Astragaloside IV prevents kidney injury caused by iatrogenic hyperinsulinemia in a streptozotocininduced diabetic rat model.
Int J Mol Med
; 41(2): 1078-1088, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-29207011
ABSTRACT
Diabetic patients are able to manage their blood glucose with exogenous insulin but, ultimately, remain at risk of diabetic nephropathy (DN). Longterm use of insulin may lead to iatrogenic hyperinsulinemia, which has been suggested to cause kidney injury. However, there are no effective interventions for iatrogenic hyperinsulinemia leading to kidney damage. In the present paper, the hypothesis that astragaloside IV (ASIV), a novel saponin purified from Astragalus membranaceus (Fisch) Bunge, may prevent DN in iatrogenic hyperinsulinemic diabetic rats through antioxidative and antiinflammatory mechanisms was investigated. Diabetes was induced with streptozotocin (STZ) (55 mg/kg) by intraperitoneal injection in rats. At 1 week following STZ injection, the diabetic rats were treated with Levemir subcutaneously for 4 weeks. Diabetic rat insulin levels >30 µU/ml were considered as iatrogenic hyperinsulinemia. Rats were divided into six groups (n=8 per group) Iatrogenic hyperinsulinemic rats, and iatrogenic hyperinsulinemic rats treated with Tempol and ASIV at 2.5, 5 and 10 mg/kg/day, intragastric infusion, for 12 weeks. The normal rats were used as a nondiabetic control group. ASIV ameliorated albuminuria, mesangial cell proliferation, basement membrane thickening and podocyte foot process effacement in iatrogenic hyperinsulinemic rats. In iatrogenic hyperinsulinemic rat renal tissues, malondialdehyde, interleukin1ß (IL1ß), tumor necrosis factorα (TNFα), type IV collagen and laminin levels were increased, whereas glutathione peroxidase and superoxide dismutase activity levels were decreased. Nicotinamide adenine dinucleotide phosphate oxidase 4 expression and extracellular signalregulated kinase 1/2 (ERK1/2) activation were upregulated, and canonical transient receptor potential cation channel 6 (TRPC6) protein expression was downregulated. However, all these abnormalities were attenuated by ASIV. These findings suggested that ASIV prevented rat kidney injury caused by iatrogenic hyperinsulinemia by inhibiting oxidative stress, IL1ß and TNFα overproduction, downregulating ERK1/2 activation, and upregulating TRPC6 expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
/
Triterpenos
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Diabetes Mellitus Experimental
/
Injúria Renal Aguda
/
Hiperinsulinismo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2018
Tipo de documento:
Article