Review
Endocrinology & Metabolism
Jacob Bar-Tana
Summary: 'Glucolipotoxicity' and 'insulin resistance' are believed to drive type 2 diabetes and metabolic syndrome, but recent treatments show that alleviating non-glycemic and cardio-renal diseases is possible regardless of glucose lowering and insulin resistance. This opinion article proposes replacing the current paradigm with an 'mammalian target of rapamycin complex 1 (mTORC1) syndrome' (TorS) paradigm, which includes various diseases and may generate novel treatments.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Robert N. Willette, Parth Mangrolia, Stephen M. Pondell, Christopher Young Woo Lee, Sanghee Yoo, Marc S. Rudoltz, Benjamin R. Cowen, Dean J. Welsch
Summary: The study demonstrates that attenuation of fibrogenic metabolic remodeling, by modulation of oxidative phosphorylation with IM156, prevents myofibroblast phenotype/collagen deposition and is a potentially effective and translational antifibrotic strategy.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Review
Medicine, General & Internal
Andreas Zimmermann, Frank Madeo, Abhinav Diwan, Junichi Sadoshima, Simon Sedej, Guido Kroemer, Mahmoud Abdellatif
Summary: Mitochondrial dysfunction and its removal through mitophagy play a central role in ageing and chronic diseases. The regulation of mitophagy involves metabolic pathways and various molecular switches. Understanding the intersection of metabolic regulation and mitophagy can provide insights for delaying ageing and treating mitochondria-associated chronic diseases.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Ziyin Lu, Haozhen Wang, Muhammad Ishfaq, Yufang Han, Xiujin Zhang, Xiang Li, Baoqi Wang, Xiuli Lu, Bing Gao
Summary: This study reveals that quercetin, as an AMPK agonist, can counteract inflammatory damage caused by MG infection, highlighting the potential significance of the AMPK cascade signaling pathway as an important target for anti-inflammatory drug research in avian respiratory diseases.
Article
Chemistry, Medicinal
Yuusuke Tamura, Ippei Morita, Yu Hinata, Eiichi Kojima, Yoshikazu Sasaki, Toshihiro Wada, Mutsumi Asano, Masahiko Fujioka, Yoko Hayasaki-Kajiwara, Takanori Iwasaki, Kenichi Matsumura
Summary: Diabetes is a global healthcare problem and targeting AMPK can be a potential treatment. However, finding direct AMPK activators with high potency for the 132-AMPK isoform and suitable chemical structure is challenging. In this study, we successfully designed a novel activator 14d which showed high in vitro potency, good pharmacokinetic profiles, and dose-dependent blood-glucose-lowering effects in a diabetic animal model. Chronic activation of AMPK with 14d also led to dose-dependent reduction in HbA1c.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Yuusuke Tamura, Ippei Morita, Yu Hinata, Eiichi Kojima, Hiroki Ozasa, Hidaka Ikemoto, Mutsumi Asano, Toshihiro Wada, Yoko Hayasaki-Kajiwara, Takanori Iwasaki, Kenichi Matsumura
Summary: AMP-activated protein kinase (AMPK) plays an important role in exercise-induced metabolic benefits. Activation of AMPK has been explored as a strategy for treating metabolic disorders, such as type 2 diabetes. Existing AMPK activators with different chemical structures have been reported, but direct activators for specific isoforms are limited. The newly designed 4-azaindole derivative 16g showed promising in vitro activity and demonstrated dose-dependent improvements in HbA1c and hepatic lipid accumulation in a diabetic animal model.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Cell Biology
Juliana Portes, Beatriz Bullon, Jose Luis Quiles, Maurizio Battino, Pedro Bullon
Summary: Diabetes and periodontitis are two of the most prevalent diseases worldwide, with inflammation being the main cause. This review aims to emphasize the molecular pathophysiological mechanisms in patients with these two diseases.
Review
Cell Biology
Tapan Behl, Amit Gupta, Aayush Sehgal, Sanchay Sharma, Sukhbir Singh, Neelam Sharma, Camelia Cristina Diaconu, Abbas Rahdar, Abdul Hafeez, Saurabh Bhatia, Ahmed Al-Harrasi, Simona Bungau
Summary: Based on a review of various databases, it has been concluded that activation of AMPK by direct or indirect activators shows great potential in maintaining glucose and lipid metabolism homeostasis, improving insulin sensitivity, and potentially serving as a novel therapy for diabetes and its complications.
