Neonatal streptozotocin-induced glucose intolerance: different consequences in Lyon normotensive and hypertensive rats.
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.


OBJECTIVE
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.
Emonnot
Léa
L
Département de Physiologie et Pharmacologie Clinique - EA3995, Université Lyon 1, France.
Cohen
Richard
R
Lo
Ming
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000503:physiopathology*; D006029:Glycosuria; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology; D008297:Male; D011141:Polyuria / Q000139:chemically induced; D011507:Proteinuria / Q000209:etiology*; D051381:Rats; D011918:Rats, Inbred SHR
D001786:Blood Glucose