Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent diabetic rats after short-term infusion of succinic acid monomethyl ester.
The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings raise the question of whether a more prolonged administration of SME is required to raise the insulin store and improve the secretory potential of the endocrine pancreas in animals with type 2 diabetes.
Giroix
M H
MH
Laboratory of Nutrition Physiopathology, URA CNRS 307, University of Paris VII, France.
Sener
A
A
Portha
B
B
Malaisse
W J
WJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D007262:Infusions, Intravenous; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*
D013386:Succinates; D013311:Streptozocin; C041105:monomethyl succinate