Abstract：
BACKGROUND/AIMS:The contribution of preexisting hypercholesterolemia to diabetic nephropathy remains unclear. We assessed the impact of hypercholesterolemia on diabetic nephropathy using a double knockout (DKO) mouse, null for the low-density lipoprotein receptor (LDLRNDASH;/NDASH;) and the apoB mRNA editing catalytic polypeptide 1 (APOBEC1NDASH;/NDASH;). METHODS:Wild-type (WT) and DKO mice received sham or streptozotocin injections at age 7 weeks, yielding control (WT-C, DKO-C) and diabetic (WT-D, DKO-D) groups. At sacrifice (age 40 weeks), albuminuria was determined by ELISA, and kidney sections were examined by light and electron microscopy. RESULTS:Albuminuria increased in diabetic mice (WT-D: 82.4 +/- 37.2 microg/18 h; DKO-D: 58.0 +/- 45.7 microg/18 h) versusnondiabetic controls (WT-C: 10.2 +/- 7.2 microg/18 h; DKO-C: 8.6 +/- 5.3 microg/18 h) (p LT; 0.0001), but was unaffected by hypercholesterolemia. Light microscopy of kidney sections demonstrated increased collagen levels in glomeruli in WT-D mice, but not in DKO-D mice or either control group. Electron microscopy showed a thickened glomerular basement membrane in WT-D mice only. The proximal tubular basement membrane thickness was increased in both diabetic groups versusnondiabetic controls (p LT; 0.01); in WT-D mice this was attributable to collagen accumulation, but in DKO-D mice it was mainly caused by lipid vacuoles. CONCLUSIONS:In this animal model, preexisting hypercholesterolemia did not exacerbate either glomerular lesions of diabetes (collagen accumulation, basement membrane thickening) or albuminuria, but appeared to mitigate these effects. Furthermore, the combination of hypercholesterolemia and diabetes resulted in a significant lipid accumulation in the tubular basement membrane.
journal_name
Kidney Blood Press Resjournal_title
Kidney & blood pressure researchauthors
Hammad SM,Hazen-Martin DJ,Sohn M,Eldridge L,Powell-Braxton L,Won W,Lyons TJdoi
10.1159/000073942keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
351-61issue
5-6eissn
1420-4096issn
1423-0143pii
73942journal_volume
26pub_type
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journal_title：Kidney & blood pressure research
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abstract：:Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells ...
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abstract：INTRODUCTION:Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and is considered to be a sterile inflammatory disease. Increasing evidence suggest that pyroptosis and subsequent inflammatory response play a key role in the pathogenesis of DN. However, the underlying cellular and molecular mechani...
journal_title：Kidney & blood pressure research
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journal_title：Kidney & blood pressure research
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更新日期：1996-01-01 00:00:00
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journal_title：Kidney & blood pressure research
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更新日期：2012-01-01 00:00:00
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doi：10.1159/000104818
更新日期：2007-01-01 00:00:00
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doi：10.1159/000483023
更新日期：2017-01-01 00:00:00
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abstract：:The present investigation examined the possible influence of urinary calcium excretion on the concentration of renal calbindin-D28k. Thiazide diuretics stimulate calcium transport across the epithelial cells of the distal tubule, which express calbindin-D28k in high concentrations. Calbindin-D28k is assumed to facilit...
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doi：10.1159/000174153
更新日期：1997-01-01 00:00:00
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journal_title：Kidney & blood pressure research
pub_type： 杂志文章
doi：10.1159/000317943
更新日期：2010-01-01 00:00:00
abstract：:The aim of this study was to investigate whether the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One grou...
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doi：10.1159/000025890
更新日期：1998-01-01 00:00:00
abstract：BACKGROUND/AIMS:Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI). The aim of the present study was to evaluate the protective effect of GSK-3β inhibition (TDZD-8) on I/R-induced renal injury through the Nrf2/HO-1 pathway in a streptozocin (STZ)-induced diabetic rat model. METHODS:STZ-in...
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doi：10.1159/000477947
更新日期：2017-01-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2005-01-01 00:00:00
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更新日期：2015-01-01 00:00:00
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更新日期：2020-01-01 00:00:00
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更新日期：2014-01-01 00:00:00
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更新日期：2016-01-01 00:00:00
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更新日期：2018-01-01 00:00:00
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journal_title：Kidney & blood pressure research
pub_type： 杂志文章
doi：10.1159/000443429
更新日期：2016-01-01 00:00:00
abstract：:Backgroud/Aims: The aim of this study was to investigate the potential renoprotective effect of rapamycin on the autophagy of podocytes treated with the supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from immunoglobulin A nephropathy (IgAN) patients. METHODS:Monomeric IgA1 (mIgA1) was isolated f...
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doi：10.1159/000475484
更新日期：2017-01-01 00:00:00
abstract：:Inhibitors of angiotensin-converting enzyme (ACE) or beta isoforms of protein kinase C (PKC) are nephroprotective in diabetes mellitus. We investigated the influence of streptozotocin (STZ)-induced diabetes mellitus and of treatment with the ACE inhibitor lisinopril (4 mg/kg p.o. twice daily for 4 weeks) on the expres...
journal_title：Kidney & blood pressure research
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更新日期：2002-01-01 00:00:00
