Reduction of insulin and triglycerides delays glomerulosclerosis in obese Zucker rats.
To evaluate the effect of insulin and/or triglycerides on the pathogenesis of glomerulosclerosis, acarbose (BAYg5421), an inhibitor of intestinal alpha-glucosidases, was administered as a dietary admix (40 mg/100 g chow) to Zucker obese rats (ZOA), from 1.5 months until sacrifice at 1.5, 5, 8, 10 and 15 months. Obese (ZO) and lean (ZL) rats served as controls. Despite a similar food intake, ZOA weighed less than ZO at all ages. Acarbose reduced serum triglycerides at all ages, and insulin until 10 months. Glycemia remained normal in all groups. Proteinuria developed with age and to a greater degree in ZO than in ZOA rats. In ZL, a faint proteinuria appeared only in the oldest animals. Glomerulosclerosis, tubular and interstitial lesions rapidly affected ZO kidneys. These lesions were reduced in ZOA until 10 months. Acarbose did not modify the hypertrophy of the glomeruli that developed after three months, but slowed down the expansion of the mesangial domain seen in ZO. Thus, by reducing the amount of ingested glucose, acarbose yielded a normal glycemia with a lesser production of insulin and reduced renal impairment. Therefore, insulin could be a key factor involved in the pathogenesis of glomerulosclerosis, either directly or through a control of triglyceride concentrations.
Michel
O
O
Unité de Recherche Immunopathologie Humaine, INSERM U 430, Hôpital Broussais, Paris, France.
Heudes
D
D
Lamarre
I
I
Masurier
C
C
Lavau
M
M
Bariety
J
J
Chevalier
J
J
D020909:Acarbose; D000418:Albumins / Q000032:analysis; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D003176:Complement C3 / Q000032:analysis; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005920:Glomerular Mesangium / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D006937:Hypercholesterolemia / Q000378:metabolism; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007074:Immunoglobulin G / Q000032:analysis; D008854:Microscopy, Electron; D009765:Obesity; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014312:Trisaccharides / Q000494:pharmacology
D000418:Albumins; D003176:Complement C3; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D014312:Trisaccharides; D020909:Acarbose