Aquaporins in insulin resistance and diabetes: More than channels!

Galli, M; Hameed, Ahsan; Żbikowski, Arkadiusz; Zabielski, Piotr

doi:10.1016/j.redox.2021.102027

Cited by 24 publications

(10 citation statements)

References 135 publications

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“…These impacts lead to enhanced levels of fatty acid and free glycerol associated with insulin resistance. 155 Recent experiments have focused on the application of nanostructures in reversing insulin resistance. The MgO nanostructures have the capacity of decreasing insulin resistance up to 29.5%.…”

Section: Exosomes and Insulin Resistancementioning

confidence: 99%

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Ashrafizadeh¹,

Kumar²,

Aref³

et al. 2022

IJN

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Diabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30-150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of β cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and β-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.

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Section: Exosomes and Insulin Resistancementioning

confidence: 99%

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Ashrafizadeh¹,

Kumar²,

Aref³

et al. 2022

IJN

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“…The coordinated regulation of the two channels leads to the optimum balance between release of glycerol through AQP7 by adipose tissue and its uptake through AQP9 by the liver [ 22 , 36 , 37 ]. Up-regulation of adipose AQP7 and down-regulation of hepatic AQP9 was connected with insulin resistance [ 38 ]. Therefore, the insulin resistance identified in AQP9 −/− hepatocytes may involve both oxidative stress and metabolic disorders due to impaired export of H 2 O 2 and insufficient uptake of glycerol.…”

Section: Resultsmentioning

confidence: 99%

Aquaporin-9 facilitates liver regeneration following hepatectomy

Zhang

Yang

et al. 2022

Redox Biology

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Aquaporin-9 (AQP9) is an aquaglyceroporin strongly expressed in the basolateral membrane of hepatocytes facing the sinusoids. AQP9 is permeable to hydrogen peroxide (H 2 O 2 ) and glycerol as well as to water. Here, we report impaired liver regeneration in AQP9 −/− mice which involves altered steady-state H 2 O 2 concentration and glucose metabolism in hepatocytes. AQP9 −/− mice showed remarkably delayed liver regeneration and increased mortality following 70% or 90% partial hepatectomy. Compared to AQP9 +/+ littermates, AQP9 −/− mice showed significantly greater hepatic H 2 O 2 concentration and more severe liver injury. Fluorescence measurements indicated impaired H 2 O 2 transport across plasma membrane of primary cultured hepatocytes from AQP9 −/− mice, supporting the hypothesis that AQP9 deficiency results in H 2 O 2 accumulation and oxidative injury in regenerating liver because of reduced export of intracellular H 2 O 2 from hepatocytes. The H 2 O 2 overload in AQP9 −/− hepatocytes reduced PI3K-Akt and insulin signaling, inhibited autophagy and promoted apoptosis, resulting in impaired proliferation and increased cell death. In addition, hepatocytes from AQP9 −/− mice had low liver glycerol and high blood glycerol levels, suggesting decreased glycerol uptake and gluconeogenesis in AQP9 −/− hepatocytes. Adeno-associated virus (AAV)-mediated expression of hepatic expression of aquaglyceroporins AQP9 and AQP3 in AQP9 −/− mice, but not water-selective channel AQP4, fully rescued the impaired liver regeneration phenotype as well as the oxidative injury and abnormal glucose metabolism. Our data revealed a pivotal role of AQP9 in liver regeneration by regulating hepatocyte H 2 O 2 homeostasis and glucose metabolism, suggesting AQP9 as a novel target to enhance liver regeneration following injury, surgical resection or transplantation.

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“…Aquaglyceroporins (AQP) are transmembrane channels permeable to water, glycerol, urea, and other small non-charged or bipolar solutes ( 210 , 211 ). AQP7 and AQP9 are mainly expressed in the adipose tissue and the liver, respectively ( 212 ). In these tissues, AQP7 and AQP9 participate in glycerol transport and participate in the development of insulin resistance ( 212 , 213 ).…”

Section: The Effects Of Arsenic On Ionic Channel Function As a Mechan...mentioning

confidence: 99%

“…AQP7 and AQP9 are mainly expressed in the adipose tissue and the liver, respectively ( 212 ). In these tissues, AQP7 and AQP9 participate in glycerol transport and participate in the development of insulin resistance ( 212 , 213 ). Also, AQP7 is expressed in normal and tumoral pancreatic β-cells, and the existing data suggest that it plays a role in GSIS ( 214 , 215 ).…”

Section: The Effects Of Arsenic On Ionic Channel Function As a Mechan...mentioning

confidence: 99%

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

et al. 2022

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Exposure to arsenic in drinking water is a worldwide health problem. This pollutant is associated with increased risk of developing chronic diseases, including metabolic diseases. Metabolic syndrome (MS) is a complex pathology that results from the interaction between environmental and genetic factors. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, and cancer. The MS includes at least three of the following signs, central obesity, impaired fasting glucose, insulin resistance, dyslipidemias, and hypertension. Here, we summarize the existing evidence of the multiple mechanisms triggered by arsenic to developing the cardinal signs of MS, showing that this pollutant could contribute to the multifactorial origin of this pathology.

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Aquaporins in insulin resistance and diabetes: More than channels!

Cited by 24 publications

References 135 publications

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Aquaporin-9 facilitates liver regeneration following hepatectomy

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

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