Metformin does not prevent glucose intolerance but improves renal function and reduces oxidative stress in type 1 diabetes.
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Date
2016
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Abstract
Type 1 diabetes (T1D) is a chronic condition caused by the complete destruction of insulin
producing pancreatic β-cells. Increased oxidative stress and impaired antioxidant capacity are
associated with the development of diabetic complications such as diabetic nephropathy.
Metformin, a drug commonly used in the treatment of type 2 diabetes, has been suggested to
have antioxidant capacity. We hypothesise that metformin, when used as an adjunct to insulin
in T1D may help prevent the development of diabetic nephropathy by decreasing oxidative
stress.
Sprague-Dawley rats (230-250g) were divided into 5 groups, (Group A: untreated controls,
B: diabetic control, C: T1D + insulin (4U/kg twice daily), D: T1D + metformin (250mg/kg
via oral gavage), E: T1D + metformin + insulin). Diabetes was induced in groups B-E by
intraperitoneal streptozotocin injection at a dose of 65mg/kg body weight and diabetes was
confirmed 48 hours later. Glucose tolerance test, serum and urinary electrolytes (K+,Cl-
,Na+), creatinine, urea, superoxide dismutase activity, glutathione concentration and
malondialdehyde concentration were analysed.
Metformin alone did not improve glucose intolerance. Both the diabetic control group as well
as the group treated with metformin alone experienced hyperglycemia, polydipsia, polyuria,
weight loss and impaired glucose tolerance. However, when metformin was added to insulin
there was a significant increase in electrolyte excretion and also greatly improved creatinine
clearance when compared to the diabetic control group. Metformin with insulin further
reduced superoxide dismutase activity compared to the diabetic control, increased glutathione
concentration as well as reduced malondialdehyde concentrations in both plasma and renal
tissue. In conclusion, metformin has positive additive effects on oxidative stress and renal
function when used as an adjunct therapy to insulin for T1D.
Description
Master of Science in Pharmaceutical Sciences. University of KwaZulu-Natal, Durban 2016.
Keywords
Metformin., Diabetes - research - South Africa., Diabetes - treatment., Insulin resistance., Renal pharmacology.