The Lower Infusion Rate of Glucose to Maintain Ketogenesis within Normal Level during Surgery

Background: Intraoperative low-dose glucose infusions suppress ketogenesis and attenuate postoperative insulin resistance (IR). However, the appropriate rate for intraoperative glucose infusion remains unclear, although a postoperative infusion of 0.08 g/kg/h effectively suppressed ketogenesis at the next morning. Therefore, we investigated the effects of an intraoperative rate of 0.08 g/kg/h on ketogenesis and postoperative IR. Methods: The present study included 15 patients who were undergoing maxillofacial surgery. The patients received glucose-free Ringer’s solution and a continuous glucose infusion (0.08 g/kg/h) during the surgery. Blood samples were collected to evaluate the concentrations of noradrenaline, cortisol, glucose, insulin, ketone bodies, and free fatty acid before anesthesia induction (T1), at 1 h after induction (T2), at 3 h after induction (T3), and at the end of surgery (T4). The glucose clamp test was performed on the days before and after surgery using the STG-55TM device. IR was quantified using the mean glucose infusion rate (M-value). Results: All 15 patients exhibited intraoperative blood glucose concentrations of 90 - 130 mg/dL. There was a non-significant trend towards higher plasma concentrations of total ketone bodies at T3 (p = 0.058). The plasma concentrations of acetoacetic acid at T3 and T4 were significantly higher than that at T1 (p = 0.0217 and p = 0.0306, respectively). All patients exhibited lower M-values after surgery (mean reduction: 48.0% ± 17.9%). Conclusion: Continuous intraoperative glucose at 0.08 g/kg/h helped maintain blood glucose concentrations, although it may suppress the ketogenesis to increase during surgery.

The anorectic response to growth hormone in obese rats is associated with increased ketogenesis: A short communication

The purpose of this study was to investigate whether obese rats with a strong anorectic response to growth hormone also showed signs of increased hepatic ketogenesis as reflected in circulating β-hydroxybutyrate levels. Rats with diet-induced obesity were allocated to one of two groups, receiving either vehicle (n = 7) or 4 mg/kg/d of growth hormone (n = 13) for 4 days. This latter group was later split into a group of responders (n = 8) showing a cumulated reduction of food intake of more than 4 g from base line during the last two days of administrations and a group of non-responders (n = 5). The cumulated reduction of food intake from baseline among the responders was 10.8 ±1.5 g. The corresponding marginal reductions in the non-responder and vehicle groups were 0.5 ±3.4 gand 0.5 ±3.7 g, respectively. Growth hormone administration generally increased serum levels of β-hydroxybutyrate and free fatty acids, compared with vehicle, whereas triglycerides were decreased. Among the responders this effect was statistically significant in all instances whereas the same trend was weaker among non-responders. The main finding of the present study was that the serum β-hydroxybutyrate levels of 0.76 ± 0.11 mmol/l among responders was three times higher than non-responders

Effects of Ranolazine on Carbohydrate Metabolism in the Isolated Perfused Rat Liver

The action mechanism of ranolazine, an antiangina drug, could be at least partly metabolic, including inhibition of fatty acid oxidation and stimulation of glucose utilization in the heart. The purpose of the present work was to investigate if ranolazine affects hepatic carbohydrate metabolism. For this purpose, the hemoglobin-free isolated perfused rat liver was used as the experimental system. Ranolazine increased glycolysis and glycogenolysis and decreased gluconeogenesis. These effects were accompanied by an inhibition of oxygen consumption. The drug also changed the redox state of the NAD+-NADH couple. For the cytosol, increased NADH/NAD+ ratios were observed both under glycolytic conditions as well as under gluconeogenic conditions. For the mitochondria, increased NADH/NAD+ ratios were found in the present work in the absence of exogenous fatty acids in contrast with the previous observation of a decreasing effect when the liver was actively oxidizing exogenous oleate. It seems likely that ranolazine inhibits gluconeogenesis and increases glycolysis in consequence of its inhibitory actions on energy metabolism and fatty acid oxidation and by deviating reducing equivalents in favour of its own biotransformation. This is in line with the earlier postulates that ranolazine diminishes fatty acid oxidation, shifting the energy source from fatty acids to glucose.

Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation

Ketone bodies have beneficial metabolic activities,and the induction of plasma ketone bodies is a health promotion strategy.Dietary supplementation of sodium butyrate(SB)is an effective approach in the induction of plasma ketone bodies.However,the cellular and molecular mechanisms are unknown.In this study,SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2),a rate-limiting enzyme in ketogenesis,to promote ketone body production in hepatocytes.SB administrated by gavage or intraperitoneal injection significantly induced bloodβ-hydroxybutyrate(BHB)in mice.BHB production was induced in the primary hepatocytes by SB.Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis.However,the alteration was mostly observed in mitochondrial proteins with 41%down-and 65%up-regulation,respectively.Succinylation status of HMGCS2 protein was altered by a reduction at two sites(K221 and K358)without a change in the protein level.The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice.The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver.The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis.The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.