The altered renal and hepatic expression of solute carrier transporters (SLCs) in type 1 diabetic mice

PLoS One. 2015 Mar 19;10(3):e0120760. doi: 10.1371/journal.pone.0120760. eCollection 2015.

Abstract

Diabetes mellitus is a chronic metabolic disorder that significantly affects human health and well-being. The Solute carrier transporters (SLCs), particularly the Organic anion/cation transporters (Oats/Octs/Octns), Organic anion transporting polypeptides (Oatps) and Oligopeptide transporters (Pepts) are essential membrane proteins responsible for cellular uptake of many endogenous and exogenous substances such as clinically important drugs. They are widely expressed in mammalian key organs especially the kidney and liver, in which they facilitate the influx of various drug molecules, thereby determining their distribution and elimination in body. The altered expression of SLCs in diabetes mellitus could have a profound and clinically significant influence on drug therapies. In this study, we extensively investigated the renal and hepatic expression of twenty essential SLCs in the type 1 diabetic Ins2Akita murine model that develops both hyperglycemia and diabetes-related complications using real-time PCR and immunoblotting analysis. We found that the renal expression of mOatp1a1, mOatp1a6, mOat1, mOat3, mOat5, mOct2 and mPept2 was decreased; while that of mPept1 was increased at the mRNA level in the diabetic mice compared with non-diabetic controls. We found up-regulated mRNA expression of mOatp1a4, mOatp1c1, mOctn2, mOct3 and mPept1 as well as down-regulation of mOatp1a1 in the livers of diabetic mice. We confirmed the altered protein expression of several SLCs in diabetic mice, especially the decreased renal and hepatic expression of mOatp1a1. We also found down-regulated protein expression of mOat3 and mOctn1 in the kidneys as well as increased protein expression of mOatp1a4 and mOct3 in the livers of diabetic mice. Our findings contribute to better understanding the modulation of SLC transporters in type 1 diabetes mellitus, which is likely to affect the pharmacokinetic performance of drugs that are transported by these transporters and therefore, forms the basis of future therapeutic optimization of regimens in patients with type 1 diabetes mellitus.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Down-Regulation
  • Female
  • Immunoblotting
  • Kidney / metabolism*
  • Liver / metabolism*
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Peptide Transporter 1
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Symporters / genetics
  • Symporters / metabolism
  • Up-Regulation

Substances

  • Membrane Transport Proteins
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • Peptide Transporter 1
  • RNA, Messenger
  • Slc15a1 protein, mouse
  • Symporters

Grants and funding

The authors have no support or funding to report.