China
Africa
Explore chapters and articles related to this topic
Hypothalamic Neuronal Circuits Are Modulated by Insulin and Impact Metabolism 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Tadeu de Oliveira Diz, Sabela Casado, Rubén Nogueiras, Sulay Tovar
Insulin resistance is a condition characterized by a lack of cellular response, when the insulin receptor does not elicit a response, preventing the entry of glucose into the cell. This condition affects various insulin-sensitive tissues, such as adipose, muscle, liver, and also centrally, specifically in the hypothalamus (193). The emergence of insulin resistance is directly related to overnutrition, inflammatory processes and dysregulation of insulin signalling pathways (194). It is already known that a sedentary lifestyle and chronic excessive caloric intake can lead to insulin resistance (195, 196), and consequently, lead to the development of obesity, DM2, metabolic syndrome, visceral adiposity, cardio vascular disease, hypertension and fatty liver diseases (84, 197–199).
Ameliorating Insulin Signalling Pathway by Phytotherapy
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
The insulin receptor is a transmembrane receptor that is activated by insulin molecules (White and Kahn 1994). Two alpha subunits and two beta subunits make up the insulin receptor. The alpha subunits are involved in ligand binding, while the two intracellular tyrosine kinase beta-subunits participate in transducing the signal into the cell. The alpha subunits are linked by disulfide bonds to the beta subunits (Gustafson et al. 1999). Activation of the insulin receptor (IR) after ligand binding is a multi-step process involving structural changes in both the ligand and the receptor. The binding of insulin to IR results in autophosphorylation of the receptor on a number of crucial tyrosine residues. This causes activation of the insulin receptor tyrosine kinase, followed by phosphorylation of various insulin receptor substrate (IRS) proteins to propagate the insulin-signalling event further downstream and mediate various biological effects. The phosphorylation on tyrosine residues in IR and IRS proteins develops docking sites for other enzymes and effector molecules containing SH2 or phosphotyrosine-binding (PTB) domains to propagate insulin signal (Taha and Klip 1999). A schematic view of the role of PTP1B in metabolic insulin signalling pathway is depicted in Figure 15.1.
Fibrinolysis and Obesity
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Sergio Coccheri, Cristina Legnani
Insulin resistance is defined as the inability of insulin to exert a normal glucose disposal in peripheral tissues, as a result of target tissue abnormalities including insulin receptor and postreceptor defects. As a consequence of this condition, an increased amount of insulin is required to maintain normal glucose levels. Thus, insulin resistance is characterized by hyperinsulinemia in the presence of normal blood glucose levels; type II diabetes and hyperglycemia ensue when adequate compensation cannot be maintained. Insulin resistance is associated with a cluster of abnormalities, grouped under the term “syndrome X” or “insulin resistance syndrome”, including hyperinsulinemia, impaired glucose tolerance, obesity, especially of the abdominal type, hypertension, and changes in the lipoprotein pattern, with increased VLDL triglycerides and reduced HDL cholesterol. Three different prospective studies58-60 have found that insulin resistance is associated with an increased risk of cardiovascular disease.
Experimental and computational models to investigate intestinal drug permeability and metabolism
Published in Xenobiotica, 2023
Jinyuan Chen, Ziyun Yuan, Yifan Tu, Wanyu Hu, Cong Xie, Ling Ye
With developments in gene-editing technology, the application scope of in vivo models has been greatly expanded. Various gene-editing technologies have been used to knock out (to inactivate) or knock-in (overexpress) genes in animals to obtain models for specific studies (Majzoub and Muglia 1996; Glaeser and Fromm 2008). For example, genes that are not expressed in animals can be inserted and expressed using gene editing, avoiding the interspecies differences of conventional models. Gene-editing techniques are widely used in various fields, such as disease model construction, disease development studies, functional and mechanistic studies of drug transporters, and drug development (Schinkel et al. 1995; Kitamura et al. 2003; Glaeser and Fromm 2008). For example, Kitamura and colleagues used insulin receptor knockout mice to conduct in-depth studies on the functions of insulin receptors in various tissues (Kitamura et al. 2003). Moreover, P-gp knockout mice were used to study the effects of P-gp inhibitors on drug toxicity (Schinkel et al. 1995). Numerous studies have indicated the importance of gene-editing technology in the biological field. Research at the genetic level enables the investigation of the relevant mechanisms. As a result, the understanding of genes and proteins has increased and is no longer limited to superficial data. Gene-edited animal models are a useful tool that will likely be used to achieve key breakthroughs in the future.
Research progress of coumarins and their derivatives in the treatment of diabetes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yinbo Pan, Teng Liu, Xiaojing Wang, Jie Sun
Type II diabetes mellitus is one type of DM found in more than 90% of cases of DM and could be attributed to obesity, overweight and lack of physical activity, marked by pancreatic insulin release, when the body has not been trained to utilise insulin developed for glucose transfer, and the emergence of insulin resistance contributes to an increase of blood glucose or hyperglycaemia.88 Therefore, the insulin receptor is a potential target for screening the anti-diabetic ligand activity of insulin receptor activator, and it is a tyrosine kinase transmembrane receptor, which effectively participates in the regulation of glucose homeostasis through phosphorylation of insulin binding89–92. A total of 54 coumarin chalcone hybrids were synthesised by the famous Biginelli synthesis, Pechmann condensation, acetylation and Claisen-Schmidt reaction. Compared with diabetic rats treated with metformin (100 mg/kg b.d), further treatment with 80 and 81 at 30 mg/kg b.d. showed that MDA in pancreas and liver tissue of diabetic rats decreased significantly and moderately, while SOD and GSH rates increased89 (Figure 21).
Effects of aerobic exercise on waist circumference, VO2 max, blood glucose, insulin, and lipid index in middle-aged women: A meta-analysis of randomized controlled trials
Published in Health Care for Women International, 2022
Aerobic exercise increases fat breakdown through oxidation of fat during exercise through aerobic metabolism (Horowitz and Klein, 2000), so it lowers triglycerides and low-density lipoproteins and increases high-density lipoproteins (Kraus, et al., 2002; Galvao et al., 2011). As a result, it helps to reduce abdominal fat and improve cardiopulmonary function (Takeshima et al., 2004; Tang et al., 2013). In addition, aerobic exercise improves insulin resistance (Williams & Franklin, 2007). The reason is that insulin resistance is lowered and insulin sensitivity is increased by increasing the absorption of blood glucose into the muscle by increasing affinity with the insulin receptor substrate through regular and continuous muscle contraction (Dohm, 2002). As the amount of glycogen in the muscle increases to 50–65% of the maximum oxygen consumption, and at 85%, the amount of glycogen in the muscle doubles (Romijn, et al., 1993), it helps to improve insulin resistance (O'Donovan et al., 2005).