Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys obesus (sand rat).
BACKGROUND
Diabetic nephropathy is caused by multiple factors related to the altered metabolic environment in diabetes mellitus (DM). Experimental diabetic kidney disease is characterized by renal hypertrophy associated with increased tissue concentrations of insulin-like growth factor I (IGF-I). To assess the specific roles of serum insulin and glucose in mediating the development of diabetic nephropathy, the effects of both hyperinsulinaemic and hypoinsulinaemic DM were studied in Psammomys obesus (sand rat), a model of type 2 DM.


METHODS
The IGF-I system was studied in normal Psammomys obesus gerbils and at 5, 15 and 70 days after the induction of either hyper- or hypoinsulinaemic DM. To induce hyperinsulinaemic DM, Psammomys were raised on a high-energy diet. Hypoinsulinaemic DM was induced by either administration of streptozotocin or a specially designed diet.


RESULTS
Hyperinsulinaemic hyperglycaemic Psammomys did not exhibit renal hypertrophy (unchanged kidney/body-weight ratio) and renal IGF-I levels were in the normal range on days 5, 15 and 70. In contrast, Psammomys with hypoinsulinaemic hyperglycaemia induced either by streptozotocin injection or by pancreas exhaustion brought on by a long-term caloric excess diet, had significant increases in kidney/body-weight ratio which were associated with elevated renal IGF-I and mRNA and protein levels of kidney IGF binding protein I.


CONCLUSIONS
This study shows that serum insulin levels in the presence of hyperglycaemia have an important role in the development of experimental diabetic nephropathy in the Psammomys model. The implication of this finding is that the pathophysiological mechanisms for diabetic kidney disease in experimental models may be different for type 1 and type 2 DM.
Raz
Itamar
I
Diabetes Center and Department of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel.
Wexler
Isaiah
I
Weiss
Ofra
O
Flyvbjerg
Allan
A
Segev
Yael
Y
Rauchwerger
Ariella
A
Raz
Gadi
G
Khamaisi
Mogher
M
D000818:Animals; D001786:Blood Glucose / Q000032:analysis* / Q000502:physiology*; D003920:Diabetes Mellitus / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D006984:Hypertrophy / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000097:blood*; D007328:Insulin / Q000097:blood* / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000502:physiology*; D007668:Kidney / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007334:Insulin-Like Growth Factor I