scholarly journals GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 154
Author(s):  
Rajagopal V. Sekhar
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Plasma Ffa ◽  
Underlying Mechanisms

Patients with type 2 diabetes (T2D) are known to have mitochondrial dysfunction and increased insulin resistance (IR), but the underlying mechanisms are not well understood. We reported previously that (a) adequacy of the antioxidant glutathione (GSH) is necessary for optimal mitochondrial fatty-acid oxidation (MFO); (b) supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC) in mice corrected GSH deficiency, reversed impaired MFO, and lowered oxidative stress (OxS) and IR; and (c) supplementing GlyNAC in patients with T2D improved GSH synthesis and concentrations, and lowered OxS. However, the effect of GlyNAC on MFO, MGO (mitochondrial glucose oxidation), IR and plasma FFA (free-fatty acid) concentrations in humans with T2D remains unknown. This manuscript reports the effect of supplementing GlyNAC for 14-days on MFO, MGO, IR and FFA in 10 adults with T2D and 10 unsupplemented non-diabetic controls. Fasted T2D participants had 36% lower MFO (p < 0.001), 106% higher MGO (p < 0.01), 425% higher IR (p < 0.001) and 76% higher plasma FFA (p < 0.05). GlyNAC supplementation significantly improved fasted MFO by 30% (p < 0.001), lowered MGO by 47% (p < 0.01), decreased IR by 22% (p < 0.01) and lowered FFA by 25% (p < 0.01). These results provide proof-of-concept that GlyNAC supplementation could improve mitochondrial dysfunction and IR in patients with T2D, and warrant additional research.

scholarly journals Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes-Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Muhammad Sohail Khan ◽  
Muhammad Ikram ◽  
Tae Ju Park ◽  
Myeong Ok Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Acid Oxidation ◽  
Chronic Hyperglycemia ◽  
Underlying Mechanisms

The pathology and neurodegeneration in type 2 diabetes- (T2D-) mediated Alzheimer’s disease (AD) have been reported in several studies. Despite the lack of information regarding the basic underlying mechanisms involved in the development of T2D-mediated AD, some common features of the two conditions have been reported, such as brain atrophy, reduced cerebral glucose metabolism, and insulin resistance. T2D phenotypes such as glucose dyshomeostasis, insulin resistance, impaired insulin signaling, and systemic inflammatory cytokines have been shown to be involved in the progression of AD pathology by increasing amyloid-beta accumulation, tau hyperphosphorylation, and overall neuroinflammation. Similarly, oxidative stress, mitochondrial dysfunction, and the generation of advanced glycation end products (AGEs) and their receptor (RAGE) as a result of chronic hyperglycemia may serve as critical links between diabetes and AD. The natural dietary polyflavonoid anthocyanin enhances insulin sensitivity, attenuates insulin resistance at the level of the target tissues, inhibits free fatty acid oxidation, and abrogates the release of peripheral inflammatory cytokines in obese (prediabetic) individuals, which are responsible for insulin resistance, systemic hyperglycemia, systemic inflammation, brain metabolism dyshomeostasis, amyloid-beta accumulation, and neuroinflammatory responses. In this review, we have shown that obesity may induce T2D-mediated AD and assessed the recent therapeutic advances, especially the use of anthocyanin, against T2D-mediated AD pathology. Taken together, the findings of current studies may help elucidate a new approach for the prevention and treatment of T2D-mediated AD by using the polyflavonoid anthocyanin.

Lipid metabolism, exercise and insulin action

2006 ◽  
Vol 42 ◽  
pp. 47-59 ◽  
Author(s):  
Arend Bonen ◽  
G. Lynis Dohm ◽  
Luc J.C. van Loon
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Insulin Signalling ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Severely Obese

