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Insulin Signaling Modulates Neuronal Metabolism
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Qian Huang, Jialin Fu, Kelly Anne Borges, Weikang Cai
Insulin is the central hormone in the regulation of glucose homeostasis and energy balance in the body. While the brain is traditionally considered an insulin-insensitive organ, it is now more and more clear that insulin acts on almost all cell types in the brain to modulate brain metabolism and neural functions. Although insulin has moderate effects on glucose uptake in the brain, it plays critical role in many aspects of cellular metabolism in neurons, including glucose oxidation, glycogen synthesis, and lipid synthesis. In addition, insulin signaling is particularly important for the homeostasis of both mitochondria and ER, and their functions in neurons. Thus, insulin shows beneficial effects on ER-related calcium homeostasis, and mitochondrial-dependent cellular processes, including increasing respiration rates and ATP production, promoting protein homeostasis, and decreasing oxidative stress and mitochondrial-initiated cellular apoptosis. Conversely, in the context of diabetes and neurodegenerative diseases such as AD, impaired insulin signaling in neurons leads to mitochondrial dysfunction, calcium signaling imbalance, and metabolic disturbance, all of which contribute to the further exacerbation of cellular stresses harmful to neurons, leading to the deterioration of normal neural functions. Therefore, it is of utmost importance to continue to uncover the molecular linkage between neuronal insulin signaling and neuronal metabolism, aiming to identify potential therapeutic targets to alleviate or treat neurological symptoms caused by diabetes and neurodegeneration.
Exercise Redox Signalling
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Ruy A. Louzada, Jessica Bouviere, Rodrigo S. Fortunato, Denise P. Carvalho
Skeletal muscle is one of the crucial tissues involved in glucose homeostasis. Regardless of exercise stimulation, upon insulin action, NOX-derived ROS is required for the increase of intracellular Ca2+, which is mediated by the IP3 receptor. This process is involved in the transport of vesicles containing GLUT4 to the plasma membrane (da Justa Pinheiro et al., 2010; Silveira et al., 2006). Adding H2O2 directly to a muscle cell increases glucose uptake through the PI3K signalling pathway. Moreover, pretreatment with ROS scavengers (e.g., catalase and superoxide dismutase (SOD)) blunted the muscle glucose uptake induced by muscle contraction (Higaki et al., 2008; Katz, 2007), showing that the ROS produced during contractile activity is involved in glucose uptake.
Digestive and Metabolic Actions of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The insulin-secreting beta cells, which make up 70%–80% of the islet cells, have all the components necessary for DA synthesis, secretion, and action. Insulin is primarily released in response to elevated blood glucose levels, and its actions are fundamental to the maintenance of glucose homeostasis [60]. Binding to its glycoprotein receptor, insulin is the only hormone that lowers blood glucose levels by promoting glucose uptake by the various cells. The opposite effects (i.e., glycogenolysis and gluconeogenesis) are partly under the control of glucagon. The role of the pancreatic polypeptide in metabolism is unclear except that it serves as a satiety hormone. The main effect of somatostatin on metabolism is via its inhibition of GH, a major metabolic hormone.
Kolaviron modulates dysregulated metabolism in oxidative pancreatic injury and inhibits intestinal glucose absorption with concomitant stimulation of muscle glucose uptake
Published in Archives of Physiology and Biochemistry, 2023
Veronica F. Salau, Ochuko L. Erukainure, Neil A. Koorbanally, Md. Shahidul Islam
To further buttress the inhibitory potential of kolaviron as an antidiabetic agent, the intestinal glucose absorption in rat jejunum and skeletal muscle glucose uptake were investigated. The rate of glucose absorption in the small intestine which is known to be highest at the joining of the duodenum to the jejunum has a major impact on postprandial glucose level (Chukwuma et al.2018). From our result (Figure 4), intestinal glucose absorption was strongly inhibited dose-dependently with increasing concentration of kolaviron as against the control which was not incubated with kolaviron. Muscle glucose uptake is actively involved in glucose homeostasis. Insulin, through the help of glucose transporter 4 (GLUT 4), stimulates uptake of glucose from the blood to target organs such as the muscle (Alvim et al.2015, Pereira et al.2017). However, skeletal muscle glucose uptake is impaired in the development and progression of type 2 diabetes as a result of insulin resistance which leads to sustained hyperglycaemia (Chukwuma et al.2018). In this study, the increased glucose uptake in muscles incubated with kolaviron (Figure 5) indicates the ability of the flavonoid to decrease hyperglycaemia. This corroborates its inhibitory property on carbohydrate digesting enzymes, thus confirming the antidiabetic potential of kolaviron.
Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era
Published in Gut Microbes, 2022
Yoscelina Estrella Martínez-López, Diego A. Esquivel-Hernández, Jean Paul Sánchez-Castañeda, Daniel Neri-Rosario, Rodolfo Guardado-Mendoza, Osbaldo Resendis-Antonio
Glucose homeostasis is the product of metabolic, hormonal, neural, and microbial signals whose regulation determines the degree of glucose-dependent insulin release. The progression from normoglycemia to glucose intolerance and later to T2D occurs due to a deterioration in these signals, which gradually decreases insulin sensitivity and β-cell functionality (Figure 2b).2 This dysfunction associated with GM can be induced by two effects: 1) the increase in intestinal permeability; and 2) the chronically elevated glucose levels in the host (islet glucotoxicity).53 This physiological imbalance causes an increase in intestinal permeability, which in turn promotes the translocation of some bacteria (Proteus mirabilis and Escherichia coli) and their metabolites.54 To respond to intestinal permeability in the host, two main detection systems continuously scan for bacteria capable of translocating the intestinal mucosa or adhering to the epithelium: 1) NOD-like receptors (NLRs), which detect the presence of intracellular microbes; and 2) TLRs.38
Molecular and cellular biology of PCSK9: impact on glucose homeostasis
Published in Journal of Drug Targeting, 2022
Sègbédé E. R. Tchéoubi, Casimir D. Akpovi, Frédérique Coppée, Anne-Emilie Declèves, Sophie Laurent, Clément Agbangla, Carmen Burtea
Glucagon is another important hormone involved in glucose homeostasis, T2DM pathogenesis [128, 129] and lipid regulation [130]. Its relationship with PCSK9 was pointed out by Spolitu et al. when investigating the role of glucagon receptor (Gcgr) in plasma cholesterol regulation [128]. The authors demonstrated that mice injected with glucagon exhibited decreased plasma PCSK9 and LDL-c levels without change in VLDL-c, HDL-c or body weight compared to controls. As expected, Gcgr silencing or blocking lowered blood glucose level and increased plasma PCSK9 level. However, no change was observed in hepatic PCSK9, LDLR and their transcription factors HNF-1α and SREBP2 at the mRNA level. They reported that Gcgr signalling modulates PCSK9 through its lysosomal degradation and the exchange protein directly activated by the cAMP-2 (Epac2) and Ras-related protein-1 (Rap1) pathway.