scholarly journals Erratum to “Meprin Metalloprotease Deficiency Associated with Higher Mortality Rates and More Severe Diabetic Kidney Injury in Mice with STZ-Induced Type 1 Diabetes”

2018 ◽  
Vol 2018 ◽  
pp. 1-1
Author(s):  
John E. Bylander ◽  
Faihaa Ahmed ◽  
Sabena M. Conley ◽  
Jean-Marie Mwiza ◽  
Elimelda Moige
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Injury ◽  
Mortality Rates ◽  
Diabetic Kidney

scholarly journals LC-MS-based metabolomics analysis to identify meprin-β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury

2019 ◽  
Vol 317 (4) ◽  
pp. F1034-F1046 ◽  
Author(s):  
Jessica Gooding ◽  
Lei Cao ◽  
Faihaa Ahmed ◽  
Jean-Marie Mwiza ◽  
Mizpha Fernander ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Liquid Chromatography ◽  
Kidney Injury ◽  
Variable Importance ◽  
Proteolytic Processing ◽  
Indoxyl Sulfate ◽  
Pima Indians ◽  
Diabetic Kidney ◽  
Metabolomics Analysis

Meprin metalloproteases have been implicated in the pathophysiology of diabetic kidney disease (DKD). Single-nucleotide polymorphisms in the meprin-β gene have been associated with DKD in Pima Indians, a Native American ethnic group with an extremely high prevalence of DKD. In African American men with diabetes, urinary meprin excretion positively correlated with the severity of kidney injury. In mice, meprin activity decreased at the onset of diabetic kidney injury. Several studies have identified meprin targets in the kidney. However, it is not known how proteolytic processing of the targets by meprins impacts the metabolite milieu in kidneys. In the present study, global metabolomics analysis identified differentiating metabolites in kidney tissues from wild-type and meprin-β knockout mice with streptozotocin (STZ)-induced type 1 diabetes. Kidney tissues were harvested at 8 wk post-STZ and analyzed by hydrophilic interaction liquid chromatography ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Principal component analysis identified >200 peaks associated with diabetes. Meprin expression-associated metabolites with strong variable importance of projection scores were indoxyl sulfate, N-γ-l-glutamyl-l-aspartic acid, N-methyl-4-pyridone-3-carboxamide, inosine, and cis-5-decenedioic acid. N-methyl-4-pyridone-3-carboxamide has been previously implicated in kidney injury, and its isomers, 4-PY and 2-PY, are markers of peroxisome proliferation and inflammation that correlate with creatinine clearance and glucose tolerance. Meprin deficiency-associated differentiating metabolites with high variable importance of projection scores were cortisol, hydroxymethoxyphenylcarboxylic acid- O-sulfate, and isovaleryalanine. The data suggest that meprin-β activity enhances diabetic kidney injury in part by altering the metabolite balance in kidneys, favoring high levels of uremic toxins such as indoxyl sulfate and N-methyl-pyridone-carboxamide.

scholarly journals Meprin Metalloprotease Deficiency Associated with Higher Mortality Rates and More Severe Diabetic Kidney Injury in Mice with STZ-Induced Type 1 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
John E. Bylander ◽  
Faihaa Ahmed ◽  
Sabena M. Conley ◽  
Jean-Marie Mwiza ◽  
Elimelda Moige Ongeri
Keyword(s):  
Type 1 Diabetes ◽  
Survival Rates ◽  
Kidney Injury ◽  
Diabetic Kidney ◽  
Nitrogen Levels ◽  
Protein Levels ◽  
Urine Albumin ◽  
Membrane Bound

