Drug Mimicking Bariatric Surgery Shows Promise for Type 2 Diabetes Treatment
Researchers have identified a potential drug candidate that replicates the blood sugar-lowering effects of bariatric surgery, offering a new avenue for treating type 2 diabetes. The breakthrough centers on stimulating glucose excretion through the intestines, a phenomenon observed after metabolic surgery.
Understanding Type 2 Diabetes and the Need for New Treatments
Type 2 diabetes, characterized by elevated blood sugar levels due to insufficient insulin production or insulin resistance, is a growing global health concern. While various treatments exist, fundamental cures remain elusive. Bariatric surgery is highly effective for diabetic patients with obesity, but its invasive nature and potential side effects limit its accessibility, with less than 1% of eligible patients undergoing the procedure. This necessitates the development of alternative, less invasive therapies.
The Role of Intestinal Glucose Excretion
Previous research primarily focused on improving insulin sensitivity or reducing intestinal sugar absorption. However, this new study, conducted by researchers at Yonsei University Severance Hospital, investigated ‘glucose excretion through the intestines’ – a process observed following bariatric surgery where glucose is absorbed by intestinal tissue and then expelled via feces. The research team was the first to identify this phenomenon, earning recognition as a top national research achievement in 2022.
Identifying a Key Treatment Target: aPKC·GLUT1 Signaling Axis
The research team analyzed gene expression data from small intestine tissue undergoing bariatric surgery and various models of intestinal glucose excretion. Utilizing an AI-based new drug development platform, they compared over 1 million gene expression datasets to pinpoint factors driving glucose excretion. Their analysis revealed a strong correlation between the activation of protein kinase C (PKC), particularly atypical PKC, and changes in gene expression associated with glucose excretion. Specifically, atypical PKC was found to promote intestinal glucose excretion mediated by GLUT1 (glucose transporter 1).
Promising Results in Diabetic Mouse Models
Activating atypical PKC in intestinal tissue of diabetic mice increased glucose discharge from the blood into the intestinal lumen, resulting in improved blood sugar levels. A candidate substance called ‘Prostatin,’ identified through the AI platform, was shown to activate atypical PKC and enhance this intestinal glucose excretion mechanism.
Implications for Future Diabetes and Weight Loss Treatments
“Through this study, we identified a new treatment target that can maximize intestinal glucose excretion, one of the mechanisms by which blood sugar levels improve after bariatric surgery,” stated Professor Cheol-Ryong Koo of Yonsei University Severance Hospital. “This provides a molecular biological basis for understanding the blood sugar improvement effect of bariatric surgery and suggests the possibility of developing new diabetes and weight loss treatment strategies targeting this signaling pathway.”
Study Details and Funding
This research was supported by the Korea-US Innovation Performance Creation R&D Project, a research-oriented hospital initiative hosted by the Ministry of Health, and Welfare. The findings were published in the international academic journal Nature Communication. Nature Communication