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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes

Mardinoglu, Adil, 1982 (author)
KTH,Science for Life Laboratory, SciLifeLab
Gogg, Silvia, 1962 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Lotta, L. A. (author)
University Of Cambridge
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Stancakova, A. (author)
Nerstedt, Annika, 1960 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Borén, Jan, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Bluher, M. (author)
Universität Leipzig,Leipzig University
Ferrannini, E. (author)
Langenberg, C. (author)
University Of Cambridge
Wareham, N. J. (author)
University Of Cambridge
Laakso, M. (author)
Itä-Suomen Yliopisto,University of Eastern Finland
Smith, Ulf, 1943 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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 (creator_code:org_t)
Elsevier BV, 2018
2018
English.
In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 27, s. 151-155
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

3-Hydroxyisobutyric acid (3-HIB)
Branched-chain amino acids (BCAAs)
T2D
Insulin resistance
Insulin
insulin sensitivity
glucose-tolerance
cardiovascular-disease
metabolic signature
mannose levels
resistance
obesity
risk
General & Internal Medicine
Research & Experimental Medicine
Insulin secretion

Publication and Content Type

ref (subject category)
art (subject category)

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