the transforming growth factor-β (TGF-β) superfamily and has been implicated in various biological functions, including cancer cachexia, renal and heart failure, atherosclerosis and metabolism. A connection between GDF15 and body-weight regulation was initially suggested on the basis of an observation that increasing GDF15 levels in serum correlated with weight loss in individuals with advanced prostate cancer. In animal models, overexpression of GDF15 leads to a lean phenotype, hypophagia and other improvements in metabolic parameters, suggesting that recombinant GDF15 protein could potentially be used in the treatment of obesity and type 2 diabetes. However, the signaling and mechanism of action of GDF15 are poorly understood owing to the absence of a clearly identified cognate receptor. Here we report that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15. GFRAL binds to GDF15 in vitro and is required for the metabolic actions of GDF15 with respect to body weight and food intake in vivo in mice. Gfral-/- mice were refractory to the effects of recombinant human GDF15 on body-weight, food-intake and glucose parameters. Blocking the interaction between GDF15 and GFRAL with a monoclonal antibody prevented the metabolic effects of GDF15 in rats. Gfral mRNA is highly expressed in the area postrema of mouse, rat and monkey, in accordance with previous reports implicating this region of the brain in the metabolic actions of GDF15 (refs. 4,5,6). Together, our data demonstrate that GFRAL is a receptor for GDF15 that mediates the metabolic effects of GDF15.
374 citations
Authors
Showing all 17866 results
Name | H-index | Papers | Citations |
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Mark J. Daly | 204 | 763 | 304452 |
Irving L. Weissman | 201 | 1141 | 172504 |
Eric J. Topol | 193 | 1373 | 151025 |
Tony Hunter | 175 | 593 | 124726 |
Xiang Zhang | 154 | 1733 | 117576 |
Jerrold M. Olefsky | 143 | 595 | 77356 |
Stephen F. Badylak | 133 | 530 | 57083 |
George A. Bray | 131 | 896 | 100975 |
Lloyd Paul Aiello | 131 | 506 | 85550 |
Levi A. Garraway | 129 | 366 | 99989 |
Mark Sullivan | 126 | 802 | 63916 |
James A. Russell | 124 | 1024 | 87929 |
Tony L. Yaksh | 123 | 806 | 60898 |
Elisabetta Dejana | 122 | 430 | 48254 |
Hagop S. Akiskal | 118 | 565 | 50869 |