Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish

Vanessa Schein,Luiz C Kucharski,Pedro M.G Guerreiro,Tiago Leal Martins,Isabel Morgado,Deborah M Power,Adelino V.M Canario,Roselis S.M Da Silva

doi:10.1016/j.mce.2015.07.010

Vanessa Schein, Luiz C Kucharski + Show 6 more

Open Access

https://doi.org/10.1016/j.mce.2015.07.010

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Abstract

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from 14C-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from 14C-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from 14C-acid lactic, while STC1-A increased gluconeogenesis from 14C-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes.

Highlights

In mammals, the kidney contributes to glucose homeostasis through the gluconeogenesis processes, glucose filtration, reabsorption, and consumption
The gluconeogenesis rate from 14C-glutamine in CX was not affected by the human STC1 (hSTC1) at any dose tested (Fig. 1A)
In the MD, the rate of glucose synthesis from 14C-glutamine was not modified by 0.01 ng/ml hSTC1 but it was 40% lower at 0.1 ng/ml (P < 0.05) when compared to the control group (Fig. 1A)

Summary

Introduction

The kidney contributes to glucose homeostasis through the gluconeogenesis processes, glucose filtration, reabsorption, and consumption. The kidney is responsible for up to 20% of all glucose production, contributing to about 40% of gluconeogenesis (Gerich et al, 2001; Mather and Pollock, 2011). While the poorly vascularized and relatively hypoxic renal medulla is a site of glycolysis, the renal cortex is a site of gluconeogenesis (Mather and Pollock, 2011). The proximal tubule is the only nephron segment that contains the key gluconeogenic enzymes. The net equilibrium of glucose is a balance between renal glucose release by the cortex and renal glucose uptake by the renal medulla (Gerich et al, 2001; Mather and Pollock, 2011)

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