Skeletal muscle constitutes 40% of body mass and takes up 80% of a glucose load. Therefore, impaired glucose removal from the circulation, such as that which occurs in obesity and type 2 diabetes, is attributable in large part to the insulin resistance in muscle. Recent research has shown that fatty acids, derived from adipose tissue, can interfere with insulin signalling in muscle. Hence, insulin-stimulated GLUT4 translocation to the cell surface is impaired, and therefore, the rate of glucose removal from the circulation into muscle is delayed. The mechanisms provoking lipid-mediated insulin resistance are not completely understood. In sedentary individuals, excess intramyocellular accumulation of triacylglycerols is only modestly associated with insulin resistance. In contrast, endurance athletes, despite accumulating large amounts of intramyocellular triacylglycerols, are highly insulin sensitive. Thus it appears that lipid metabolites, other than triacylglycerols, interfere with insulin signalling. These metabolites, however, are not expected to accumulate in athletic muscles, as endurance training increases the capacity for fatty acid oxidation by muscle. These observations, and others in severely obese individuals and type 2 diabetes patients, suggest that impaired rates of fatty acid oxidation are associated with insulin resistance. In addition, in obesity and type 2 diabetes, the rates of fatty acid transport into muscle are also increased. Thus, excess intracellular lipid metabolite accumulation, which interferes with insulin signalling, can occur as a result of impaired rates of fatty acid oxidation and/or increased rates of fatty acid transport into muscle. Accumulation of excess intramyocellular lipid can be avoided by exercise, which improves the capacity for fatty acid oxidation.

scholarly journals Fatty acid metabolism in obesity and type 2 diabetes mellitus

2003 ◽  
Vol 62 (3) ◽  
pp. 753-760 ◽  
Author(s):  
E. E. Blaak
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Acid Oxidation ◽  
Acid Uptake

Disturbances in pathways of lipolysis and fatty acid handling are of importance in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that a lowered catecholamine-mediated lipolytic response may play a role in the development and maintenance of increased adipose tissue stores. Increased adipose tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high lipolytic rate may increase circulating NEFA concentrations, which may promote insulin resistance and cardiovascular complications. In addition, a disturbance of NEFA uptake by adipose tissue postprandially is also a critical determinant of plasma NEFA concentration. Furthermore, evidence is increasing that insulin-resistant muscle is characterised by a lowered ability to oxidise fatty acids. A dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a factor promoting accumulation of lipid intermediates and triacylglycerols within skeletal muscle, which is strongly associated with skeletal muscle insulin resistance. The present review describes the reported disturbances in pathways of lipolysis and skeletal muscle fatty acid handling, and discusses underlying mechanisms and metabolic consequences of these disturbances.

scholarly journals Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

Aging Cell ◽  
2013 ◽  
Vol 12 (3) ◽  
pp. 415-425 ◽  
Author(s):  
Dan Nguyen ◽  
Susan L. Samson ◽  
Vasumathi T. Reddy ◽  
Erica V. Gonzalez ◽  
Rajagopal V. Sekhar
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Protective Role ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

scholarly journals Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4667-4676 ◽  
Author(s):  
Lisa Héron-Milhavet ◽  
Martin Haluzik ◽  
Shoshana Yakar ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Function ◽  
Dominant Negative ◽  
Whole Body ◽  
Acid Oxidation

Abstract Insulin resistance is one of the primary characteristics of type 2 diabetes. Mice overexpressing a dominant-negative IGF-I receptor specifically in muscle (MKR mice) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5–6 wk of age. To determine whether lipotoxicity plays a role in the progression of the disease, we crossed MKR mice with mice overexpressing a fatty acid translocase, CD36, in skeletal muscle. The double-transgenic MKR/CD36 mice showed normalization of the hyperglycemia and the hyperinsulinemia as well as a marked improvement in liver insulin sensitivity. The MKR/CD36 mice also exhibited normal rates of fatty acid oxidation in skeletal muscle when compared with the decreased rate of fatty acid oxidation in MKR. With the reduction in insulin resistance, β-cell function returned to normal. These and other results suggest that the insulin resistance in the MKR mice is associated with increased muscle triglycerides levels and that whole-body insulin resistance can be, at least partially, reversed in association with a reduction in muscle triglycerides levels, although the mechanisms are yet to be determined.

scholarly journals Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes

2019 ◽  
Vol 20 (5) ◽  
pp. 1216 ◽  
Author(s):  
Seok Seo ◽  
Sang-Mi Jo ◽  
Jiyoung Kim ◽  
Myoungsook Lee ◽  
Yunkyoung Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Triglyceride Accumulation ◽  
Mitochondrial Fatty Acid ◽  
Adipocyte Cell ◽  
Underlying Mechanisms

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [3H]-oleic acid (OA) to [3H]-H2O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation.

Glucocorticoids promote mitochondrial fatty acid oxidation in the fetal heart

2019 ◽  
Author(s):  
Helena Urquijo ◽  
Emma N Panting ◽  
Roderick N Carter ◽  
Emma J Agnew ◽  
Caitlin S Wyrwoll ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fetal Heart ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid
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