China
Africa
Explore chapters and articles related to this topic
Features of Lipid Metabolism in Diabetes Mellitus and Ischemic Heart Disease
Published in E.I. Sokolov, Obesity and Diabetes Mellitus, 2020
In accordance with the above mechanism (the Randle cycle), in the regulation of glycemia in a healthy person, the homeostatic and anabolic effect of insulin is 80–90 and 10–20%, respectively. The figures reverse in obesity patients — the homeostatic effect is 10–20%, and the anabolic one is 80–90%. It should be noted that insulin in an organism increases the synthesis of glycogen and protein from glucose 5–6 times, and of lipids — 10 times. This selective sensitivity of lipid metabolism to insulin underlies obesity and other pathologic states associated with hyperinsulinemia. Also, insulin regulates and modifies the activity of many enzymes only in the presence of glucose. Here enzymes such as hexokinase, glucokinase, glycogen-synthetase and glycogenphosphorylase, and pyruvatedehydrogenase are especially significant. The primary reaction of insulin with enzymes occurs on a plasmatic membrane without direct contact with the intracellular structures [493, 495, 515, 556].
Fat Distribution and Diabetes Mellitus
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Danae A. Delivanis, Michael D. Jensen
Skeletal muscle is the predominant organ of glucose disposal in the human body,149 thus muscle tissue dysfunction with respect to glucose uptake is central in the pathogenesis of insulin resistance. It is well documented that excess FFA results in reduced insulin sensitivity as measured by glucose uptake in skeletal muscle.150 One theory is through the preferential oxidation of fatty acids in comparison to glucose, resulting in a decrease of glucose uptake and oxidation (the Randle cycle).123 However, excess FFAs are also shown to interrupt muscle insulin receptor substrate-1 and its downstream signaling, resulting in impairment of insulin-mediated glucose uptake independent of muscle oxidative preferential substrate.151 Elevation of plasma FFA is thought to drive production of long-chain acyl-CoAs, ceramides, and diacylglycerols, some of the culprit molecules thought to disrupt insulin-mediated signaling.152 Considering that the majority of excess FFA is derived from upper-body subcutaneous adipose tissue, the upper-body subcutaneous fat depot is likely to be an important culprit for skeletal muscle–induced insulin resistance.153
Exercise, Nutrition, and Diabetes
Published in Jeffrey I. Mechanick, Elise M. Brett, Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
Philip Rabito, Jeffrey I. Mechanick, Elise M. Brett
Interestingly, after marathon running, insulin sensitivity is decreased in healthy subjects [27] despite low glycogen content and enhanced glycogen synthase activity. This is thought to be due to increased lipid oxidation and the inhibitory effect of fat utilization on glucose disposal (“Randle cycle”). Insulin clearance is enhanced after marathon running, which further spares glucose and allows enhanced lipid oxidation [28]. Eccentric exercise, which typically results in muscle damage, also induces a transient insulin resistance [29].
The influence of ketogenic therapy on the 5 R’s of radiobiology
Published in International Journal of Radiation Biology, 2019
Besides glycolysis, a second important adaption to high mtROS production frequently occurring in cancer cells is uncoupling of OXPHOS and ATP production through over-expression of uncoupling protein 2 (UCP2). This allows protons to leak from the intermembrane space back into the matrix, decreases the mitochondrial membrane potential and thus reduces the emission of mtROS (Mailloux & Harper 2011). UCP2 overexpression is considered a mechanism of RT and chemotherapy resistance and also has a metabolic action by supporting glucose and glutamine fermentation at the expense of mitochondrial oxidation (Vozza et al. 2014). However, this implicates inefficient mitochondrial ATP generation. Fine and colleagues have shown that UCP2 overexpression can be exploited therapeutically through administration of AcAc which led to ATP depletion and growth inhibition (Fine et al. 2009). They generally proposed that an ‘inefficient’ Randle cycle takes place in cancer cells in which glycolysis gets inhibited through free fatty acids and ketone bodies, but the cells would be unable to compensate for the reduced glycolytic ATP production due to uncoupling or general mitochondrial dysfunction.