<b>Glucose load following prolonged fasting increases oxidative stress-linked response in individuals with diabetic complications.</b>

• DOI: 10.2337/figshare.25948636.v1
• Publication Date: 2024-06-21T17:21:28Z
• Authors: Ekaterina von Rau...; Claus Rodemer; Elisabeth Kliemank; Ruben Bulkescher; Marta Campos; Stefan Kopf; Thomas Fleming; Stephan Herzig; Peter P Nawroth; Julia Szendroedi; Johanna Zemva; Alba Sulaj

&lt;p dir="ltr"&gt;&lt;b&gt;Objective: &lt;/b&gt;Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycaemia, can challenge metabolic flexibility antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting T2D.&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Research Design Methods: &lt;/b&gt;Glucose-tolerant individuals (CON, n=10), T2D with (T2D+, n=10) without diabetic complications (T2D-, underwent oral tolerance test before a 5-day fasting-mimicking diet. Peripheral blood mononuclear cells’ (PBMC) resistance ex-vivo dicarbonyl methylglyoxal (MG) exposure was assessed. Markers of detoxification, oxidative stress, mitochondrial biogenesis were analyzed qPCR, complex protein expression assessed western blotting.&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Results: &lt;/b&gt;T2D+ exhibited decreased PBMC against MG, while T2D- remained unchanged, CON improved post-glucose (-19.0% vs. -1.7% 12.6%; all P=0.017). &lt;a href="" target="_blank"&gt;T2D+ showed increased detoxification (mRNA glyoxalase-1, P=0.039), stress glutathione-disulfide-reductase, P=0.006) &lt;/a&gt;&lt;a target="_blank"&gt;and V (all P=0.004) compared &lt;/a&gt;post-glucose fasting. Citrate synthase activity indicating no change number. Mitochondrial HspA9, P=0.032). CON, post-fasting, but not load, mRNA antioxidant defences forkhead-box-O4, P=0.036, glutathione-peroxidase-2, P=0.034), T2D+ (glutathione-peroxidase-2, P=0.04).&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These findings suggest susceptibility glucose-induced might help diet interventions for management.&lt;/p&gt;