Activation of the renal renin-angiotensin system in diabetes--new concepts - PubMed (original) (raw)

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Activation of the renal renin-angiotensin system in diabetes--new concepts

János Peti-Peterdi et al. Nephrol Dial Transplant. 2008 Oct.

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Figures

Fig. 1

Fig. 1

Schematic illustration of the newly described (juxta)glomerular paracrine signaling cascade involving succinate activation of GPR91, leading to renin synthesis and release. High glucose levels result in the accumulation of the metabolic intermediate succinate, which acts directly on the vascular endothelium and triggers cell-to-cell signaling to culminate in renin release from the juxtaglomerular apparatus. The chain of events involves elevating glucose levels, succinate accumulation in the plasma and local interstitium, GPR91 activation, increases in endothelial cytosolic calcium, nitric oxide (NO) and prostaglandin (at least PGE2) production and release from endothelium, PG actions on renin-producing JG cells, renin release, angiotensin (Ang I and Ang II) synthesis and RAS activation. Endothelial NO and PG production also causes vasodilatation that may be important in the development of glomerular hyperfiltration.

Fig. 2

Fig. 2

The two major sites of intra-renal (pro)renin synthesis: the juxtaglomerular apparatus (JGA) and the collecting duct (CD). Schematic drawing (A) and in vivo multi-photon fluorescence images (B, C) of these two sites. Direct in vivo visualization of quinacrine-labeled renin granules (green) in the JGA (B) and CD (C) in the intact kidney using multi-photon confocal microscopy. Control rat (B) and diabetic mouse kidney (C) are shown. A dextran-rhodamine B conjugate (70 kDa) labeled the intravascular space (plasma) red. (B) Quinacrine identified JGA renin granules in the terminal afferent arteriole (AA). The efferent arteriole (EA) is seen leaving the glomerulus (G). (C) Note the abundance of quinacrine staining in the bulging apical aspects of CD principal cells in diabetes (arrows). Nuclei are labeled blue with Hoechst 33342. Bars are 20 μm. MD: macula densa; CNT: connecting tubule; PTC: peritubular capillaries.

References

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