Octreotide administration in diabetic rats: effects on renal hypertrophy and urinary albumin excretion.
Initial renal hypertrophy in experimental diabetes is prevented by administration of a long-acting somatostatin analogue octreotide (SMS). To investigate the long-term effects of SMS on renal hypertrophy and urinary albumin excretion (UAE), streptozotocin-diabetic and non-diabetic rats were treated with two daily subcutaneous injections of SMS (100 micrograms x 2) for six months. Untreated diabetic and non-diabetic animals were used as reference groups. No differences were seen between the two diabetic groups in respect to body weight, food intake, blood glucose levels, urinary glucose output, hemoglobin A1C(HbA1C), fructosamine, serum growth hormone (rGH) or creatinine clearance, but kidney weight (896 +/- 36 vs. 1000 +/- 24 mg, P less than 0.02), UAE (417 +/- 131 vs. 1098 +/- 187 micrograms/24 hr, P less than 0.02), kidney insulin-like growth factor I (IGF-I) (167 +/- 16 vs. 239 +/- 17 ng/g, P less than 0.01) and serum IGF-I (301 +/- 26 vs. 407 +/- 17 micrograms/liter, P less than 0.01) were all reduced in the SMS-treated diabetic animals when compared to the untreated diabetic group. In non-diabetic rats SMS reduced body weight (274 +/- 3 vs. 293 +/- 5 g, P less than 0.01), kidney weight (695 +/- 9 vs. 764 +/- 17 mg, P less than 0.01), UAE (83 +/- 29 vs. 364 +/- 114 micrograms/24 hr, P less than 0.02), kidney IGF-I (202 +/- 12 vs. 280 +/- 12 ng/g, P less than 0.01), serum IGF-I (428 +/- 21 vs. 601 +/- 54 micrograms/liter, P less than 0.01) and serum rGH (67 +/- 6 vs. 126 +/- 27 micrograms/liter, P less than 0.05) when compared to untreated controls. When kidney weights were expressed in relation to body weight no difference was found between SMS-treated and untreated controls, while the difference between SMS-treated and untreated diabetic animals was still present (P less than 0.01). In conclusion, chronic administration of SMS has abating effects on diabetic renal hypertrophy and UAE, and thus indicates that SMS may reduce development of diabetic kidney lesions in experimental diabetes. The long-term suppressive effects of SMS on renal enlargement and UAE may in part be mediated through reduction in circulating and kidney IGF-I levels.
Flyvbjerg
A
A
University of Aarhus, Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital, Denmark.
Marshall
S M
SM
Frystyk
J
J
Hansen
K W
KW
Harris
A G
AG
Orskov
H
H
D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000473:pathology*; D004435:Eating; D004573:Electrolytes / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015282:Octreotide / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains
D004573:Electrolytes; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide