Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus
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.
Authors
- Jung Seung Kim
- Jung Ho Nam (ORCID: https://orcid.org/0009-0007-5001-5875)
- Insuk Sohn (ORCID: https://orcid.org/0000-0003-2126-9378)
- Jae Woong Jeong (ORCID: https://orcid.org/0000-0003-4740-3467)
- Chan Woo Kang (ORCID: https://orcid.org/0000-0001-5822-5235)
- Mohamed El-Agamy Farh (ORCID: https://orcid.org/0000-0003-1696-5934)
- Ju Hun Oh (ORCID: https://orcid.org/0000-0003-0795-6649)
- Arthur Eung-Hyuck Cho (ORCID: https://orcid.org/0000-0001-8670-2473)
- Sungsoon Fang (ORCID: https://orcid.org/0000-0003-0201-5567)
- Ye Bin Kim (ORCID: https://orcid.org/0009-0006-4296-845X)
- Yang Jong Lee (ORCID: https://orcid.org/0000-0002-4620-5621)
- Hyeonuk Jeon
- Soohyun Lee
- Hyeju Shin
- Byung Kook Lim
- Hyo Je Cho
- Doyeon Kim
- Jong-Pil Park
- Cheol Ryong Ku
- Un Ho Kang
- Zhen-Yu Hong
- Seung Soo Hong
Institutions
- Soongsil University (KR)
- Chungbuk National University (KR)
- Yonsei University (KR)
- Nexen (Canada) (CA)
- University of California San Diego (US)
- Gangnam Severance Hospital (KR)
- Yonsei University Health System (KR)
- Frontier Aerospace Corporation (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-06
- DOI
- https://doi.org/10.1038/s41467-026-69193-7
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Korea Health Industry Development Institute
- Ministry of Science and ICT, South Korea