Autophagy and Mitochondria in Obesity and Type 2 Diabetes

Sarparanta, J.; García-Macia, Marina; Singh, Rajat

doi:10.2174/1573399812666160217122530

Cited by 134 publications

(90 citation statements)

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“…In skeletal muscle, the presence of damaged mitochondria generates oxidative stress and apoptosis, both of which can produce atrophy and muscular weakness [107]. Skeletal muscle from IR individuals has a higher degree of oxidative stress and toxic lipid intermediates accumulation, both conditions associated to mitochondrial damage [108]. Dynamin-related protein-1 (Drp-1) participates in mitochondrial fragmentation, which may result in mitochondrial dysfunction and IR [109].…”

Section: Findings On Insulin Resistance In Skeletal Musclementioning

confidence: 99%

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

Morales

Bucarey

Espinosa

2017

Journal of Diabetes Research

129

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Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA) availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR). In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN) family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

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Section: Findings On Insulin Resistance In Skeletal Musclementioning

confidence: 99%

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

Morales

Bucarey

Espinosa

2017

Journal of Diabetes Research

129

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“…It has been well accepted that autophagy plays an important role in the regulation of normal function of pancreatic β‐cells and insulin‐target tissues, such as skeletal muscle, liver, and adipose tissue (Barlow and Thomas, ). The role of molecular mechanisms underlying the regulation of autophagy process in the pathogenesis of T2DM has been highlighted during the past years (Rosa‐Caldwell et al, ; Sarparanta et al, ; Sato et al, ). Altered autophagic activity has been shown to be involved in the progression of obesity in T2DM through impaired β‐cell function and IR development (Barlow and Thomas, ).…”

Section: Introductionmentioning

confidence: 99%

Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy

Zhou

2018

Cell Biology International

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Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This study aimed to explore the effects of rapamycin, a specific inhibitor of kinase mammalian target of rapamycin (mTOR), on IR in T2DM rats, and to validate whether the underlying mechanism was associated with autophagy. In this study, the model of T2DM rats was established by feeding the animals with a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). Diabetic rats were randomly divided into model of T2DM control group (DM-C, n = 15), metformin group (DM-M, n = 15), rapamycin group (DM-Rapa, n = 15), 3-methyladenine (3-MA) group (DM-3-MA, n = 15), and rapamycin + 3-MA group (DM-Rapa-3-MA, n = 15). Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile, normal control group was established (n = 10). As expected, HFD- and STZ- induced T2DM rats exhibited significantly impaired glucose tolerance, reduced insulin sensitivity, dysglycemia and dyslipidemia, aggravated hepatic steatosis, enhanced hepatic inflammation, elevated p-mTOR, and suppressed hepatic autophagy. Importantly, rapamycin and metformin significantly ameliorated IR, relieved disorders of glucose and lipid metabolism, reduced inflammatory level, inhibited mTOR, and promoted autophagy. Importantly, the autophagy inhibitor 3-MA significantly reversed the effects exerted by rapamycin. Collectively, our study suggests that rapamycin improved IR and hepatic steatosis in T2DM rats via activation of autophagy.

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“…Autophagy plays a protective role in the immune response and in inflammation by regulating the transcriptional response to inflammatory stimuli, removing damaged mitochondria to reduce oxidative stress, regulating endoplasmic reticulum stress, and removing damaged organelles. Defects in autophagy can lead to inflammatory-related metabolic diseases, such as diabetes and obesity [64]. In the mouse liver, inhibition of the autophagy gene Atg7 leads to endoplasmic reticulum stress and insulin resistance [65].…”

Section: (C) Immunity and Inflammationmentioning

confidence: 99%

Aberrant regulation of autophagy in mammalian diseases

Xie

Zhou

2018

Biol. Lett.

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Autophagy is a major cellular metabolic pathway that facilitates degradation of a subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells. This pathway plays a vital role in preserving the cellular homeostasis of the cells themselves, in addition to maintaining the normal physiological state of cell renewal. Many stressors, such as starvation, ischaemia and oxidative stress can induce autophagy. In addition to its physiological roles, autophagy also occurs in a wide variety of pathological processes, including tumour progression, metabolic disorders, and neurodegenerative and lung diseases. In recent years, a growing body of evidence has shown that autophagy also plays a key role in the development of mammalian diseases, a function that has garnered substantial attention and study. An in-depth understanding of the molecular role that autophagy plays in pathological settings is vital for both the diagnosis and treatment of mammalian diseases and will aid in the search for novel targets for therapeutic drug intervention. Here, we provide an integrated review of recent studies implicating autophagy dysfunction in the progression of mammalian disorders and summarize research suggesting that the molecular pathways involved in autophagy could serve as potential therapeutic targets.

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Autophagy and Mitochondria in Obesity and Type 2 Diabetes

Abstract: Here we explore the connections of autophagy with mitochondria in obesity and type 2 diabetes, and discuss its roles in diabetic complications. Understanding how autophagy protects against diabetes could help design new strategies against this growing epidemic.

Cited by 134 publications

References 0 publications

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy

Aberrant regulation of autophagy in mammalian diseases

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