ISSN: 2251-8363    eISSN: 2251-8819  
J Nephropathol. 2018;7(3):171-181.
doi:10.15171/jnp.2018.37

Original Article

Metformin with insulin relieves oxidative stress and confers renoprotection in type 1 diabetes in vivo

Christine Driver, Julia Achieng Hayangah, Ntsoaki Annah Nyane, Peter Mark Oroma Owira *

1 Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal P.O. Box X5401, Durban, South Africa
*Corresponding author: Peter Mark Oroma Owira, Email: owirap@ukzn.ac.za

Abstract

Background: Oxidative stress and impaired antioxidant capacity in diabetes are associated with diabetic nephropathy. Metformin, as an adjunct to insulin could decrease oxidative stress and may therefore improve renal function in type 1 diabetes (T1D).

Objectives: To investigate the effects of metformin as adds-on therapy to insulin on renal dysfunction in T1D.

Materials and Methods: Male Sprague-Dawley rats (230-250 g) were divided into 5 groups (n =7). Rats in groups A and B were orally treated with 3.0 mL/kg body weight (BW) of distilled water, while those in groups C and D were treated with insulin (4.0 U/kg BW bid) or oral metformin (250 mg/kg BW), respectively. Group E rats were similarly treated with both metformin and insulin. Groups B-E were rendered diabetic by intraperitoneal injections of 65 mg/kg BW of streptozotocin. Fasting blood glucose concentrations and glucose tolerance tests were done. The animals were sacrificed by halothane overdose after 56 days, blood taken by cardiac puncture and kidneys excised and stored at -80°C for further analysis.

Results: Untreated diabetic rats exhibited significant weight loss, increased polydipsia and polyuria, impaired glucose tolerance, electrolyte retention, reduced creatinine clearance and urea excretion and increased oxidative stress compared to controls, respectively. However, these were reversed by treatment with metformin and insulin.

Conclusions: Metformin does not improve glycemic control in TID but exerts renoprotective effects by reducing oxidative stress in the presence of insulin. Metformin should therefore be considered for adjunct therapy with insulin in TID.

Implication for health policy/practice/research/medical education:

Although metformin is known to exert no hypoglycemic effects in type 1 diabetes, our findings here suggest that it may mitigate the development of diabetic nephropathy by its anti-oxidant effects. Metformin should therefore be considered as adjunct therapy to insulin in type 1 diabetes.

Please cite this paper as: Driver C, Hayangah JA, Nyane NA, Owira PMO. Metformin with insulin relieves oxidative stress and confers renoprotection in type 1 diabetes in vivo. J Nephropathol. 2018;7(3):171-181. DOI: 10.15171/jnp.2018.37.

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Submitted: 07 Dec 2016

Accepted: 18 Apr 2017
First published online: 09 May 2017
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