Insulinotropic action of 1,2,3-Tri(methylsuccinyl)glycerol ester.

A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol ester (3SMG), was found to stimulate insulin release from rat pancreatic islets. In the presence of 7 mM d-glucose, a 10 microM concentration of 3SMG was sufficient to cause a significant increase in insulin output. The ester mimicked the effect of other nutrient secretagogues in enhancing the synthesis of islet peptides, with a preferential action on proinsulin as distinct from nonhormonal peptides, in decreasing 86Rb outflow from prelabeled islets, and in stimulating Ca2+ inflow into the islet cells. It is proposed, therefore, that 3SMG displays the attributes suitable for stimulation or potentiation of insulin release in noninsulin-dependent diabetes, without requiring administration in large amounts and, hence, without the risk of excessive hepatic gluconeogenesis.

[1]  W. Malaisse,et al.  Comparison between the insulinotropic potential of ten new esters of succinic acid. , 1998, European journal of pharmacology.

[2]  W. Malaisse,et al.  Stimulation of insulin release and potentiation of the insulinotropic action of antidiabetic agents by 1,2,3-tri(methylsuccinyl)glycerol ester in anaesthetized rats. , 1997, Pharmacological research.

[3]  W. Malaisse,et al.  Insulinotropic action of methyl pyruvate: enzymatic and metabolic aspects. , 1996, Archives of biochemistry and biophysics.

[4]  W. Malaisse,et al.  Dissociation between the potency and reversibility of the insulinotropic action of two meglitinide analogues. , 1996, Pharmacological research.

[5]  W. Malaisse.  The esters of carboxylic nutrients as insulinotropic tools in non-insulin-dependent diabetes mellitus. , 1995, General pharmacology.

[6]  W. Malaisse,et al.  In Vivo Stimulation of Insulin Secretion by Novel Esters of Succinic Acid , 1995, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[7]  W. Malaisse,et al.  Metabolic effects and fate of succinic acid methyl esters in rat hepatocytes. , 1994, Archives of biochemistry and biophysics.

[8]  I. Conget,et al.  Insulinotropic action of glutamic acid dimethyl ester. , 1994, The American journal of physiology.

[9]  W. Malaisse,et al.  Respiratory, ionic, and functional effects of succinate esters in pancreatic islets. , 1993, The American journal of physiology.

[10]  A. Boschero,et al.  The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XLII. Effects of Extracellular pH on Insulin Release: Their Dependency on Nutrient Concentration , 1980, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[11]  W. Malaisse,et al.  Regulation of 86Rb+ outflow from pancreatic islets I. Reciprocal changes in the response to glucose, tetraethylammonium and quinine , 1980, Molecular and Cellular Endocrinology.

[12]  W. Malaisse,et al.  Regulation of calcium fluxes in pancreatic islets: dissociation between calcium and insulin release. , 1978, The Journal of physiology.

[13]  W. Malaisse.  The beta cell in non-insulin-dependent diabetes: giving light to the blind , 1994 .

[14]  D. Vicent,et al.  Insulinotropic action of the dimethyl ester of glutamic acid in anaesthetised rats , 1994 .

[15]  W. Malaisse,et al.  Stimulation of protein biosynthesis in pancreatic islets by quinine , 1991 .

[16]  W. Clarke,et al.  Methods in diabetes research , 1984 .