BackgroundIntracellular Na+ concentration ([Na+]i) regulates Ca2+ cycling, contractility, metabolism, and electrical stability of the heart. [Na+]i is elevated in heart failure, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na+]i is also increased in type 2 diabetes (T2D) due to enhanced activity of the Na+–glucose cotransporter.Methods and ResultsTo test this hypothesis, we used myocardial tissue from humans with T2D and a rat model of late-onset T2D (HIP rat). Western blot analysis showed increased Na+–glucose cotransporter expression in failing hearts from T2D patients compared with nondiabetic persons (by 73±13%) and in HIP rat hearts versus wild-type (WT) littermates (by 61±8%). [Na+]i was elevated in HIP rat myocytes both at rest (14.7±0.9 versus 11.4±0.7 mmol/L in WT) and during electrical stimulation (17.3±0.8 versus 15.0±0.7 mmol/L); however, the Na+/K+-pump function was similar in HIP and WT cells, suggesting that higher [Na+]i is due to enhanced Na+ entry in diabetic hearts. Indeed, Na+ influx was significantly larger in myocytes from HIP versus WT rats (1.77±0.11 versus 1.29±0.06 mmol/L per minute). Na+–glucose cotransporter inhibition with phlorizin or glucose-free solution greatly reduced Na+ influx in HIP myocytes (to 1.20±0.16 mmol/L per minute), whereas it had no effect in WT cells. Phlorizin also significantly decreased glucose uptake in HIP myocytes (by 33±9%) but not in WT, indicating an increased reliance on the Na+–glucose cotransporter for glucose uptake in T2D hearts.ConclusionsMyocyte Na+–glucose cotransport is enhanced in T2D, which increases Na+ influx and causes Na+ overload. Higher [Na+]i may contribute to arrhythmogenesis and oxidative stress in diabetic hearts.
Long-palped Water Beetles were collected during a taxon expedition in Montenegro which involved citizen scientists, students and taxonomists. The material was collected from springs, brooks, fens and the Tara River, at altitudes between 600 m and 1450 m above sea level, using fine-meshed hand-nets and by manual checking of submerged substrates. The morphological species delimitation was supplemented and congruent with mtDNA sequences mainly obtained in the field using the newly-developed MinION-based ONTrack pipeline. The new species Hydraena dinarica Freitag & de Vries, sp. n. from Durmitor Mt. is described, illustrated and compared in detail to closely-related congeners of the H. saga d'Orchymont, 1930/H. emarginata Rey, 1885 species complex. Five additional species and female specimens of two unidentified morphospecies of the genus were also recorded in the vicinity of Durmitor National Park. New records and the first DNA barcodes for Hydraena biltoni Jäch & Díaz, 2012 (endemic to Montenegro) and H. morio Kiesenwetter, 1849 are provided. Further records of H. nigrita Germar, 1824, H. minutissima Stephens, 1829, H. subintegra Ganglbauer, 1901 and females of two unidentified morphospecies are commented upon. The resulting inter- and intraspecific genetic distances and some observations of low or zero sequence divergence between recently-diverged species of Hydraena Kugelann, 1794 are briefly discussed.
Intracellular Na + concentration ([Na + ] i ) is a key regulator of cardiac Ca 2+ cycling, contractility and metabolism. [Na + ] i is elevated in myocytes from failing hearts, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na + ] i is also increased in type-2 diabetes (T2D) due to enhanced activity of the Na + -glucose cotransporter (SGLT). To test this hypothesis, we used myocardial tissue from humans with T2D and an animal model of late-onset T2D (HIP rats). We found increased SGLT expression in failing hearts from patients with T2D compared to non-diabetic individuals (by 55±16%) and in HIP rat hearts ( vs . age-matched wild-type, WT, littermates; by 59±17%). [Na + ] i , measured with the fluorescent indicator SBFI, is increased in myocytes from diabetic HIP rats, both at rest (14.7±0.9 mM compared to 11.4±0.7 mM in WT) and during electrical stimulation at 2 Hz (17.3±0.8 mM vs . 15.0±0.7 mM in WT). However, the Na + /K + -pump function (measured as the rate of pump-mediated [Na + ] i decline in intact myocytes) is not significantly altered in diabetic HIP rats. This result suggests that higher [Na + ] i is due to an increased Na + entry in HIP rat myocytes. Indeed, Na + influx, assessed as the rate of [Na + ] i rise upon Na + /K + -pump inhibition with 10 mM ouabain, was significantly larger in myocytes from diabetic HIP vs . WT rats (1.74±0.13 mM/min vs . 1.27±0.07 mM/min). SGLT inhibition with 250 μM phlorizin significantly reduced Na + influx in myocytes from diabetic HIP rats (to 1.08±0.20 mM/min), while it had no effect in the WT (1.14±0.21 mM/min). Phlorizin also significantly decreased glucose uptake in HIP rat myocytes (by 50±10 %) but not in WT, indicating an increased reliance on SGLT for glucose uptake in T2D hearts. In agreement with this result, the insulin-sensitive glucose uptake was greatly reduced in HIP rat myocytes vs . WT. These data suggest that SGLT is upregulated in diabetic hearts to compensate for reduced insulin-mediated glucose uptake. In summary, we found that [Na + ] i is elevated in myocytes from diabetic HIP rats due to an increased Na + entry via the Na + -glucose cotransporter. Higher [Na + ] i may contribute to arrhythmogenesis and oxidative stress in diabetic hearts.
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