INFLAMMATION RESEARCH
(2021)
Article
Integrative & Complementary Medicine
Ruifeng Tian, Jinjie Yang, Xiaoming Wang, Shuaiyang Liu, Ruixiang Dong, Zhenya Wang, Zifeng Yang, Yingping Zhang, Zhiwei Cai, Hailong Yang, Yufeng Hu, Zhi-Gang She, Hongliang Li, Junjie Zhou, Xiao-Jing Zhang
Summary: In this study, a drug repositioning strategy was used to identify potential drug candidates for NAFLD, and honokiol was found to be effective in inhibiting NAFLD progression. Through multiple in vitro and in vivo models, honokiol was shown to improve hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance by activating the AMPK signaling pathway.
Article
Multidisciplinary Sciences
Haekyung Lee, Hyoungnae Kim, Jin Seok Jeon, Hyunjin Noh, Rojin Park, Dong Won Byun, Hye Jeong Kim, Kyoil Suh, Hyeong Kyu Park, Soon Hyo Kwon
Summary: This study evaluated the effects of empagliflozin, an SGLT2 inhibitor, on mitochondrial function and inflammatory environment in the kidneys of type 2 diabetes patients. The results showed that empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response, explaining the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.
SCIENTIFIC REPORTS
(2022)
Review
Endocrinology & Metabolism
Linan Gong, Zanzan Wang, Zhenggui Wang, Zhiguo Zhang
Summary: Sestrin2 is a highly conserved protein that regulates metabolism through pathways like activating AMPK, inhibiting mTOR, etc. Modulation of Sestrin2 activity may provide a potential therapeutic target for preventing metabolic diseases.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lin He, Ruorong Yan, Ziran Yang, Yue Zhang, Xinhua Liu, Jianguo Yang, Xujun Liu, Xiaoping Liu, Lu Xia, Yue Wang, Jiajing Wu, Xiaodi Wu, Lin Shan, Xiaohan Yang, Jing Liang, Yongfeng Shang, Luyang Sun
Summary: The F-box protein JFK promotes lipid accumulation in adipose tissue, leading to the development of metabolic syndrome. Knockout of JFK gene in mice can resist diet-induced metabolic dysfunctions. The interaction between JFK and ING5 disrupts AMPK activity and fatty acid beta-oxidation, suppressing hepatic lipid catabolism and contributing to obesity and metabolic syndrome.
Review
Endocrinology & Metabolism
Filip Jevtovic
Summary: Excess nutrient intake and lack of exercise are common factors in obesity and insulin resistance. Metformin and exercise both target AMPK to improve glucose control but their combined effect is not well supported in literature, with some studies suggesting a possible antagonistic dynamic when these two modalities are combined.
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Alex J. T. Yang, Ahmed Bagit, Rebecca E. K. MacPherson
Summary: Alzheimer's disease is not only associated with protein plaques and amyloid-beta peptides, but also with metabolic dysregulation and diabetes. Resveratrol improves metabolic impairments and cognitive function, but may have adverse effects on synaptic function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Timothy M. E. Davis
Summary: MAFLD is a relatively novel classification that emphasizes the importance of metabolic risk factors in the progression of NAFLD-associated pathology, including in patients with T2D and higher hepatic fat content. This review assesses contemporary methods for quantifying liver fat and fibrosis, with a focus on prognostic implications and interventions for T2D patients. Discussions also include changing epidemiology of obesity and cardiovascular disease, as well as new therapies for MAFLD with potential implications for T2D.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Review
Physiology
Minyu Zhang, Biyang Xiao, Xiaoqi Chen, Bingming Ou, Songtao Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) is closely related to bile acid and gut microbiota disorders. Exercise plays an important role in maintaining the homeostasis of the enterohepatic circulation and the health of the host gut microbiota by regulating the composition and function of the bile acid pool in the enterohepatic axis. Exercise has been recommended as a first-line intervention for NAFLD, and regulating bile acids through exercise may be a promising treatment strategy.
