Ameliorating Insulin Signalling Pathway by Phytotherapy
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in 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
Pia Glas-Greenwalt in Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
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.
Inhibiting the Absorption of Dietary Carbohydrates and Fats with Natural Products
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Insulin resistance in metabolic syndrome results, at least, from the overconsumption of dietary carbohydrates, cholesterol, and triglycerides leading to the formation of visceral adiposity, increased plasma-free fatty acids, and secretion of pro-inflammatory cytokines, which at cellular level decrease insulin receptor functionality also known as insulin resistance.1,2 Once insulin resistance is established, increased postprandial glycemia, according to genetic susceptibility, introduces the development of type 2 diabetes and cardiovascular insults.3–6 Thus, inhibiting the absorption of dietary carbohydrates and fats (cholesterol and triglycerides) with natural products or extracts of medicinal plants constitutes one therapeutic strategy to prevent or manage insulin resistance in metabolic syndrome.
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).
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
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