The Human Glomerular Podocyte Is a Novel Target for Insulin Action

Coward, Richard J M; Welsh, Gavin I.; Yang, Jing; Tasman, Candida; Lennon, Rachel; Koziell, Ania; Satchell, Simon C.; Holman, Geoffrey D.; Kerjaschki, Dontscho; Tavaré, Jeremy M.; Mathieson, Peter W.; Saleem, Moin A.

doi:10.2337/diabetes.54.11.3095

Cited by 256 publications

(245 citation statements)

References 37 publications

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“…We have recently reported that human glomerular podocytes are insulin-sensitive cells and are able to rapidly transport glucose using the glucose transporters GLUT4 and GLUT1 [17]. In addition, we have shown that this effect depends on the production of nephrin, which is required for GLUT1 translocation, in podocytes, [18].…”

Section: Introductionmentioning

confidence: 85%

“…The cells have additionally been transfected with a telomerase construct [20]. A podocyte cell line derived from a patient with Fin Major nephrin mutation was used and the characteristics of these podocytes have also been reported previously [17,19,21]. Cells were cultured for 14 days at the nonpermissive temperature (37°C) in RPMI 1640 medium with glutamine (R-8758; Sigma, St Louis, MO, USA) supplemented with 10% (vol./vol.)…”

Section: Methodsmentioning

confidence: 99%

“…ethanol (termed BSA). The dose of palmitate was based on previously published studies [27,28] 2-Deoxyglucose uptake assay The methods used were as previously reported [17]. Briefly, cells in six-well plates were pre-incubated accordingly before being serum starved in medium containing the required treatment for 2 h. For the final 15 min, cells were incubated in pre-warmed KrebsRinger phosphate buffer after washing three times in PBS.…”

Section: Methodsmentioning

confidence: 99%

“…GLUT1 small interfering RNA transfection As previously reported [17], a combination of two sequences was used with the following sense target sequences: CCAAGAGUGUG CUAAAGAAUU and CAUCGUGGCUGAACUCUUCUU. In addition, a non-specific control small interfering RNA (siRNA) sequence was used (Dharmacon, Lafayette, CO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…This method was performed as previously described [17,29], but with some modifications. Briefly, stimulated podocytes were incubated with and without 100 nmol/l insulin for 12 min and then incubated for a further 3 min in the presence of 200 μmol/l PEG-biotincap-ATB-BMPA (Toronto Research Chemical, Toronto, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

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Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1

et al. 2009

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Aims/hypothesis Peroxisome proliferator-activated receptor (PPAR) γ agonists are used increasingly in the treatment of type 2 diabetes. In the context of renal disease, PPARγ agonists reduce microalbuminuria in diabetic nephropathy; however, the mechanisms underlying this effect are unknown. Glomerular podocytes are newly characterised insulin-sensitive cells and there is good evidence that they are targeted in diabetic nephropathy. In this study we investigated the functional and molecular effects of the PPARγ agonist rosiglitazone on human podocytes. Methods Conditionally immortalised human podocytes were cultured with rosiglitazone and functional effects were measured with glucose-uptake assays. The effect of rosiglitazone on glucose uptake was also measured in 3T3-L1 adipocytes, nephrin-deficient podocytes, human glomerular endothelial cells, proximal tubular cells and podocytes treated with the NEFA palmitate. The role of the glucose transporter GLUT1 was investigated with immunofluorescence and small interfering RNA knockdown and the plasma membrane expression of GLUT1 was determined with bis-mannose photolabelling. Results Rosiglitazone significantly increased glucose uptake in wild-type podocytes and this was associated with translocation of GLUT1 to the plasma membrane. This effect was blocked with GLUT1 small interfering RNA. Nephrin-deficient podocytes, glomerular endothelial cells and proximal tubular cells did not increase glucose uptake in response to either insulin or rosiglitazone. Furthermore, rosiglitazone significantly increased basal and insulinstimulated glucose uptake when podocytes were treated with the NEFA palmitate. Conclusions/interpretation In conclusion, rosiglitazone has a direct and protective effect on glucose uptake in wild-type human podocytes. This represents a novel mechanism by which PPARγ agonists may improve podocyte function in diabetic nephropathy.

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Section: Introductionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1

et al. 2009

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The roles of melatonin on kidney injury in obese and diabetic conditions

Promsan

Lungkaphin

2020

BioFactors

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Obesity is a common and complex health problem worldwide and can induce the development of Type 2 diabetes. Chronic kidney disease (CKD) is a complication occurring as a result of obesity and diabetic conditions that lead to an increased mortality rate. There are several mechanisms and pathways contributing to kidney injury in obese and diabetic conditions. The expansion of adipocytes triggers proinflammatory cytokines release into blood circulation and bind with the receptors at the cell membranes of renal tissues leading to kidney injury. Obesity‐mediated inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction are the important causes and progression of CKD. Melatonin (N‐acetyl‐5‐methoxytryptamine) is a neuronal hormone that is synthesized by the pineal gland and plays an essential role in regulating several physiological functions in the human body. Moreover, melatonin has pleiotropic effects such as antioxidant, anti‐inflammation, antiapoptosis. In this review, the relationship between obesity, diabetic condition, and kidney injury and the renoprotective effect of melatonin in obese and diabetic conditions from in vitro and in vivo studies have been summarized and discussed.

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Glucose Homeostasis and Cardiovascular Alterations in Diabetes

Xiang

Mittwede

Clemmer

2015

Comprehensive Physiology

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Diabetes mellitus is an increasingly prevalent disease associated with a high morbidity and mortality burden. Many of the adverse outcomes secondary to diabetes occur as a result of the impaired glucose homeostasis and pathophysiological alterations to the cardiovascular system. The purpose of this overview is to broadly discuss many of the changes that occur in the context of diabetes that affect cardiovascular function. Following a brief introduction to the classification and etiologies of the various forms of diabetes, the mechanisms of impaired glucose homeostasis will be covered. Vascular endothelial dysfunction, which has been posited to play a major role in the development of target organ pathology, will be addressed, followed by a discussion of the effects of diabetes on the renal, cardiovascular, and pulmonary systems.

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The Human Glomerular Podocyte Is a Novel Target for Insulin Action

Cited by 256 publications

References 37 publications

Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1

Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1

The roles of melatonin on kidney injury in obese and diabetic conditions

Glucose Homeostasis and Cardiovascular Alterations in Diabetes

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