Tag Archives: Kidney

Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney

Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium–glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. In contrast, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor. In the HK-2 cells, the gluconeogenic gene expression was suppressed by insulin, accompanied by phosphorylation and inactivation of forkhead box transcription factor 1 (FoxO1). In contrast, glucose deacetylated peroxisome proliferator–activated receptor coactivator 1-α (PGC1α), a coactivator of FoxO1, via sirtuin 1, suppressing the gluconeogenic gene expression, which was reversed by inhibition of glucose reabsorption. These data suggest that both insulin signaling and glucose reabsorption suppress the gluconeogenic gene expression by inactivation of FoxO1 and PGC1α, respectively, providing insight into novel mechanisms underlying the regulation of gluconeogenesis in the PTs.

Diabetes Journal current issue





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Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2 Diabetes: A Case Series

Harindra Rajasekeran
Jul 1, 2017; 40:e75-e76
e-Letters: Observations
: Most-Read Full-Text Articles





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SGLT2 Inhibitors and the Diabetic Kidney

Paola Fioretto
Aug 1, 2016; 39:S165-S171
III. SGLT2 Therapy
: Most-Read Full-Text Articles





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Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease

The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of renal prognosis in diabetes and may not be the primary event in the development of diabetic kidney disease either. Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current “glomerulocentric” paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state. Such findings raise important issues for therapeutic advances specifically targeting the pathophysiological perturbations that develop in this part of the nephron.

Diabetes Journal current issue





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Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney

Diabetes Journal current issue





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SGLT2 Inhibitors and the Diabetic Kidney

Paola Fioretto, Alberto Zambon, Marco Rossato, Luca Busetto, Roberto Vettor
Aug 1, 2016; 39:165-171
III. SGLT2 Therapy
Diabetes Care: Most-Read Full-Text Articles





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Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON

Muh Geot Wong, Vlado Perkovic, John Chalmers, Mark Woodward, Qiang Li, Mark E. Cooper, Pavel Hamet, Stephen Harrap, Simon Heller, Stephen MacMahon, Giuseppe Mancia, Michel Marre, David Matthews, Bruce Neal, Neil Poulter, Anthony Rodgers, Bryan Williams, Sophia Zoungas, for the ADVANCE-ON Collaborative Group
May 1, 2016; 39:694-700
Cardiovascular Disease and Diabetes
Diabetes Care: Most-Read Full-Text Articles





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The Hypothalamic Melanocortin Pathway and the Regulation of Glucose Handling in the Kidney: A Sympathetic Look at Brain-Kidney Connection

Diabetes Journal current issue





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