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Review
. 2021 Sep;70(9):939-957.
doi: 10.1007/s00011-021-01488-5. Epub 2021 Jul 28.

A spotlight on underlying the mechanism of AMPK in diabetes complications

Tapan Behl  1 , Amit Gupta  2 , Aayush Sehgal  2 , Sanchay Sharma  2 , Sukhbir Singh  2 , Neelam Sharma  2 , Camelia Cristina Diaconu  3   4 , Abbas Rahdar  5 , Abdul Hafeez  6 , Saurabh Bhatia  7   8 , Ahmed Al-Harrasi  8 , Simona Bungau  9
Affiliations
Review

A spotlight on underlying the mechanism of AMPK in diabetes complications

Tapan Behl et al. Inflamm Res. 2021 Sep.

Abstract

Objective: Type 2 diabetes (T2D) is one of the centenarian metabolic disorders and is considered as a stellar and leading health issue worldwide. According to the International Diabetes Federation (IDF) Diabetes Atlas and National Diabetes Statistics, the number of diabetic patients will increase at an exponential rate from 463 to 700 million by the year 2045. Thus, there is a great need for therapies targeting functions that can help in maintaining the homeostasis of glucose levels and improving insulin sensitivity. 5' adenosine monophosphate-activated protein kinase (AMPK) activation, by various direct and indirect factors, might help to overcome the hurdles (like insulin resistance) associated with the conventional approach.

Materials and results: A thorough review and analysis was conducted using various database including MEDLINE and EMBASE databases, with Google scholar using various keywords. This extensive review concluded that various drugs (plant-based, synthetic indirect/direct activators) are available, showing tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without causing insulin resistance, and improving insulin sensitivity. Moreover, these drugs have an effect against diabetes and are therapeutically beneficial in the treatment of diabetes-associated complications (neuropathy and nephropathy) via mechanism involving inhibition of nuclear translocation of SMAD4 (SMAD family member) expression and association with peripheral nociceptive neurons mediated by AMPK.

Conclusion: From the available information, it may be concluded that various indirect/direct activators show tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without resulting in insulin resistance, and may improve insulin sensitivity, as well. Therefore, in a nut shell, it may be concluded that the regulation of APMK functions by various direct/indirect activators may bring promising results. These activators may emerge as a novel therapy in diabetes and its associated complications.

Keywords: AMPK activity; Direct AMPK regulators; Indirect AMPK regulators; Type 2 diabetes.

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References

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    1. Gupta A, Behl T, Sehgal A, Bhatia S, Jaglan D, Bungau S. Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy. Mol Biol Rep. 2021;22:1–4.
    1. CDC. U.S. Department of Health and Human Service. Center for Disease Control and Prevention. National Diabetes Statistics Report, 2020. https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html ; https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-stat... . Accessed 28 Jul
    1. Gupta A, Behl T, Sehgal A, Bhardwaj S, Singh S, Sharma N, Hafeez A. Exploring the recent molecular targets for diabetes and associated complications. Mol Biol Rep. 2021;24:1–7.
    1. Gupta A, Behl T, Panichayupakaranan P. A review of phytochemistry and pharmacology profile of Juglans regia. Obes Med. 2019;16: 100142. https://doi.org/10.1016/j.obmed.2019.100142 . - DOI

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