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5. The role of glucagon-like peptides in osteosarcopenia.

Author

Tufail, Enaya, Sanyal, Somali, Mithal, Ambrish, Sanyal, Sabyasachi, and Chattopadhyay, Naibedya

Subjects
CYCLIC-AMP-dependent protein kinase, MUSCLE mass, G protein coupled receptors, BONE health, INSULIN sensitivity, GLUCAGON-like peptide-1 receptor
Abstract

Various metabolic abnormalities, including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism and low vitamin D levels, have been linked to both osteopenia and sarcopenia. Osteosarcopenia is also commonly observed in older age groups, notably in postmenopausal women. Glucagon-like peptide-1 (GLP-1), a labile incretin secreted from the intestinal L-cells, stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication. GLP-1 binds to its receptor, the GLP-1 receptor, a G-protein-coupled receptor, and leads to the stimulation of adenylate cyclase, increasing the levels of cyclic AMP (cAMP). Elevated cAMP then activates protein kinase A and other downstream signaling pathways. These signaling cascades result in various cellular responses, such as enhanced insulin secretion from pancreatic beta cells, improved insulin sensitivity and modulation of appetite and gastric emptying. In addition, GLP-1 signaling can promote cell growth and survival, contributing to its effects on muscle and bone health. Its role as an anti-diabetic medication has been enhanced through various modifications to extend its half-life, thereby improving its effectiveness and druggability. GLP-1 analogs, initially developed for diabetes management, have also been harnessed for obesity treatment due to the effect of GLP-1 to induce satiety and slow gastric emptying. Beyond their well-known anti-diabetic and anti-obesity effects, GLP-1 agonists can enhance muscle mass and bone density, making them valuable in addressing conditions such as sarcopenia and osteoporosis. This review focuses on the effects of GLP-1 analogs on musculoskeletal health by critically assessing the underlying signaling mechanisms in order to understand their translational potential for the treatment of osteosarcopenia. [ABSTRACT FROM AUTHOR]

Published
2025
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6. Estradiol overcomes adiponectin-resistance in diabetic mice by regulating skeletal muscle adiponectin receptor 1 expression

Author

Chattopadhyay, Sourav, Joharapurkar, Amit, Das, Nabanita, Khatoon, Shamima, Kushwaha, Sapana, Gurjar, Anagha Ashok, Singh, Abhishek Kumar, Shree, Sonal, Ahmed, Md Zohaib, China, Shyamsundar Pal, Pal, Subhashis, Kumar, Harish, Ramachandran, Ravishankar, Patel, Vishal, Trivedi, Arun Kumar, Lahiri, Amit, Jain, Mukul Rameshchandra, Chattopadhyay, Naibedya, and Sanyal, Sabyasachi

Published
2022
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7. Adiponectin receptors by increasing mitochondrial biogenesis and respiration promote osteoblast differentiation: Discovery of isovitexin as a new class of small molecule adiponectin receptor modulator with potential osteoanabolic function

Author

Pal, Subhashis, Singh, Maninder, Porwal, Konica, Rajak, Sangam, Das, Nabanita, Rajput, Swati, Trivedi, Arun K., Maurya, Rakesh, Sinha, Rohit A., Siddiqi, Mohammad I., Sanyal, Sabyasachi, and Chattopadhyay, Naibedya

Published
2021
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21. Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

Author

Yadav, Manisha, Singh, Abhishek Kumar, Kumar, Harish, Rao, Geeta, Chakravarti, Bandana, Gurjar, Anagha, Dogra, Shalini, Kushwaha, Sapana, Vishwakarma, Achchhe Lal, Yadav, Prem Narayan, Datta, Dipak, Tripathi, Anil Kumar, Chattopadhyay, Naibedya, Trivedi, Arun Kumar, and Sanyal, Sabyasachi

Published
2016
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24. Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

Author

Pal, Subhashis, Khan, Kainat, China, Shyamsundar Pal, Mittal, Monika, porwal, Konica, Shrivastava, Richa, Taneja, Isha, Hossain, Zakir, Mandalapu, Dhanaraju, Gayen, Jiaur R., Wahajuddin, Muhammad, Sharma, Vishnu Lal, Trivedi, Arun K., Sanyal, Sabyasachi, Bhadauria, Smrati, Godbole, Madan M., Gupta, Sushil K., and Chattopadhyay, Naibedya

Published
2016
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25. A butanolic fraction from the standardized stem extract of Cassia occidentalis L delivered by a self-emulsifying drug delivery system protects rats from glucocorticoid-induced osteopenia and muscle atrophy

Author

Pal, Subhashis, Mittapelly, Naresh, Husain, Athar, Kushwaha, Sapana, Chattopadhyay, Sourav, Kumar, Padam, Ramakrishna, Eppalapally, Kumar, Sudhir, Maurya, Rakesh, Sanyal, Sabyasachi, Gayen, Jiaur R., Mishra, Prabhat R., and Chattopadhyay, Naibedya

Published
2020
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30. Ormeloxifene, a nonsteroidal antifertility drug promotes megakaryocyte differentiation in leukemia cell line K562.

