Optimizing intestinal glucotonic effect via atypical protein kinase C

Intestinal glucotonic transformation, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycermic control. This study aims to identify downstream molecules that mediate the function of the identified target as an effective intestinjal glucotonic activator. Altered transcriptomes were evaluated in variable intestinal glucotonic models and big data-based drug discovery systems. Protein kinase C (PKC) activation mimicked transcriptome alterations observed during intestinal glucotonic transformation. Among the PKC subfamilies, atypical PKC (aPKC) promoted glucose transporter 1 (GLUT1)-mediated intestinal glucotonic transformation without inducing oncogenic proliferation. Intestinal aPKC activation via a transposon expression vector induced serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activated aPKC and induced a similar glucotonic effect. Collectively, we identified the prostratin and aPKC/GLUT1 signaling pathways as effective targets for treating diabetes, providing insights into the future development of antidiabetic and weight loss drugs. Overall design: Following RYGB surgery, intestinal tissues from rats were isolated and analyzed using scRNA-seq to investigate the molecular mechanism of aPKC/GLUT1-mediated glucotonic transformation.