Léa Emonnot1, Richard Cohen, Ming Lo. 1. Département de Physiologie et Pharmacologie Clinique - EA3995, Université Lyon 1, France.
Abstract
BACKGROUND: Lyon hypertensive (LH) rats exhibit a mild hypertension associated with excessive body weight, spontaneous hyperlipidemia, elevated insulin/glucose ratio and exaggerated urinary protein excretion. AIMS: We aimed to develop, in LH rats and their normotensive control (LL) rats, a moderate non-insulin-dependent diabetic model to study the different consequences on metabolic and renal functions. METHODS: Non-insulin-dependent diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at 2 days of age (50, 75 or 100 mg/kg for LH and 75, 100 or 125 mg/kg for LL rats). The evolution, with age, of glycemia, glucose tolerance (glucose 2 g/kg by gavage), blood pressure, plasma lipids and urinary protein and albumin excretions were studied in control and STZ-treated LH and LL rats. RESULTS: Although fasting glycemia was not significantly changed, the neonatal administration of STZ increased non-fasting glycemia and induced a marked glucose intolerance that were comparable between LH rats receiving 75 mg/kg and LL rats receiving 100 mg/kg of STZ. Interestingly, in treated LH rats only, the impaired glucose tolerance was accompanied by further metabolic and renal dysfunctions characterized by additional increases in plasma cholesterol (+28%) and triglycerides (+105%) and accelerated progression of proteinuria (+36%) and albuminuria (+48%). CONCLUSIONS: These observations indicate that susceptibility to diabetic metabolic disorders and renal diseases may be linked to the genetic predisposition to hypertension. This new model offers a reasonable reflection of the human situation, where hypertension and non-insulin-dependent diabetes often coincide, suitable for molecular, biochemical and pharmacological investigations.
BACKGROUND: Lyon hypertensive (LH) rats exhibit a mild hypertension associated with excessive body weight, spontaneous hyperlipidemia, elevated insulin/glucose ratio and exaggerated urinary protein excretion. AIMS: We aimed to develop, in LHrats and their normotensive control (LL) rats, a moderate non-insulin-dependent diabetic model to study the different consequences on metabolic and renal functions. METHODS:Non-insulin-dependent diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at 2 days of age (50, 75 or 100 mg/kg for LH and 75, 100 or 125 mg/kg for LL rats). The evolution, with age, of glycemia, glucose tolerance (glucose 2 g/kg by gavage), blood pressure, plasma lipids and urinary protein and albumin excretions were studied in control and STZ-treated LH and LL rats. RESULTS: Although fasting glycemia was not significantly changed, the neonatal administration of STZ increased non-fasting glycemia and induced a marked glucose intolerance that were comparable between LHrats receiving 75 mg/kg and LL rats receiving 100 mg/kg of STZ. Interestingly, in treated LHrats only, the impaired glucose tolerance was accompanied by further metabolic and renal dysfunctions characterized by additional increases in plasma cholesterol (+28%) and triglycerides (+105%) and accelerated progression of proteinuria (+36%) and albuminuria (+48%). CONCLUSIONS: These observations indicate that susceptibility to diabetic metabolic disorders and renal diseases may be linked to the genetic predisposition to hypertension. This new model offers a reasonable reflection of the human situation, where hypertension and non-insulin-dependent diabetes often coincide, suitable for molecular, biochemical and pharmacological investigations.