Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus
Year: 2026
Type: article
Abstract: Intestinal glucose excretion, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycaemic control. Here, we investigate molecular mechanisms that activate intestinal glucose excretion. We evaluate altered transcriptomes in variable intestinal glucose excretion models and big data-based drug discovery systems. We show that protein kinase C (PKC) activation mimics transcriptome alterations observed during intestinal glucose excretion. Among PKC subfamilies, atypical PKC (aPKC) facilitates glucose transporter 1 (GLUT1)-mediated intestinal glucose excretion without inducing oncogenic proliferation. Intestinal aPKC activation via transposon expression vector induces serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activates aPKC and induces a similar effect on intestinal glucose excretion. We identify the prostratin and aPKC/GLUT1 signalling pathways as putative targets for treating diabetes, providing insights into the future development of antidiabetic and weight-loss drugs. Intestinal glucose excretion is a gut-based mechanism contributing to improved glycemic control after weight-loss surgery. Here, the authors describe a signaling pathway that drives intestinal glucose uptake and luminal excretion, identifying a potential therapeutic target for diabetes and weight loss.
Source: Nature Communications
Authors: Chan Woo Kang, Zhen-Yu Hong, Ju Hun Oh, Mohamed El-Agamy Farh, Eun Kyung Wang, Soohyun Lee, Un Ho Kang, Jung Ho Nam, Yang Jong Lee, Hyeju Shin, Ye Bin Kim, Hyeonuk Jeon, Jae Woong Jeong, Doyeon Kim, Jung Seung Kim, Seung Soo Hong, Jong-Pil Park, Hyo Je Cho, Sungsoon Fang, Hyongbum Henry Kim, Arthur Cho, Byung Kook Lim, Insuk Sohn, Cheol Ryong Ku
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Award: G6380830294
OpenAlex ID: W7127937501