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Type 1 diabetes mellitus induces structural changes and molecular remodelling in the rat kidney

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Abstract

There is much evidence that diabetes mellitus (DM)-induced hyperglycemia (HG) is responsible for kidney failure or nephropathy leading to cardiovascular complications. Cellular and molecular mechanism(s) whereby DM can damage the kidney is still not fully understood. This study investigated the effect of streptozotocin (STZ)-induced diabetes (T1DM) on the structure and associated molecular alterations of the isolated rat left kidney following 2 and 4 months of the disorder compared to the respective age-matched controls. The results revealed hypertrophy and general disorganized architecture of the kidney characterized by expansion in glomerular borders, tubular atrophy and increased vacuolization of renal tubular epithelial cells in the diabetic groups compared to controls. Electron microscopic analysis revealed ultrastructural alterations in the left kidney highlighted by an increase in glomerular basement membrane width. In addition, increased caspase-3 immunoreactivity was observed in the kidney of T1DM animals compared to age-matched controls. These structural changes were associated with elevated extracellular matrix (ECM) deposition and consequently, altered gene expression profile of ECM key components, together with elevated levels of key mediators (MMP9, integrin 5α, TIMP4, CTGF, vimentin) and reduced expressions of Cx43 and MMP2 of the ECM. Marked hypertrophy of the kidney was highlighted by increased atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. These changes also correlated with increased TGFβ1 activity, gene expression in the left kidney and elevated active TGFβ1 in the plasma of T1DM rats compared to control. The results clearly demonstrated that TIDM could elicit severe structural changes and alteration in biochemical markers (remodelling) in the kidney leading to diabetic nephropathy (DN).

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Authors and Affiliations

  1. School of Forensic and Applied Sciences, University of Central Lancashire, Preston, England, PR1 2HE, UK

    Raphael M. Singh, Jaipaul Singh & Tehreem Waqar

  2. Faculty of Medicine and Health Sciences, University of Guyana, Turkeyen, Georgetown, Guyana

    Raphael M. Singh

  3. Department of Physiology and College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates

    Frank C. Howarth

  4. Department of Human Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates

    Ernest Adeghate

  5. Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Centre, Omaha, NE, 68198, USA

    Keshore Bidasee

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  1. Raphael M. Singh
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Correspondence to Raphael M. Singh.

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Singh, R.M., Howarth, F.C., Adeghate, E. et al. Type 1 diabetes mellitus induces structural changes and molecular remodelling in the rat kidney. Mol Cell Biochem 449, 9–25 (2018). https://doi.org/10.1007/s11010-018-3338-4

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