Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress.

OBJECTIVE: Ribosomal protein S6 Kinase-1 (S6K1) has been linked to resistance exercise-mediated improvements in glycemia. We hypothesized that S6K1 may also play a role in regulating glycemic control in response to endurance exercise training. METHODS: S6k1-knockout (S6K1KO) and WT mice on a 60 cal% high-fat diet were trained for 4 weeks on treadmills, metabolically phenotyped, and compared to sedentary controls. RESULTS: WT mice showed improved glucose tolerance after training. In contrast, S6K1KO mice displayed equally high glucose tolerance already in the sedentary state with no further improvement after training. Similarly, training decreased mitochondrial ROS production in skeletal muscle of WT mice, whereas ROS levels were already low in the sedentary S6K1KO mice with no further decrease after training. Nevertheless, trained S6K1KO mice displayed an increased running capacity compared to trained WT mice, as well as substantially reduced triglyceride contents in liver and skeletal muscle. The improvements in glucose handling and running endurance in S6K1KO mice were associated with markedly increased ketogenesis and a higher respiratory exchange ratio. CONCLUSIONS: In high-fat fed mice, loss of S6K1 mimics endurance exercise training by reducing mitochondrial ROS production and upregulating oxidative utilization of ketone bodies. Pharmacological targeting of S6K1 may improve the outcome of exercise-based interventions in obesity and diabetes.

[Incidence of typical nephrocalcinosis ultrasound findings in premature infants during enteral calcium and phosphate administration]. / Inzidenz nephrokalzinosetypischer Sonographiebefunde bei Frühgeborenen während enteraler Kalzium- und Phosphatgabe.

Supplementation of calcium and phosphate is recommended in nutrition of low birth weight infants to ensure a physiological development of postnatal bone mineralisation. To investigate whether high dose calcium supplementation increases the risk of renal calcification in preterm infants, serial ultrasound examinations were performed in 30 preterm infants (gestational age 29.5 (26-35) weeks; birth weight 1382 (610-2010) g) before, during and after oral calcium and phosphate supplementation. Total calcium input was on average 3.1 mmol/kg/d, total phosphate input on average 2.1 mmol/kg/d). All children showed normal kidney ultrasound before entering the study. During mineral supplementation three children developed hyperechoic renal medullary pyramids, the typical ultrasound pattern of nephrocalcinosis. Supplementation was stopped immediately and pathologic ultrasound patterns disappeared in all 3 children.