Hyperbaric oxygen therapy reduces renal lactate production.

Intrarenal hypoxia is an acknowledged factor contributing to the development of diabetic nephropathy. Hyperbaric oxygen (HBO) therapy is a well-known adjuvant treatment for several medical conditions, such as decompression sickness, infections, and wound healing. The underlying metabolic response of HBO is largely unknown. In this study, we investigated the effect of HBO on the intrarenal metabolic alteration in diabetes. Hyperpolarized [1-13C]pyruvate MRI was performed to assess intrarenal energy metabolism in normoglycemic controls and short-term (2 weeks) streptozotocin-induced diabetic rats with and without HBO for five consecutive days. HBO therapy blunted intrarenal lactate production, 3 days after the therapy, in both normoglycemic controls and diabetic rats without affecting either lactate dehydrogenase mRNA expression or activity. HBO therapy reduced lactate formation in both normoglycemic and hyperglycemic rats. These findings support hyperpolarized [1-13C]pyruvate MRI as a novel method for monitoring HBO therapy via the pyruvate to lactate conversion.

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized 13 C,15 N-Urea.

PURPOSE: In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient. METHODS: Hyperpolarized three-dimensional balanced steady state 13 C MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group. RESULTS: A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription. CONCLUSION: MRI and hyperpolarized [13 C,15 N]urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77:1650-1655, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Early diabetic kidney maintains the corticomedullary urea and sodium gradient.

Early diabetic nephropathy is largely undetectable before substantial functional changes have occurred. In the present study, we investigated the distribution of electrolytes and urea in the early diabetic kidney in order to explore whether pathophysiological and metabolic changes appear concomitantly with a decreased sodium and urea gradient. By using hyperpolarized (13)C urea it was possible to measure the essential intrarenal electrolyte gradients and the acute changes following furosemide treatment. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney.

Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate.

In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1-(13)C]acetate magnetic resonance spectroscopy, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin (STZ)-induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type-1 diabetes model.