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| 12. |
- Parker, Victoria E. R., et al.
(författare)
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Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5, s. 2086-2093
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Tidskriftsartikel (refereegranskat)abstract
- Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994. In a two-part randomized phase 2a trial in men and women with overweight or obesity and type 2 diabetes mellitus, cotadutide promoted greater reductions in liver glycogen and fat than placebo and liraglutide.
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| 13. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 14. |
- Wengelin, Åsa, et al.
(författare)
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Combined eyetracking and keystroke-logging methods for studying cognitive processes in text production
- 2009
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Ingår i: Behavior Research Methods. - New York : Springer-Verlag New York. - 1554-351X .- 1554-3528. ; 41:2, s. 337-351
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Tidskriftsartikel (refereegranskat)abstract
- Writers typically spend a certain proportion of time looking back over the text that they have written. This is likely to serve a number of different functions, which are currently poorly understood. In this article, we present two systems, ScriptLog + TimeLine and EyeWrite, that adopt different and complementary approaches to exploring this activity by collecting and analyzing combined eye movement and keystroke data from writers composing extended texts. ScriptLog + TimeLine is a system that is based on an existing keystroke-logging program and uses heuristic, pattern-matching methods to identify reading episodes within eye movement data. EyeWrite is an integrated editor and analysis system that permits identification of the words that the writer fixates and their location within the developing text. We demonstrate how the methods instantiated within these systems can be used to make sense of the large amount of data generated by eyetracking and keystroke logging in order to inform understanding of the cognitive processes that underlie written text production.
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