Will treating diabetes with 11β-HSD1 inhibitors affect the HPA axis?
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作者:
Harno, Erika
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机构:Univ Manchester, Acad Hlth Sci Ctr, Fac Life Sci, Manchester M13 9PL, Lancs, England
Harno, Erika
White, Anne
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Univ Manchester, Acad Hlth Sci Ctr, Fac Life Sci, Manchester M13 9PL, Lancs, EnglandUniv Manchester, Acad Hlth Sci Ctr, Fac Life Sci, Manchester M13 9PL, Lancs, England
White, Anne
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机构:
[1] Univ Manchester, Acad Hlth Sci Ctr, Fac Life Sci, Manchester M13 9PL, Lancs, England
Inhibitors of 11 beta-HSD1 are in clinical trials for the treatment of type 2 diabetes. These compounds act by decreasing the cortisol generated in liver and adipose tissue, and therefore reducing tissue-specific gluconeogenesis and fatty acid metabolism. However, there is concern that reduction in tissue-regenerated cortisol might decrease feedback to the hypothalamic-pituitary-adrenal (HPA) axis, resulting in upregulation of cortisol from the adrenal gland. This review considers evidence from 11 beta-HSD1 knockout and transgenic mice, inhibitor studies and results from clinical trials evaluating HPA axis biomarkers. It is clear that analysis of the HPA axis is not sufficiently detailed, and there is a need to understand the subtle changes in the axis associated with pulsatility, diurnal rhythm and stress.
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Univ Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Harno, Erika
Cottrell, Elizabeth C.
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Univ Manchester, Fac Med & Human Sci, Ctr Endocrinol & Diabet, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Cottrell, Elizabeth C.
Yu, Alice
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AstraZeneca, CVGI iMed, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Yu, Alice
DeSchoolmeester, Joanne
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AstraZeneca, CVGI iMed, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
DeSchoolmeester, Joanne
Gutierrez, Pablo Morentin
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AstraZeneca, DMPK, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Gutierrez, Pablo Morentin
Denn, Mark
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AstraZeneca, DMPK, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Denn, Mark
Swales, John G.
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AstraZeneca, DMPK, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Swales, John G.
Goldberg, Fred W.
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AstraZeneca, CVGI iMed, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Goldberg, Fred W.
Bohlooly-Y, Mohammad
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AstraZeneca, Transgen RAD, Discovery Sci, S-43183 Molndal, SwedenUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Bohlooly-Y, Mohammad
Andersen, Harriet
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AstraZeneca, Transgen RAD, Discovery Sci, S-43183 Molndal, SwedenUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Andersen, Harriet
Wild, Martin J.
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AstraZeneca, DMPK, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Wild, Martin J.
Turnbull, Andrew V.
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AstraZeneca, CVGI iMed, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Turnbull, Andrew V.
Leighton, Brendan
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AstraZeneca, CVGI iMed, Alderley Pk SK10 4TG, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Leighton, Brendan
White, Anne
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Univ Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
Univ Manchester, Fac Med & Human Sci, Ctr Endocrinol & Diabet, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Fac Life Sci, Neurosci Res Grp, Manchester M13 9PT, Lancs, England
机构:
Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Fang, Chu-Hong
Li, Yu-Peng
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Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Li, Yu-Peng
Li, Ying
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Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Li, Ying
Yue, Jian-Min
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Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Yue, Jian-Min
Bao, Jie
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Univ Jinan, Sch Biol Sci & Technol, 336 West Rd Nan Xinzhuang, Jinan 250022, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
Bao, Jie
Yu, Jin-Hai
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Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R ChinaBohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China