Mimicking gastric bypass glucotonic effect: the role of atypical PKC activation and GLUT1

Bariatric surgery has demonstrated a significant therapeutic impact in reducing obesity and achieving euglycemia in diabetic patientspatients with diabetes. We previously demonstrated that iIntestinal glucotonic transformation, defined as increased intestinal serum glucose uptake and secretion into the lumen, has anplays a vital important role in bypass surgeryies. Altered transcriptomes were evaluated in variable intestinal glucotonic models and big-data artificial intelligence AI-based drug discovery systems. We found noted that protein kinase C (PKC) activation mimics the intestinal transcriptome changes alterations observed in during intestinal glucotonic transformation. Among PKC subfamilies, atypical PKC promotes GLUT1- mediated intestinal glucotonic transformation without inducing oncogenic proliferation. Intestinal aPKC activation through via the transposon expression vector induces serum glucose uptake into intestinal tissue and excretion into the lumeinal space. . Prostratin, a non-tumorigenic phorbol ester, was found observed to activate aPKC and induce a similar glucotonic effect. Taken together, our study results highlightCollectively, we identified a a new chemical compound and target molecular pathways that may provide a distinct and effective approach to to treating diabetes . Overall design: DEG collection from five pairwise comparisons; Transcriptome data from five different pairwise comparisons of glucotonic and non-glucotonic tissue/cells were applied to screen for potential drugs/targets through REMEDY platform. Three comparisons are from RYGB operated glucotonic tissue and sham operated non-glucotonic tissue. These are pair one: RYGB alimentary limb (AL) vs. Sham, jejunum part (Sham JEJU), pair two: RYGB common limb (CL) vs. Sham, ileum part (Sham IL), and pair three: RYGB distal intestine from Otsuka Long-Evans Tokushima Fatty (OLETF) rat (OLE-RYGB CL) vs. sham distal intestine from OLETF rat (OLE-Sham IL). Another comparison involves the glucotonic and non-glucotonic sections of the intestine in rats that underwent RYGB, indicated as pair four: RYGB CL+ vs. RYGB CL-. The last one is from heparin-binding epidermal growth factor-like growth factor (HB-EGF) treated and non-treated (NT) cells, indicated as pair five: intestine epithelial cell line (IEC18)-HBEGF vs. IEC18-NT.