Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 2 Articles
Opioid receptors represent a crucial class of G-protein coupled receptors [GPCRs] that mediate both the therapeutic and adverse effects of opioids. Since the mid-20th century, research has characterized the major opioid receptor subtypes μ, ẟ, κ and NOP each with distinct endogenous ligands, distribution and roles in analgesia, mood regulation and homeostatic functions. While opioids remain indispensable in clinical pain management, their chronic use is associated with tolerance, physical dependence and addiction. Molecular studies reveal that acute opioid receptor activation suppresses adenylyl cyclase activity, reduces intracellular cAMP, inhibits pre-synaptic calcium ions influx and promotes post synaptic potassium ions efflux, leading to analgesia via neuronal hyperpolarization. However, chronic exposure upregulates the cAMP/PKA pathway, enhances CREB mediated transcription and activates β-arrestin signalling, driving long term neuroadaptations, receptor desensitization and withdrawal syndromes. Importantly, physical dependence reflects adaptive homeostatic changes requiring continuous drug presence, whereas addiction is characterized by compulsive use, dysregulate dopamine signalling and enduring behavioural and psychological changes. These insights not only highlight the complexity of opioid receptor pharmacology but also provide the foundation for developing safer analgesics and therapeutic strategies to dependence and addiction....
NAFLD has emerged as a global burden as 60 and 86% of diabetic patients are diagnosed with insulin resistance induced NAFLD. NAFLD is characterised by unwanted triglyceride agglomeration in the liver tissues due to excess influx of free fatty acids from dysfunctional and insulin resistant adipose tissues and de novo lipogenesis in liver tissues. NAFLD as well as the development of cirrhosis, steatohepatitis and hepatocellular carcinoma are more prevalent in subjects suffering from DM, specifically type 2; are corelated with insulin resistance. This review has primarily focused on establishment of the mechanism of crosstalk between NAFLD and associated metabolic disorders specifically insulin resistance. DNL, a highly regulated process, which upon dysregulation may lead to various metabolic disorders including DM, obesity and NAFLD. NAFLD patients demonstrated significantly higher DNL in their hepatic tissues, while impairment of phosphorylation of AKT, GSK3β and IRK, reduced hepatic insulin signalling. Furthermore, progression of NAFLD that are associated with insulin resistance and other metabolic syndromes is reported to involve multiple signaling pathways and mechanisms. Modulation in the levels of several protein kinases which are involved in signaling pathway may lead to insulin resistance. Similarly, oxidative stress, endoplasmic reticulum stress and mitochondrial dysfunction may also develop insulin resistance NAFLD. Here, this review has summarized various pathophysiology and signaling mechanisms of NAFLD associated to insulin resistance and crosslink between NAFLD and metabolic disorders such as insulin resistance. Such findings can further lead to development of novel therapeutic strategies for NAFLD associated to insulin resistance....
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