Iterative pulse administration of succinic acid monomethyl ester to streptozotocin diabetic rats.
In adult rats injected intravenously with streptozotocin (STZ: 20 or 40 mg/kg body wt) and examined 13 days later, the secretory response of the perfused pancreas to D-glucose is impaired. A paradoxical inhibition of insulin release is even observed in the perfused pancreas of rats given the high STZ dose. When pulses of succinate monomethyl ester (SAM: 60 mg) were administered intraperitoneally three times a day for one week from the 6th to 12th day after STZ injection, no obvious difference in insulin output from the perfused pancreas stimulated with either D-glucose or SAM was observed between SAM-treated and untreated rats first injected with the low STZ dose. However, in rats first injected with the high STZ dose, the secretory response to SAM was higher in SAM-treated than untreated animals. These findings raise the view that suitable non-glucidic nutrient secretagogues might improve, in a long term manner, the secretory potential of the endocrine pancreas in animal models of diabetes characterized by a preferential impairment of the B-cell response to D-glucose.
Akkan
A G
AG
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004032:Diet; D005260:Female; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D013386:Succinates / Q000008:administration & dosage*
D007328:Insulin; D013386:Succinates; D005947:Glucose; C041105:monomethyl succinate