Diabetes Metab J.  2018 Aug;42(4):338-342. 10.4093/dmj.2017.0095.

Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea. pts@jbnu.ac.kr

Abstract

The effect of sodium-glucose cotransporter 2 inhibitors on peripheral nerves and kidneys in diabetes mellitus (DM) remains unexplored. Therefore, this study aimed to explore the effect of empagliflozin in diabetic rats. DM in rats was induced by streptozotocin injection, and diabetic rats were treated with empagliflozin 3 or 10 mg/kg. Following 24-week treatment, response thresholds to four different stimuli were tested and found to be lower in diabetic rats than in normal rats. Empagliflozin significantly prevented hypersensitivity (P < 0.05) and the loss of skin intraepidermal nerve fibers, and mesangial matrix expansion in diabetic rats. Results of this study demonstrate the potential therapeutic effects of empagliflozin for the treatment of diabetic peripheral neuropathy and nephropathy.

Keyword

Diabetes mellitus, experimental; Diabetic nephropathies; Diabetic neuropathies; Peripheral nerves; Sodium-glucose transporter 2

MeSH Terms

Animals
Diabetes Mellitus
Diabetes Mellitus, Experimental
Diabetic Nephropathies
Diabetic Neuropathies
Hypersensitivity
Kidney*
Nerve Fibers
Peripheral Nerves*
Peripheral Nervous System Diseases
Rats*
Skin
Sodium-Glucose Transporter 2
Streptozocin
Therapeutic Uses
Sodium-Glucose Transporter 2
Streptozocin
Therapeutic Uses

Figure

  • Fig. 1 Intraepidermal nerve fiber density and protein gene product (PGP) 9.5-positive small nerve fibers in the dorsum of nondiabetic and diabetic rats treated with or without empagliflozin. PGP-9.5 immunoreactive small nerve fibers were markedly decreased in the diabetes mellitus (DM) group. However, nerve fiber loss was significantly prevented in the empagliflozin-treated DM groups compared to the untreated DM group. Horizontal bar indicates 100 µm. NOR, normal plus vehicle treated group; IENFD, intraepidernal nerve fiber density. aP<0.05 vs. NOR, bP<0.05 vs. DM.

  • Fig. 2 Protein gene product (PGP) 9.5-positive small nerve fibers in the renal cortex and periodic acid-Schiff staining of kidney tissue sections. (A) Numerous PGP-9.5-stained small nerve fibers were observed in the empagliflozin-treated groups compared to the diabetes mellitus (DM) group. (B) The PAS-positive glomerular mesangial area was expanded in the DM group compared to the normal plus vehicle treated group. These changes were significantly ameliorated in the DM+E10 group; however, the effect was not significant in the DM+E3 group. Horizontal bar indicates 50 µm. DM+E3 and DM+E10, diabetes mellitus plus empagliflozin at 3 and 10 mg/kg, respectively.


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