Author

Mishra, Mukul, Singh, Anil Kumar, Thacker, Gatha, Upadhyay, Vishal, Sanyal, Sabyasachi, and Trivedi, Arun Kumar

Subjects
RALOXIFENE, CONTRACEPTIVE drugs, CELL differentiation, SELECTIVE estrogen receptor modulators, CELL lines, PHORBOL esters
Abstract

Ormeloxifene (ORM) (3,4‐trans‐2,2‐dimethyl‐3‐phenyl‐4‐p‐(β‐pyrrolidinoethoxy) phenyl‐7‐methoxychroman), world's first nonsteroidal selective estrogen receptor modulator approved for contraception in India has been shown to have potential anticancer activities. Here, we show that ORM can induce megakaryocyte and myeloid (granulocytic) but not erythroid differentiation in multipotent human myeloid leukemia cell line K562. We show that ORM at an IC50 of 7.5 µM can induce morphological changes similar to megakaryocytes in K562 cells. ORM led to increase in levels of megakaryocytic differentiation markers (CD41 and CD61) as well as key transcription factors GATA1 and AML1. We further show that ORM induces megakaryocytic differentiation in K562 cells through ERK activation and induction of autophagy in a fashion similar to other known inducers of megakaryocytic differentiation such as phorbol esters. In addition, as shown earlier, we yet again observed that ORM led to activation of caspases since their inhibition through pan‐caspase inhibitor mitigated megakaryocytic differentiation as they led to significant decrease in CD41 and CD61. Because induction of megakaryocytic differentiation in K562 involves growth arrest and exit from cell cycle, we also observed an increase in levels of p21 and p27 with decrease in c‐Myc protein levels in K562 cells treated with 7.5 µM ORM for 24 and 48 h, respectively. Taken together, these findings indicate that ORM can markedly induce megakaryocytic differentiation in K562 cells. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats: evidence for estrogen receptor β-mediated osteogenic action of medicarpin

Author

Bhargavan, Biju, Singh, Divya, Gautam, Abnish K., Mishra, Jay Sharan, Kumar, Amit, Goel, Atul, Dixit, Manish, Pandey, Rashmi, Manickavasagam, Lakshmi, Dwivedi, Shailendra D., Chakravarti, Bandana, Jain, Girish K., Ramachandran, Ravishankar, Maurya, Rakesh, Trivedi, Arun, Chattopadhyay, Naibedya, and Sanyal, Sabyasachi

Published
2012
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33. Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats

Author

Gautam, Abnish K., Bhargavan, Biju, Tyagi, Abdul M., Srivastava, Kamini, Yadav, Dinesh K., Kumar, Manmeet, Singh, Akanksha, Mishra, Jay S., Singh, Amar Bahadur, Sanyal, Sabyasachi, Maurya, Rakesh, Manickavasagam, Lakshmi, Singh, Sheelendra P., Wahajuddin, Wahajuddin, Jain, Girish K., Chattopadhyay, Naibedya, and Singh, Divya

Published
2011
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36. Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia

Author

Khan, Mohd. Parvez, Singh, Abhishek Kumar, Joharapurkar, Amit Arvind, Yadav, Manisha, Shree, Sonal, Kumar, Harish, Gurjar, Anagha, Mishra, Jay Sharan, Tiwari, Mahesh Chandra, Nagar, Geet Kumar, Kumar, Sudhir, Ramachandran, Ravishankar, Sharan, Anupam, Jain, Mukul Rameshchandra, Trivedi, Arun Kumar, Maurya, Rakesh, Godbole, Madan Madhav, Gayen, Jiaur Rahaman, Sanyal, Sabyasachi, and Chattopadhyay, Naibedya

Published
2015
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39. Orally Active Osteoanabolic Agent GTDF Binds to Adiponectin Receptors, With a Preference for AdipoR1, Induces Adiponectin-Associated Signaling, and Improves Metabolic Health in a Rodent Model of Diabetes

Author

Singh, Abhishek Kumar, Joharapurkar, Amit Arvind, Khan, Mohd. Parvez, Mishra, Jay Sharan, Singh, Nidhi, Yadav, Manisha, Hossain, Zakir, Khan, Kainat, Kumar, Sudhir, Dhanesha, Nirav Anilkumar, Mishra, Devendra Pratap, Maurya, Rakesh, Sharma, Sharad, Jain, Mukul Rameshchandra, Trivedi, Arun Kumar, Godbole, Madan Madhav, Gayen, Jiaur Rahaman, Chattopadhyay, Naibedya, and Sanyal, Sabyasachi

