Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Mitigating Diabetes and Gut Dysmotility in Mice: Long-Term Safety and Efficacy of miR-10a/B Treatment with No Indication for Cancer and Inflammation Risks

Rajan Singh
ORCID logo ,
Se Eun Ha
ORCID logo ,
Hahn Sung Park
,
Sushmita Debnath
,
Hayeong Cho
,
Gain Baek
,
Tae Yang Yu
,
Seungil Ro
* ORCID logo
Version 1 : Received: 2 January 2024 / Approved: 3 January 2024 / Online: 3 January 2024 (15:07:06 CET)

A peer-reviewed article of this Preprint also exists.

Singh, R.; Ha, S.E.; Park, H.S.; Debnath, S.; Cho, H.; Baek, G.; Yu, T.Y.; Ro, S. Sustained Effectiveness and Safety of Therapeutic miR-10a/b in Alleviating Diabetes and Gastrointestinal Dysmotility without Inducing Cancer or Inflammation in Murine Liver and Colon. Int. J. Mol. Sci. 2024, 25, 2266. Singh, R.; Ha, S.E.; Park, H.S.; Debnath, S.; Cho, H.; Baek, G.; Yu, T.Y.; Ro, S. Sustained Effectiveness and Safety of Therapeutic miR-10a/b in Alleviating Diabetes and Gastrointestinal Dysmotility without Inducing Cancer or Inflammation in Murine Liver and Colon. Int. J. Mol. Sci. 2024, 25, 2266.

Abstract

Background/Aim: microRNAs (miRNAs) are key regulators of both physiological and pathophysiological mechanisms in diabetes and gastrointestinal (GI) dysmotility. Our previous studies have demonstrated the therapeutic potential of miR-10a-5p mimic and miR-10b-5p mimic (miR-10a/b mimics) in rescuing diabetes and GI dysmotility in murine models of diabetes. In this study, we elucidated the safety profile of a long-term treatment with miR-10a/b mimics in diabetic mice. Methods: Male C57BL6 mice were fed a high-fat, high-sucrose diet (HFHSD) to induce diabetes and treated by five subcutaneous injections of miR-10a/b mimics for a 5-month period. We examined the long-term effect of the miRNA mimics on diabetes and GI dysmotility, including an assessment of cancer risk as well as liver and colon inflammation using cancer and inflammatory biomarkers. Results: HFHSD-induced diabetic mice subcutaneously injected with miR-10a/b mimics monthly for 5 months exhibited a marked reduction in fasting blood glucose levels with restoration of insulin and significant weight loss, improved glucose and insulin intolerance, and restored GI transit time. In addition, the miR-10a/b mimic treated diabetic mice showed no indication of risk for cancer development and inflammation induction in the liver, colon, and blood for the 5 months post injections. Conclusion: This longitudinal study demonstrates that miR-10a/b mimics, when subcutaneously administered in diabetic mice, effectively alleviate diabetes and GI dysmotility for 5 months with no discernible risk for cancer or inflammation in the liver and colon. The sustained efficacy and favorable safety profiles position miR-10a/b mimics as promising candidates in miRNA-based therapeutics for diabetes and GI dysmotility.

Keywords

miR-10a-5p, miR-10b-5p, diabetes, gastrointestinal dysmotility, cancer, inflammation

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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