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Impact of metabolic...
Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
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- Virta, J (författare)
- University of Turku
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- Silvola, J.M.U. (författare)
- University of Turku
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- Kiugel, M (författare)
- University of Turku
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- Liljenback, H (författare)
- University of Turku
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- Berglund, Lisa (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Garcia Vaz, Eliana (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Dutius Andersson, Anna-Maria (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Zetterqvist, Anna (författare)
- Lund University,Lunds universitet
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- Oikonen, V (författare)
- University of Turku
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- Jauhianen, M (författare)
- Finnish National Institute for Health and Welfare
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- Knuuti, J (författare)
- University of Turku
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- Nuutila, P (författare)
- University of Turku
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- Roivainen, A (författare)
- University of Turku
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- Gomez, Maria F (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Saraste, A (författare)
- University of Turku
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(creator_code:org_t)
- 2022-10-03
- 2022
- Engelska 1 s.
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 43:2, s. 3076-3076
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain.PurposeTo characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model.MethodsCardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET.ResultsCompared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B).ConclusionsObese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work.Funding AcknowledgementType of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Virta, J
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Silvola, J.M.U.
-
Kiugel, M
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Liljenback, H
-
Berglund, Lisa
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Garcia Vaz, Elia ...
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visa fler...
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Dutius Andersson ...
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Zetterqvist, Ann ...
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Oikonen, V
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Jauhianen, M
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Knuuti, J
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Nuutila, P
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Roivainen, A
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Gomez, Maria F
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Saraste, A
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