TY  - JOUR
A1  - Raila, Jens
A1  - Schweigert, Florian J.
A1  - Kohn, Barbara
T1  - Relationship between urinary Tamm-Horsfall protein excretion and renal function in dogs with naturally occurring renal disease
JF  - Veterinary clinical pathology
N2  - Background Tamm-Horsfall protein (THP) is physiologically excreted in urine, but little is known about the role of THP in the diagnosis of renal disease in dogs. Objective The aim of this study was to evaluate to which extent naturally occurring renal disease affects the urinary excretion of THP. Methods Dogs were divided into 5 groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-ClCr) rates: Group A (healthy control dogs; n=8), nonazotemic and nonproteinuric dogs, with P-ClCr rates > 90mL/min/m2; group B (n=25), nonazotemic and nonproteinuric dogs with reduced P-ClCr rates (51-89mL/min/m2); group C (n=7), nonazotemic but proteinuric dogs with P-ClCr rates 53-98mL/min/m2; group D (n=8), azotemic and borderline proteinuric dogs (P-ClCr rates: 22-45mL/min/m2); and group E (n=15), azotemic and proteinuric dogs (not tested for P-ClCr). THP was measured by quantitative Western blot analysis, and the ratio of THP-to-urinary creatinine (THP/UC) was calculated. Results The THP/UC concentrations were not different among dogs of groups A-D, but were reduced in dogs of group E (P<.001). THP/UC correlated negatively with serum creatinine (P<.01) and UP/UC (P<.01), but was not significantly associated with P-ClCr. Conclusions Decreased levels of THP/UC were present in moderately to severely azotemic and proteinuric dogs. This suggests tubular injury in these dogs and that THP might be useful as urinary marker to study the pathogenesis of renal disease.
KW  - Distal tubules
KW  - dog
KW  - kidney
KW  - lower nephron
KW  - proteinuria
KW  - urine
Y1  - 2014
U6  - https://doi.org/10.1111/vcp.12143
SN  - 0275-6382
SN  - 1939-165X
VL  - 43
IS  - 2
SP  - 261
EP  - 265
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Nair, Anil V.
A1  - Hocher, Berthold
A1  - Verkaart, Sjoerd
A1  - van Zeeland, Femke
A1  - Pfab, Thiemo
A1  - Slowinski, Torsten
A1  - Chen, You-Peng
A1  - Schlingmann, Karl Peter
A1  - Schaller, Andre
A1  - Gallati, Sabina
A1  - Bindels, Rene J.
A1  - Konrad, Martin
A1  - Hönderop, Joost G.
T1  - Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 ((VI)-I-1393, (KE)-E-1584) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6 ((VI)-I-1393) and TRPM6((KE)-E-1584), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T-1391) and TRPM6(S-1583). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.
KW  - kidney
KW  - distal convoluted tubule
KW  - transient receptor potential
KW  - vesicular trafficking
Y1  - 2012
U6  - https://doi.org/10.1073/pnas.1113811109
SN  - 0027-8424
VL  - 109
IS  - 28
SP  - 11324
EP  - 11329
PB  - National Acad. of Sciences
CY  - Washington
ER  -