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Molecular Mechanisms of Brain Insulin Signaling 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Simran Chopra, Robert Hauffe, André Kleinridders
The insulin signaling pathway is a tightly regulated molecular mechanism that controls a range of metabolically important functions in cells and generally induces energy-consuming processes, such as protein synthesis, growth, and proliferation. Moreover, it also controls both peripheral metabolic functions (e.g., glucose uptake or hepatic glucose production), as well as central metabolic functions (e.g., control of appetite and thus food intake). As such, a hyperactivation could lead to detrimental metabolic outcomes. To counteract the hyperactivation of the insulin response, the signaling pathway is subjected to a variety of negative feedback modulations on most of its protein components via posttranslational modifications, transcriptional control, and targeted protein degradation. However, if these feedback loops are continually activated, a chronic insulin-resistant state can occur.
Neurodegeneration in Diabetes Mellitus
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Narsingh Verma, Smriti Rastogi
In general, diabetes mellitus induces stress in neurons through the following mechanisms: disruption of glucose metabolism, andimpairment of the insulin signaling pathway.
Insulin Resistance
Published in Jack L. Leahy, Nathaniel G. Clark, William T. Cefalu, Medical Management of Diabetes Mellitus, 2000
With the foregoing overview of normal insulin action, one can now appreciate that defects in any one of the multiple steps of the insulin-signaling cascade can induce an insulin-resistant state. Alterations in insulin production, insulin binding, or intracellular signaling, all have the potential to induce an insulin-resistant state. For example, a mutation in the gene coding for the insulin molecule can give rise to an abnormal beta-cell product, which is associated with a decreased biological effect. These clinical conditions have been referred to as mutant insulin syndromes, whereby single amino acid substitutions in regions of the molecule that interact with the insulin receptor with reduced affinity ultimately result in an impaired biological action. An example of an acquired defect associated with insulin resistance is anti-insulin antibodies. In this state, antibodies directed against the insulin molecule can complex with insulin and reduce the amount available to target insulin receptors. Fortunately, high titers of insulin antibodies are now rare owing to the common use of recombinant human insulin. Such examples as just cited are referred to as prereceptor causes of insulin resistance, for these defects occur before or at the binding of insulin to the receptor. The insulin resistance most commonly observed clinically is referred to as apostrecep- tor defect because insulin signaling or effective glucose transport after insulin binding (e.g., intracellular events) is attenuated.
Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
Published in Pharmaceutical Biology, 2023
Vivian Soetikno, Prisma Andini, Miskiyah Iskandar, Clark Christensen Matheos, Joshua Alward Herdiman, Iqbal Kevin Kyle, Muhammad Nur Imaduddin Suma, Melva Louisa, Ari Estuningtyas
Next, we evaluated the insulin signalling pathway and its relationship to AMPK. A previous study has shown that insulin signalling and AMPK show vital roles in balancing intracellular energy levels and glucose uptake, in which both pathways stimulate energy conservation and survival of muscle exposed to severe glucose deprivation (Chopra et al. 2012). It has been demonstrated that insulin signaling is mediated by IRS protein. IRS1 is the most common and widely expressed in many tissues including the liver. Metabolic effects of insulin downstream of IRS proteins are mediated by the PI3K (Gallagher et al. 2012). In the present study, HF/HG/STZ administration was able to downregulate the level of IRS1 and PI3K as compared to that of normal rats, while the administration of α-MG at both doses and metformin showed an increase in IRS1 and PI3K. This result is consistent with evidence that α-MG activates insulin signalling and protects pancreatic β-cells against STZ-induced apoptotic damage (Lee et al. 2018).
Association between the Extent of Peripheral Blood DNA Methylation of HIF3A and Accumulation of Adiposity in community-dwelling Women: The Yakumo Study
Published in Endocrine Research, 2022
Genki Mizuno, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Ryosuke Fujii, Yoshiki Tsuboi, Atsushi Teshigawara, Itsuki Kageyama, Keisuke Osakabe, Keiko Sugimoto, Hiroaki Ishikawa, Naohiro Ichino, Yoshiji Ohta, Koji Ohashi, Shuji Hashimoto, Koji Suzuki
Obesity is a major public health concern worldwide. Non-esterified fatty acids, adipokines, and other factors are extensively released from adipose tissues in obese individuals, thereby leading to abnormalities in obesity-related cell functions.1 These substances cause alterations that dysregulate insulin signaling molecules such as insulin receptor substrate, resulting in insulin resistance in the liver and skeletal muscle. Consequently, obesity induces various diseases, such as insulin resistance, type 2 diabetes, and cardiovascular disease.2,3 Thus, obesity is a risk factor for various metabolic diseases, and preventing obesity helps to prevent metabolic diseases. Recent changes in lifestyles and food choice patterns (such as lack of exercise and nontraditional diets) have increased the number of obese individuals globally.4 Lifestyle, environmental, and genetic factors trigger obesity.5,6
The effect of tramadol on blood glucose concentrations: a systematic review
Published in Expert Review of Clinical Pharmacology, 2020
Samaneh Nakhaee, Jeffrey Brent, Christopher Hoyte, Khadijeh Farrokhfall, Farshad M Shirazi, Masoumeh Askari, Omid Mehrpour
Tramadol is an analgesic that has diverse pharmacological actions and a concomitant capability for numerous adverse effects. Blood glucose impairments, especially hypoglycemia, should be regarded as one of the consequential side effects of tramadol. Studies conducted on diabetic subjects universally reported hypoglycemia. Tramadol-induced hypoglycemia may be severe in some cases. Based on the results of this study, glycemic changes, particularly hypoglycemia, should be considered a potential side effect of tramadol use. Mechanisms of hypoglycemia due to tramadol may include 1. Activation of pancreatic opioid receptors. 2. Increased hepatic insulin sensitivity 3. A decrease in the liver’s expression of lPEPCK. 4. Activation of the insulin signaling pathway. 5. Increasing insulin receptor expression. 6. Activation of serotonin-induced increase in insulin concentrations. 7. The release of beta-endorphin. 8. Stimulation of glucose uptake by muscles. 9. Activation of peripheral opioid µ-receptors, which can increase glucose uptake. Very few studies evaluated tramadol-induced hyperglycemia, nor have they studied any possible tramadol dose effect. Therefore, conclusions regarding hyperglycemias should be regarded as speculative.