scholarly journals Novel Effects of the Gastrointestinal Hormone Secretin on Cardiac Metabolism and Renal Function

2021 ◽  
Author(s):  
Sanna Laurila ◽  
Eleni Rebelos ◽  
Minna Lahesmaa ◽  
Lihua Sun ◽  
Katharina Schnabl ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Renal Clearance ◽  
Gastrointestinal Hormones ◽  
Cardiac Metabolism ◽  
Drug Candidate ◽  
Gastrointestinal Hormone ◽  
Future Studies ◽  
Myocardial Glucose Uptake ◽  
Heart Work ◽  
Positron Emission

The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared to placebo (secretin vs. placebo, mean + standard deviation, 15.5 + 7.4 vs. 9.7 + 4.9 μmol/100g/min, 95% confidence interval (CI) [2.2, 9.4], p=0.004). Secretin also increased [18F]FDG renal clearance (44.5 + 5.4 vs. 39.5 + 8.5 ml/min, 95%CI[1.9, 8.1], p=0.004) and eGFR was significantly increased from baseline after secretin, compared to placebo (17.8 + 9.8 vs. 6.0 + 5.2 Δml/min/1.73m2, 95%CI[6.0, 17.6], p=0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.

scholarly journals Noninvasive Detection of Early Metabolic Left Ventricular Remodeling in Systemic Hypertension

Cardiology ◽  
2015 ◽  
Vol 133 (3) ◽  
pp. 157-162 ◽  
Author(s):  
Yasmin S. Hamirani ◽  
Bijoy K. Kundu ◽  
Min Zhong ◽  
Andrew McBride ◽  
Yinlin Li ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Pressure Overload ◽  
Positron Emission Tomography Imaging ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
Myocardial Glucose Uptake ◽  
Positron Emission ◽  
Metabolic Remodeling

Objectives: Hypertension (HTN) is a common cause of left ventricular hypertrophy (LVH). Sustained pressure overload induces a permanent myocardial switch from fatty-acid to glucose metabolism. In this study, we tested the hypothesis that metabolic remodeling, characterized by increased myocardial glucose uptake, precedes structural and functional remodeling in HTN-induced LVH. Methods: We recruited 31 patients: 11 with HTN only, 9 with HTN and LVH and 11 normotensive controls without LVH. Transthoracic echocardiography was performed to assess the function, mass, wall thickness and diastolic function of the left ventricle. Positron emission tomography imaging was performed, and the rate of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake, Ki, was determined using a 3-compartment kinetic model. Results: The mean Ki values were significantly higher in HTN patients than in those with HTN and LVH (p < 0.001) and in controls (p = 0.003). The unexpected decrease in Ki with LVH may be secondary to a decreased Ki with diastolic dysfunction (DD), 0.039 ± 0.032 versus 0.072 ± 0.013 (p = 0.004). There was also a significant stepwise decrease in Ki with increasing DD grade (p = 0.04). Conclusion: Glucose metabolic remodeling is detectable in hypertensive patients before the development of LVH. Furthermore, lower glucose uptake rates are observed in patients with DD. The mechanism for this last finding requires further investigation.

scholarly journals Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321774312 ◽  
Author(s):  
Mona S. Hansen ◽  
Asger Andersen ◽  
Lars P. Tolbod ◽  
Nils H. Hansson ◽  
Roni Nielsen ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Cardiac Function ◽  
Right Ventricular ◽  
Glucose Uptake ◽  
Myocardial Oxygen Consumption ◽  
External Work ◽  
Myocardial Glucose Uptake ◽  
Positron Emission ◽  
Myocardial Efficiency ◽  
Rv Function

Levosimendan is an inotropic and vasodilator drug, which is known to improve cardiac function in animal models of right ventricular (RV) failure. The effects of levosimendan on oxygen consumption and myocardial efficiency in the failing RV is unknown. We investigated the effects of levosimendan on RV function, myocardial oxygen consumption, myocardial external efficiency (MEE), and myocardial metabolism in rats with RV hypertrophy and failure. RV hypertrophy and failure were induced by pulmonary trunk banding in rats. Rats were randomized to seven weeks of treatment with vehicle (n = 16) or levosimendan (3 mg/kg/day) (n = 13). Control animals without pulmonary banding received vehicle treatment (n = 11). RV MEE and RV metabolism were evaluated by echocardiography, 11C-acetate positron emission tomography (PET), 18F-FDG PET, and invasive pressure measurements. We found that levosimendan improved RV MEE (26 ± 3 vs. 14 ± 1%, P < 0.01) by increasing RV external work (0.62 ± 0.06 vs. 0.30 ± 0.03 mmHgċmL, P < 0.001) without affecting RV myocardial oxygen consumption ( P = 0.64). The improvement in RV MEE was not associated with a change in RV myocardial glucose uptake (1.3 ± 0.1 vs. 1.0 ± 0.1 µmol/g/min, P = 0.44). In conclusion, in the hypertrophic and failing RV of the rat, levosimendan improves RV function without increasing myocardial oxygen consumption leading to improved MEE. The improvement in RV MEE was not associated with a change in myocardial glucose uptake. This study emphasizes the potential therapeutic value of chronic levosimendan treatment RV failure. It extends previous observations on the effect profile of levosimendan and motivates clinical testing of levosimendan in RV failure.

