Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage

Here are the Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage journals presenting the latest research across various disciplines. From social sciences to technology, each article is expected to provide valuable insights to our readers.

Glp 1 inhibitor oral, glp 1 agonist benefits, glp 1 for obesity, glp 1 agonist in patients, glp 1 small bowel obstruction, glp 1 agonist for obesity, intestinal nodes.

Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage

Glucagon-like peptide 1 (GLP1), which is mainly processed and cleaved from proglucagon in enteroendocrine cells (EECs) of the intestinal tract, acts on the GLP1 receptor in pancreatic cells to stimulate insulin secretion and to inhibit glucagon secretion. However, GLP1 processing is not fully understood. Here, we show that reticulon 4B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, interacts with the major proglucagon fragment of proglucagon to retain proglucagon on the ER, thereby inhibiting PCSK1-mediated cleavage of proglucagon in the Golgi. Intestinal Nogo-B knockout in male type 2 diabetes mellitus (T2DM) mice increases GLP1 and insulin levels and decreases glucagon levels, thereby alleviating pancreatic injury and insulin resistance. Finally, we identify aberrantly elevated Nogo-B expression and inhibited proglucagon cleavage in EECs from diabetic patients. Our study reveals the subcellular regulatory processes involving Nogo-B during GLP1 production and sugg ests intestinal Nogo-B as a potential therapeutic target for T2DM. © The Author(s) 2024.

Authors : Gong K.; Xue C.; Feng Z.; Pan R.; Wang M.; Chen S.; Chen Y.; Guan Y.; Dai L.; Zhang S.; Jiang L.; Li L.; Wang B.; Yin Z.; Ma L.; Iwakiri Y.; Tang J.; Liao C.; Chen H.; Duan Y.

Source : Nature Research