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Animal Models of Genetic Obesity: Peripheral Tissue Changes
Published in Claude Bouchard, The Genetics of Obesity, 2020
Patricia R. Johnson, Francine Gregoire
To date, none of the studies of gene products that have been considered as potential candidates for one of the obese mutant genes in rodent models have led to direct identification of the primary lesion(s) produced by the mutant gene. To date, none of the mutant genes have been cloned and sequenced; thus, their protein products remain unknown. The fact that there are so many specific abnormalities of metabolic regulation and gene expression occurring in obese rodent models has led our laboratory to propose that the lesion(s) produced by obese mutant genes is likely to be a regulatory defect that is subsequently expressed in various ways in different tissues — i.e., a pleotropic effect. Further studies designed to look at regulatory pathways in early stages of development of obesity appear to be a fruitful approach, as well as continued efforts to clone and sequence the mutant genes.
Attributes of Peripheral Dopamine and Dopamine Receptors
Published in Nira Ben-Jonathan, Dopamine, 2020
Efficient conversion of food into energy and basic nutrients is contingent upon having a coordinated cooperation between a duct system that transports the food and accessory organs and glands that facilitate food processing. The primary organs that regulate metabolism include the brain (primarily the hypothalamus), endocrine pancreas, liver, and adipose tissue, with important contributions to metabolic regulation coming from the thyroids, pituitary, adrenals, kidneys, and skeletal muscle (Figure 6.8).
Insulin Receptors in the Nucleus of the Solitary Tract and Related Neuronal Circuits
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
The results of numerous studies have demonstrated that the nucleus of the solitary tract (NTS) is involved in the regulation of complex autonomic functions. Located in the dorsal medulla oblongata, the NTS extends between the facial nucleus and the decussation of the pyramidal tract. At the level of the obex, the bilateral medial parts merge to the subcommissural nucleus of the NTS. A number of neurochemical substances, including classical neurotransmitters, neuropeptides, and their receptors, i.e., catecholamines, substance P, neuropeptide Y, etc., have been demonstrated within its various subnuclei,1-3 indicating a highly differentiated neuronal interaction and integration of information from intrinsic and extrinsic sources. The NTS plays an important physiologic role for various autonomic functions, i.e., cardiovascular and respiratory regulation, and involvement in olfaction and taste. Among these important functional activities, our present paper will focus on the significance of the NTS in metabolic regulation via hormones and hormone receptors, in particular, receptors for insulin and the related insulin-gene family, i.e., insulin-like growth factor I (IGF-I).
Chinese herbal compound Huangqin Qingrechubi capsule reduces lipid metabolism disorder and inflammatory response in gouty arthritis via the LncRNA H19/APN/PI3K/AKT cascade
Published in Pharmaceutical Biology, 2023
Xianheng Zhang, Jian Liu, Yanqiu Sun, Qin Zhou, Xiang Ding, Xiaolu Chen
Adipokines are adipose tissue-derived factors that act on distant target organs through blood circulation, participating in metabolic regulation. Adiponectin (APN) is one such factor secreted in large quantities in human plasma. APN can increase insulin sensitivity and enhance the hypoglycemic effect, representing a potential target for diabetes and atherosclerosis (Lei et al. 2021; Nielsen et al. 2021). With the deepening of research, the role of APN in inflammation is gradually recognized. APN can play an anti-inflammatory or pro-inflammatory role in different diseases (Choi et al. 2020). Since GA is an inflammatory disease accompanied by abnormal lipid metabolism, it is particularly necessary to explore the role of APN in the process of GA, but currently, there is a lack of relevant research.
Screening and characterisation of a novel efficient tumour cell-targeting peptide derived from insulin-like growth factor binding proteins
Published in Journal of Drug Targeting, 2023
Min-Lin He, Jin Lei, Xue-Wei Cao, Jian Zhao, Fu-Jun Wang
Insulin-like growth factor (IGF) is a natural growth hormone that plays a key role in cell proliferation, early development, metabolic regulation and inhibition of apoptosis [5]. IGFs are ubiquitously expressed and are important mitogens that affect cell growth and metabolism [6]. The IGF family consists of insulin and two insulin-like factors (IGF-1 and IGF-2). These factors directly regulate cellular function by interacting with specific IGF receptors and activating various intracellular signalling cascades. Numerous mutations in the IGF-1R gene and growth hormone-insulin-like growth factor (GH-IGF) axis genes have been detected in some tumours such as breast cancer, gastrointestinal stromal tumour, and osteosarcoma [7]. These findings have drawn increasing attention to the relationship between the IGF family regulation and tumorigenesis. Under normal physiological conditions, IGF signalling is tightly controlled at a stable level [8]. However, genetic abnormalities and/or chromosomal alterations can lead to disordered expression of IGF and IGF-1R and tumorigenesis [9]. Numerous experiments have shown that an increase in the concentration of IGF-1 leads to the proliferation of tumour cells [10].
Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Amany Belal, Nagwa M. Abdel Gawad, Ahmed B. M. Mehany, Mohammed A. S. Abourehab, Hazem Elkady, Ahmed A. Al‐Karmalawy, Ahmed S. Ismael
It is worth mentioning that, dual-specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3) is a regulator of phase transition during mitosis32. Furthermore, it is able to promote mTORC1 activity, which is associated with resistance to EGFR-mediated endocrine therapy, and other forms of targeted therapy, also it regulates fundamental cellular functions including transcription, translation, proliferation, growth and survival33. Moreover, Glycogen synthase kinase 3 (GSK3) is involved in modulating numerous signalling pathways affecting metabolism, tumorigenesis, proliferation, apoptosis, autophagy, development, and differentiation involved in metabolic regulation34. GSK3 inhibitors were reported to suppress breast tumour growth in pre-clinical models35,36.