Meprins are membrane-bound and secreted metalloproteinases consisting of α and/or β subunits that are highly expressed in kidney epithelial cells and are differentially expressed in podocytes and leukocytes (macrophages and monocytes). Several studies have implicated meprins in the progression of diabetic nephropathy (DN) and fibrosis-associated kidney disease. However, the mechanisms by which meprins modulate DN are not understood. To delineate the role of meprins in DN, we subjected meprin αβ knockout (αβKO) mice and their wild-type (WT) counterparts to streptozotocin-induced type 1 diabetes. The 18-week survival rates were significantly lower for diabetic meprin αβKO mice when compared to those for their WT counterparts. There were significant decreases in mRNA and protein levels for both meprin α and β in diabetic WT kidneys. Furthermore, the blood urea nitrogen levels and urine albumin/creatinine ratios increased in diabetic meprin αβKO but not in diabetic WT mice, indicating that meprins may be protective against diabetic kidney injury. The brush border membrane levels of villin, a meprin target, significantly decreased in diabetic WT but not in diabetic meprin αβKO kidneys. In contrast, isoform-specific increases in cytosolic levels of the catalytic subunit of PKA, another meprin target, were demonstrated for both WT and meprin αβKO kidneys.

scholarly journals HLA class II is a factor in cardiovascular morbidity and mortality rates in patients with type 1 diabetes

Diabetologia ◽  
2012 ◽  
Vol 55 (11) ◽  
pp. 2963-2969 ◽  
Author(s):  
J. Söderlund ◽  
◽  
C. Forsblom ◽  
J. Ilonen ◽  
L. M. Thorn ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mortality Rates ◽  
Class Ii ◽  
Hla Class Ii ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Cardiovascular Morbidity And Mortality

scholarly journals C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes

Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2713-2723 ◽  
Author(s):  
F. Liu ◽  
H. Y. Chen ◽  
X. R. Huang ◽  
A. C. K. Chung ◽  
L. Zhou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
C Reactive Protein ◽  
Diabetic Kidney ◽  
Reactive Protein

scholarly journals Urine inositol pentakisphosphate 2-kinase and changes in kidney structure in early diabetic kidney disease in type 1 diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. F1484-F1492
Author(s):  
Helen C. Looker ◽  
Michael L. Merchant ◽  
Madhavi J. Rane ◽  
Robert G. Nelson ◽  
Paul L. Kimmel ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Albumin Excretion Rate ◽  
Diabetes Duration ◽  
Limit Of Quantification ◽  
Diabetic Kidney ◽  
Kidney Structure

We examined the association of urine inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPP2K) with the presence and progression of diabetic kidney disease (DKD) lesions. Urine IPP2K was measured at baseline by quantitative liquid chromatography-mass spectrometry in 215 participants from the Renin-Angiotensin System Study who had type 1 diabetes and were normoalbuminuric and normotensive with normal or increased glomerular filtration rate (GFR). Urine IPP2K was detectable in 166 participants. Participants with IPP2K below the limit of quantification (LOQ) were assigned concentrations of LOQ/√2. All concentrations were then standardized to urine creatinine (Cr) concentration. Kidney morphometric data were available from biopsies at baseline and after 5 yr. Relationships of IPP2K/Cr with morphometric variables were assessed by linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, treatment assignment, and, for longitudinal analyses, baseline structure. Baseline mean age was 29.7 yr, mean diabetes duration 11.2 yr, median albumin excretion rate 5.0 μg/min, and mean iohexol GFR 129 ml·min−1·1.73m−2. Higher IPP2K/Cr was associated with higher baseline peripheral glomerular total filtration surface density [Sv(PGBM/glom), tertile 3 vs. tertile 1 β = 0.527, P = 0.011] and with greater preservation of Sv(PGBM/glom) after 5 yr ( tertile 3 vs. tertile 1 β = 0.317, P = 0.013). Smaller increases in mesangial fractional volume ( tertile 3 vs. tertile 1 β = −0.578, P = 0.018) were observed after 5 yr in men with higher urine IPP2K/Cr concentrations. Higher urine IPP2K/Cr is associated with less severe kidney lesions at baseline and with preservation of kidney structure over 5 yr in individuals with type 1 diabetes and no clinical evidence of DKD at baseline.

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