Glomerulotubular balance, dietary protein, and the renal response to glycine in diabetic rats

2002 ◽  
Vol 282 (4) ◽  
pp. R1096-R1103 ◽  
Author(s):  
Larry A. Slomowitz ◽  
Aihua Deng ◽  
John S. Hammes ◽  
Francis Gabbai ◽  
Scott C. Thomson
Keyword(s):  
Dietary Protein ◽  
Distal Tubule ◽  
Diabetic Rats ◽  
Tubular Reabsorption ◽  
Protein Restriction ◽  
Tubuloglomerular Feedback ◽  
Vascular Effect ◽  
Dietary Protein Restriction ◽  
Single Nephron ◽  
Renal Micropuncture

The glomerular filtration rate (GFR) normally increases during glycine infusion, which is a test of “renal reserve.” Renal reserve is absent in diabetes mellitus. GFR increases after protein feeding because of increased tubular reabsorption, which reduces the signal for tubuloglomerular feedback (TGF). Dietary protein restriction normalizes some aspects of glomerular function in diabetes. Renal micropuncture was performed in rats 4–5 wk after diabetes was induced by streptozotocin to determine whether renal reserve is lost as a result of altered tubular function and activation of TGF, whether 10 days of dietary protein restriction could restore renal reserve, and whether this results from effects of glycine on the tubule. TGF activation was determined by locating single-nephron GFR (SNGFR) in the early distal tubule along the TGF curve. The TGF signal was determined from the ionic content of the early distal tubule. In nondiabetic rats, SNGFR in the early distal tubule increased during glycine infusion because of primary vasodilation augmented by increased tubular reabsorption, which stabilized the TGF signal. In diabetic rats, glycine reduced reabsorption, thereby activating TGF, which was largely responsible for the lack of renal reserve. In protein-restricted diabetic rats, the tubular response to glycine remained abnormal, but renal reserve was restored by a vascular mechanism. Glycine affects GFR directly and via the tubule. In diabetes, reduced tubular reabsorption dominates. In low-protein diabetes, the vascular effect is enhanced and overrides the effect of reduced tubular reabsorption.

scholarly journals Glomerular Hyperfiltration in Experimental Diabetes Mellitus

1999 ◽  
Vol 10 (12) ◽  
pp. 2569-2576
Author(s):  
VOLKER VALLON ◽  
KERSTIN RICHTER ◽  
ROLAND C. BLANTZ ◽  
SCOTT THOMSON ◽  
HARTMUT OSSWALD
Keyword(s):  
Diabetes Mellitus ◽  
Distal Tubule ◽  
Diabetic Rats ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Glomerular Hyperfiltration ◽  
Feedback Signal ◽  
Early Diabetes ◽  
Nondiabetic Control ◽  
Single Nephron

Abstract. An increase in Na+/glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a greater reduction in absolute and fractional reabsorption of Na+, Cl-, and K+ up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na+/glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.

Role of FGF21 and GCN2 in mediating the metabolic response to dietary protein restriction

2016 ◽  
Vol 11 (S 01) ◽  
Author(s):  
T Laeger ◽  
DC Albarado ◽  
L Trosclair ◽  
J Hedgepeth ◽  
CD Morrison
Keyword(s):  
Dietary Protein ◽  
Metabolic Response ◽  
Protein Restriction ◽  
Dietary Protein Restriction

Neuronal FGF-21 Signaling–A Sensor of Dietary Protein Restriction

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 261-LB
Author(s):  
CRISTAL M. HILL ◽  
MADELEINE V. DEHNER ◽  
DAVID MCDOUGAL ◽  
HANS-RUDOLF BERTHOUD ◽  
HEIKE MUENZBERG ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Protein Restriction ◽  
Dietary Protein Restriction

238-LB: Dietary Protein Restriction Induces Myocardial Dysfunction Despite Reducing Body Weight in Aged C57BL/6J Mice

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 238-LB
Author(s):  
CHRISTOPHER L. AXELROD ◽  
WAGNER S. DANTAS ◽  
GANGARAO DAVULURI ◽  
WILLIAM T. KING ◽  
CRISTAL M. HILL ◽  
...  
Keyword(s):  
Body Weight ◽  
Dietary Protein ◽  
Myocardial Dysfunction ◽  
Protein Restriction ◽  
Dietary Protein Restriction

scholarly journals The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2609
Author(s):  
Han Fang ◽  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Laura A. Forney ◽  
Thomas W. Gettys
Keyword(s):  
Amino Acids ◽  
Dietary Protein ◽  
Target Genes ◽  
Protein Restriction ◽  
Metabolic Phenotype ◽  
Sulfur Amino Acids ◽  
Transcriptional Responses ◽  
Similar Reduction ◽  
Dietary Protein Restriction ◽  
Methionine Restriction

Dietary protein restriction and dietary methionine restriction (MR) produce a comparable series of behavioral, physiological, biochemical, and transcriptional responses. Both dietary regimens produce a similar reduction in intake of sulfur amino acids (e.g., methionine and cystine), and both diets increase expression and release of hepatic FGF21. Given that FGF21 is an essential mediator of the metabolic phenotype produced by both diets, an important unresolved question is whether dietary protein restriction represents de facto methionine restriction. Using diets formulated from either casein or soy protein with matched reductions in sulfur amino acids, we compared the ability of the respective diets to recapitulate the metabolic phenotype produced by methionine restriction using elemental diets. Although the soy-based control diets supported faster growth compared to casein-based control diets, casein-based protein restriction and soy-based protein restriction produced comparable reductions in body weight and fat deposition, and similar increases in energy intake, energy expenditure, and water intake. In addition, the prototypical effects of dietary MR on hepatic and adipose tissue target genes were similarly regulated by casein- and soy-based protein restriction. The present findings support the feasibility of using restricted intake of diets from various protein sources to produce therapeutically effective implementation of dietary methionine restriction.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

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