Inhibition of myocardial glucose uptake by cGMP

1998 ◽  
Vol 274 (5) ◽  
pp. H1443-H1449 ◽  
Author(s):  
Christophe Depre ◽  
Vinciane Gaussin ◽  
Sylvie Ponchaut ◽  
Yvan Fischer ◽  
Jean-Louis Vanoverschelde ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Acid Oxidation ◽  
No Production ◽  
Heart Metabolism ◽  
No Donor ◽  
Myocardial Glucose Uptake ◽  
Cyclic Monophosphate ◽  
Heart Work ◽  
Cgmp Analog

Guanosine 3′,5′-cyclic monophosphate (cGMP), a second messenger of nitric oxide (NO), regulates myocardial contractility. It is not known whether this effect is accompanied by a change in heart metabolism. We report here the effects of 8-bromoguanosine 3′,5′-cyclic monophosphate (8-BrcGMP), a cGMP analog, on regulatory steps of glucose metabolism in isolated working rat hearts perfused with glucose as the substrate. When glucose uptake was stimulated by increasing the workload, addition of the cGMP analog totally suppressed this stimulation and accelerated net glycogen breakdown. 8-BrcGMP did not affect pyruvate dehydrogenase activity but activated acetyl-CoA carboxylase, the enzyme that produces malonyl-CoA, an inhibitor of long-chain fatty acid oxidation. To test whether glucose metabolism could also be affected by altering the intracellular concentration of cGMP, we perfused hearts with N G-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, or with S-nitroso- N-acetylpenicillamine (SNAP), a NO donor. Perfusion withl-NAME decreased cGMP and increased glucose uptake by 30%, whereas perfusion with SNAP resulted in opposite effects. None of these conditions affected adenosine 3′,5′-cyclic monophosphate concentration. Limitation of glucose uptake by SNAP or 8-BrcGMP decreased heart work, and this was reversed by adding alternative oxidizable substrates (pyruvate, β-hydroxybutyrate) together with glucose. Therefore, increased NO production decreases myocardial glucose utilization and limits heart work. This effect is mediated by cGMP, which is thus endowed with both physiological and metabolic properties.

Lumped constant for deoxyglucose is decreased when myocardial glucose uptake is enhanced

1999 ◽  
Vol 276 (1) ◽  
pp. H129-H133 ◽  
Author(s):  
Katsuji Hashimoto ◽  
Tsunehiko Nishimura ◽  
Ken-Ichi Imahashi ◽  
Hitoshi Yamaguchi ◽  
Masatsugu Hori ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Accumulation Rate ◽  
Myocardial Glucose Uptake ◽  
Positron Emission ◽  
Rat Hearts ◽  
Lumped Constant ◽  
Perfused Rat Hearts ◽  
The Difference ◽  
Sugar Phosphates ◽  
Isolated Perfused Rat Hearts

Quantification of myocardial glucose uptake by positron emission tomography with [18F]fluorodeoxyglucose (FDG) requires the “lumped constant” (LC), which corrects the difference of affinity between glucose and FDG to glucose transporters and phosphorylating system. Since LC was introduced, it has been considered to be constant. However, this has recently been questioned. To elucidate the constancy of LC by other than radioisotope techniques, the accumulation rate of sugar phosphates (d[SP]/d t) was measured in isolated, perfused rat hearts by31P NMR spectroscopy with 2-deoxyglucose (DG). We postulate α as the affinity of DG to transporters and the phosphorylating system relative to that of glucose. Theoretically, α is equivalent to LC. We determined α by measuring d[SP]/d t at DG concentration ([DG]) = 10, 7, 5, and 3 mmol/l, keeping the total of glucose concentration ([glucose]) and [DG] to 10 mmol/l. When the glucose uptake was enhanced by insulin (10 mU/ml) or stunning, calculated α was reduced (insulin stimulated, 0.15; stunning, 0.19) compared with the control (0.59). These results indicate that LC can be evaluated by methods without radiolabeled tracers and is smaller when glucose uptake is augmented.

Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation against chronic hypoxia

1995 ◽  
Vol 79 (1) ◽  
pp. 222-228 ◽  
Author(s):  
J. E. Holden ◽  
C. K. Stone ◽  
C. M. Clark ◽  
W. D. Brown ◽  
R. J. Nickles ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Chronic Hypoxia ◽  
Plasma Catecholamines ◽  
Cardiac Metabolism ◽  
Metabolic Adaptation ◽  
Positive Correlation ◽  
Glucose Levels ◽  
Positron Emission ◽  
Uptake Rates ◽  
Low Altitude

The metabolism of glucose in mammalian heart is 25–50% more O2 efficient than the metabolism of free fatty acids. To assess the role of substrate preference in adaptations to chronic hypoxia, positron emission tomographic measurements of heart regional glucose uptake rates after an overnight fast were made in volunteer Quechua subjects and in Sherpa subjects, both indigenous to altitudes of over 3,000 m, and in a group of lowlander volunteers. Highest uptake rates were found in the Quechuas on arrival and in the Sherpas after a 3-wk period at low altitude, intermediate rates in Quechuas after a 3-wk period at low altitude and in the lowlanders, and lowest rates in Sherpas on arrival. These low values were probably related to the stress of travel to the site of the experiments. Measured plasma catecholamines, hormones, and substrates indicated that glucose concentrations correlated best with observed variations in glucose uptake, with a negative correlation for the control subjects and a positive correlation for the Quechuas and Sherpas. Uptake values in Quechuas declined significantly after a 3-wk period at low altitude, but the positive correlation with glucose levels persisted. We conclude that an elevated glucose preference in heart is a true metabolic adaptation in humans adapted over generations to chronic hypoxia.

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