Biology subjects

Birkenfeld, A. L.

Publications and source records attributed to Birkenfeld, A. L..

3 recordsLinked to original sources

bioRxiv2024

Influence of insulin sensitivity on food cue evoked functional brain connectivity in children

ObjectiveInsulin resistance during childhood is a risk factor for developing type 2 diabetes and other health problems later in life. Studies in adults have shown that insulin resistance affects regional and network activity in the brain which are vital for behavior, e.g. ingestion and metabolic control. To date, no study has investigated whether brain responses to food cues in children are associated with peripheral insulin sensitivity. MethodsWe included 53 children (36 girls) between the age of 7-11 years, who underwent an oral Glucose Tolerance Test (oGTT) to estimate peripheral insulin sensitivity (ISI). Brain responses were measured using functional magnetic resonance imaging (fMRI) before and after glucose ingestion. We compared food-cue task-based activity and functional connectivity (FC) between children with low and high ISI, adjusted for age and BMIz. ResultsIndependent of prandial state (i.e., glucose ingestion), children with lower ISI showed higher FC between the anterior insula and caudate and lower FC between the posterior insula and mid temporal cortex than children with higher ISI. Sex differences were found based on prandial state and peripheral insulin sensitivity in the insular FC. No differences were found on whole-brain food-cue reactivity. ConclusionsChildren with low peripheral insulin sensitivity showed differences in food cue evoked response particularly in insula functional connectivity. These differences might influence eating behavior and future risk of developing diabetes.

neuroscience↗

bioRxiv2023

mitoBKCa is functionally expressed in murine and human breast cancer cells and promotes metabolic reprogramming

Alterations in the function of K+ channels such as the voltage- and Ca2+ activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with cell permeable BKCa channel blocker, we show that mitoBKCa modulates overall cellular and mitochondrial energy production and mediates the metabolic rewiring referred to as the "Warburg effect", thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCa and BKCa transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCa could represent a treatment strategy for selected BC patients in future.

cancer biology↗

bioRxiv2023

Engineering of human myotubes toward a mature metabolic and contractile phenotype

1.Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations. We monitored the differentiation process starting from primary human CD56-positive myoblasts in the presence/absence of IGF1 in serum-free medium in daily collected samples for 10 days. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon electrical pulse stimulation following day 6. Myotubes without IGF1 were almost incapable of contraction. IGF1-treatment shifted the proteome toward skeletal muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7 and reduced MYH1/2 suggest a more oxidative phenotype further demonstrated by higher abundance of proteins of the respiratory chain and elevated mitochondrial respiration. IGF1-treatment also upregulated GLUT4 and increased insulin-dependent glucose uptake compared to myotubes differentiated without IGF1. To conclude, utilizing IGF1, we engineered human myotubes that recapitulate the physiological traits of skeletal muscle in vivo superior to established protocols and overcome limitations of previous standards. This novel "easy to use" model enables investigation of exercise on a molecular level. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=85 SRC="FIGDIR/small/544344v3_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@be17b5org.highwire.dtl.DTLVardef@6a2d2org.highwire.dtl.DTLVardef@1abbd52org.highwire.dtl.DTLVardef@1a721f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