Published
2014
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45. Bile Acid Receptor Agonist GW4064 Regulates PPARγ Coactivator-1α Expression Through Estrogen Receptor-Related Receptor α

Author

Dwivedi, Shailendra Kumar Dhar, Singh, Nidhi, Kumari, Rashmi, Mishra, Jay Sharan, Tripathi, Sarita, Banerjee, Priyam, Shah, Priyanka, Kukshal, Vandana, Tyagi, Abdul Malik, Gaikwad, Anil Nilkanth, Chaturvedi, Rajnish Kumar, Mishra, Durga Prasad, Trivedi, Arun Kumar, Sanyal, Somali, Chattopadhyay, Naibedya, Ramachandran, Ravishankar, Siddiqi, Mohammad Imran, Bandyopadhyay, Arun, Arora, Ashish, Lundåsen, Thomas, Anakk, Sayee Priyadarshini, Moore, David D., and Sanyal, Sabyasachi

Published
2011

47. Single-Cell Proteomics and Tumor RNAseq Identify Novel Pathways Associated With Clofazimine Sensitivity in PI- and IMiD- Resistant Myeloma, and Putative Stem-Like Cells.

Author

Kumar, Harish, Mazumder, Suman, Sharma, Neeraj, Chakravarti, Sayak, Long, Mark D., Meurice, Nathalie, Petit, Joachim, Liu, Song, Chesi, Marta, Sanyal, Sabyasachi, Stewart, A. Keith, Kumar, Shaji, Bergsagel, Leif, Rajkumar, S. Vincent, Baughn, Linda B., Van Ness, Brian G., and Mitra, Amit Kumar

Subjects
MULTIPLE myeloma, CHRONIC myeloid leukemia, RNA sequencing, PROTEOMICS, PROTEASOME inhibitors
Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy with dose-limiting toxicities and inter-individual variation in response/resistance to the standard-of-care/primary drugs, proteasome inhibitors (PIs), and immunomodulatory derivatives (IMiDs). Although newer therapeutic options are potentially highly efficacious, their costs outweigh the effectiveness. Previously, we have established that clofazimine (CLF) activates peroxisome proliferator-activated receptor-γ, synergizes with primary therapies, and targets cancer stem-like cells (CSCs) in drug-resistant chronic myeloid leukemia (CML) patients. In this study, we used a panel of human myeloma cell lines as in vitro model systems representing drug-sensitive, innate/refractory, and clonally-derived acquired/relapsed PI- and cereblon (CRBN)-negative IMiD-resistant myeloma and bone marrow-derived CD138+ primary myeloma cells obtained from patients as ex vivo models to demonstrate that CLF shows significant cytotoxicity against drug-resistant myeloma as single-agent and in combination with PIs and IMiDs. Next, using genome-wide transcriptome analysis (RNA-sequencing), single-cell proteomics (CyTOF; Cytometry by time-of-flight), and ingenuity pathway analysis (IPA), we identified novel pathways associated with CLF efficacy, including induction of ER stress, autophagy, mitochondrial dysfunction, oxidative phosphorylation, enhancement of downstream cascade of p65-NFkB-IRF4-Myc downregulation, and ROS-dependent apoptotic cell death in myeloma. Further, we also showed that CLF is effective in killing rare refractory subclones like side populations that have been referred to as myeloma stem-like cells. Since CLF is an FDA-approved drug and also on WHO's list of safe and effective essential medicines, it has strong potential to be rapidly re-purposed as a safe and cost-effective anti-myeloma drug. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

Author

Gupta, Jyoti, Singh, Dharmendra P., Verma, Prem C., Rahuja, Neha, Srivastava, Rohit, Ahmad, Ishbal, Jaiswal, Natasha, Kumar, Harish, Gupta, Anand P., Gupta, Varsha, Misra, Anamika, Kushwaha, Hari N., Singh, Bhawani, Singh, Sheo K., Dwivedi, Anil K., Gayen, Jiaur R., Sanyal, Sabyasachi, Srivastava, Arvind K., Pratap, Ram, and Tamrakar, Akhilesh K.

Subjects
FRUCTOSE, FARNESOID X receptor, TYPE 2 diabetes, BLOOD sugar, ANIMAL culture, LIVER cells
Abstract

Introduction: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. Methods: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. Results: From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5. Conclusion: Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications. [ABSTRACT FROM AUTHOR]

Published
2022
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