Free Fatty Acids and Skeletal Muscle Insulin Resistance

Rachek, Lyudmila I.

doi:10.1016/b978-0-12-800101-1.00008-9

Cited by 118 publications

(86 citation statements)

References 131 publications

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“…Several factors have been implicated as the major defects responsible for IR in muscle tissues during the progression of T2DM, among which FFA was taken as a key point in recent studies [38, 39]. It has been generally recognized that a lack of exercise is an important cause of T2DM, and proper movement is a meaningful strategy for treating T2DM.…”

Section: Discussionmentioning

confidence: 99%

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice

Fang

Zhao

et al. 2017

PLoS ONE

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Jiang Tang Xiao Ke (JTXK) granule, a Chinese herbal formula, has been used clinically to treat type 2 diabetes (T2DM) for decades. Our previous studies showed that JTXK granule exhibited anti-diabetic and anti-oxidative functions in experimental diabetic rats induced by a high fat diet and streptozotocin. However, the underlying mechanisms remain poorly understood. Herein, we aimed to investigate the therapeutic effect of JTXK granule on T2DM KKAy mice and the possible associations with skeletal muscle in the current study. Our results showed that JTXK granule significantly reduced food intake and body weight in T2DM KKAy mice. JTXK granule treatment also decreased the blood glucose and HbA1c levels and increased the insulin sensitivity in a time-dependent manner. Additionally, it ameliorated hyperlipidaemia and induced a lower free fatty acid level, displaying an effect on disorders of lipid metabolism. JTXK granule significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/Akt) and glucose transporter 4 (Glut4) and decreased the expression of glycogen synthase kinase 3β (GSK3β). We concluded that JTXK granule is an effective drug for T2DM through regulating the PI3K/Akt signalling pathway in skeletal muscle.

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Section: Discussionmentioning

confidence: 99%

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice

Fang

Zhao

et al. 2017

PLoS ONE

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“…Elevated free fatty acids impair insulin signaling and cause subclinical inflammation with subsequent pancreatic beta-cell dysfunction. 107,115,116 Free fatty acid elevation may also be involved in terminal arrhythmias 117 and induction of a prothrombotic state. 118 The CETP inhibitor torcetrapib raises HDL-cholesterol concentration but also improves hyperglycemia.…”

Section: Mechanisms Of Increased Ascvd Risk and Mortality In Type 2 Dmentioning

confidence: 99%

Clinical Update: Cardiovascular Disease in Diabetes Mellitus

et al. 2016

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Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multi-factorial risk reduction with statins and other lipid lowering agents, anti-hypertensive therapies, and anti-hyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes than for those without. This review considers the mechanisms, history, controversies, new pharmacologic agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes and heart disease outside of the acute care setting.

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“…Similarly, mice overexpressing diacylglycerol (DAG) acyltransferase 1 accumulate triacylglycerides (TG) and retain insulin sensitivity in combination with reduced DAG and ceramide levels [16]. This suggests that accumulation of TG in muscle can be a physiological condition, whereas accumulation of intermediate lipid metabolites, such as DAG, impair normal physiological function [17]. …”

Section: Introductionmentioning

confidence: 99%

Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men

et al. 2018

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Insulin resistance is a well-known physiological adaptation to prolonged fasting in healthy skeletal muscle. Obesity is associated with insulin resistance and metabolic inflexibility in skeletal muscle, and a pronounced increase in the risk of metabolic complications. Under the hypothesis that the metabolic traits of insulin resistance associated with prolonged fasting are different from insulin resistance associated with obesity, we examined nine obese and nine lean participants during 12 and 72h of fasting, respectively. Insulin resistance in obese participants was associated with impaired insulin signaling, and reduced levels of glucose-6-phosphate and TCA-cycle intermediates. 72h of fasting in lean participants reduced insulin-stimulated glucose uptake to levels similar to obese participants fasted for 12h. This was associated with increased lipid oxidation, but not accumulation of diacylglycerol or acylcarnitines and impairment of insulin signaling. Prolonged fasting was associated with pronounced increases in β-hydroxybutyrate and β- hydroxybutyrylcarnitine levels in skeletal muscle suggesting augmented ketone body metabolism. Fasting induced insulin resistance may be a consequence of substrate competition. The underlying mechanism behind insulin resistance in obesity is thus not comparable to the physiological adaptations in skeletal muscle induced by prolonged fasting in lean participants.

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Free Fatty Acids and Skeletal Muscle Insulin Resistance

Cited by 118 publications

References 131 publications

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice

Clinical Update: Cardiovascular Disease in Diabetes Mellitus

Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men

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