Effect of mild hypoinsulinemia on renal hypertrophy: growth hormone/insulin-like growth factor I system in mild streptozotocin diabetes.
The metabolic aberrations associated with diabetes mellitus profoundly alter the growth hormone/insulin-like growth factor I (GH/IGF-I) system. In severe experimental diabetes, serum IGF-I level is reduced, reflecting altered hepatic expression. On the other hand, increased levels of kidney IGF-I have been implicated in the development of diabetic kidney disease. This study aimed to examine the effect of mild experimental diabetes with hypoinsulinemia on both the systemic and renal GH/IGF-I systems in a low-dose streptozotocin (STZ)-induced diabetic rat. Diabetic animals with mild hypoinsulinemia developed renal hyperfiltration within 3 days of diabetes, whereas the renal size increased significantly only between 30 and 48 days of diabetes. Plasma GH levels were unchanged during the entire course of the study, but a decrease in serum IGF-I, IGF-binding protein 3 (IGFBP-3), and IGF-binding protein 4 (IGFBP-4) occurred after 10, 30, and 48 days. Kidney IGF-I and IGF-binding protein 1 (IGFBP-1) mRNA expression increased after 10 and 30 days of diabetes. A significant increase in kidney IGFBP-1/2, IGFBP-3, and IGFBP-4 proteins was seen after 48 days of diabetes. A positive correlations was found between renal growth and insulin/glucose ratio (r=.57), kidney IGF-I (r=.57), IGFBP-1 mRNA (r=.43), IGFBP-1/2 (r=.41), and IGFBP-4 levels (r=.40). These results demonstrate hyperfiltration within 3 days of diabetes and a similar response in the IGF-I system in mildly and severely hypoinsulinemic rats; however, renomegaly develops slower in mildly diabetic rats at least partly due to delayed changes in the renal IGF and IGF BPs.
Khamaisi
Mogher
M
Diabetes Center and Department of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel. murir@hadassah.org.il
Flyvbjerg
Allan
A
Haramati
Ziv
Z
Raz
Gadi
G
Wexler
Isaiah D
ID
Raz
Itamar
I
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000473:pathology; D005215:Fasting; D013006:Growth Hormone / Q000097:blood*; D007328:Insulin / Q000097:blood* / Q000172:deficiency; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D007668:Kidney / Q000033:anatomy & histology / Q000473:pathology*; D008297:Male; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012044:Regression Analysis
D001786:Blood Glucose; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D013006:Growth Hormone