Dataset Information

Anti-insulin antiserum increases inositol phosphate accumulation in rat pancreatic islets.

ABSTRACT: The role of insulin in modulating phosphoinositide breakdown and accumulation of inositol phosphates was investigated in isolated rat pancreatic islets by using GPAIS (guinea-pig anti-insulin antiserum) that neutralizes effects of insulin in the medium. At either 3.0 mM- or 16.7 mM-glucose or 3.0 mM-glucose plus 10 microM-arecaidine propargyl ester (muscarinic receptor agonist), GPAIS (but not control serum) was able to increase InsP2 and InsP3, but not InsP, in myo-[3H] inositol-prelabelled islets. The effect of GPAIS on 3H incorporation into InsP3 was dose-dependent, with a half-maximal effect at a concentration able to bind 4004 +/- 163 microunits of insulin. A specific mass assay of the biologically relevant isomer Ins (1,4,5)P3 revealed a huge increase (greater than 3-folf). Formation of PtdIns, PtdInsP and PtdInsP2 was not affected by GPAIS. This is indirect evidence for an effect of insulin on inositide metabolism, and therefore endogenously released insulin may have led to an underestimation in earlier studies of effects of insulinotropic substances on inositol phosphate accumulation.

SUBMITTER: Verspohl EJ

PROVIDER: S-EPMC1131292 | biostudies-other | 1990 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundHyperglycemia induces activation of the c-Jun N-terminal kinase (JNK) pathway, which suppresses insulin gene expression and reduces DNA binding of pancreatic and duodenal homeobox factor (PDX)-1. This study aims to investigate the effects of a novel curcumin derivative (NCD) on JNK signaling pathway on insulin synthesis and secretion in streptozotocin (STZ)-treated rat pancreatic islets in vitro.MethodsIsolated rat pancreatic islets were divided into five groups: untreated control group; group treated with NCD (10 μM); group exposed to STZ (5 mM); group treated with NCD (10 μM) and then exposed to STZ (5 mM); and group exposed to STZ (5 mM) and then treated with NCD (10 μM). The pancreatic islets from all groups were used for DNA fragmentation assays and quantitative assessments of the JNK, Pdx1, glucose transporter-2 (GLUT2), heme oxygenase (HO)-1, transcription factor 7-like 2 (TCF7L2), and glucagon-like peptide (GLP)-1 gene expression levels. The intracellular calcium, zinc, and the phosphorylated and total JNK protein levels were assessed. The insulin (secreted/total) and C-peptide levels were examined in islet culture medium.ResultsNCD protected pancreatic islets against STZ-induced DNA damage, improved total insulin (P = 0.001), secreted insulin (P = 0.001), and C-peptide levels (P = 0.001), normalized mRNA expressions of insulin, Pdx1, and GLUT2 (P = 0.0001), and significantly elevated calcium and zinc levels (P = 0.0001). All effects were significant when islets were treated with NCD before STZ (P = 0.05). JNK gene overexpression and JNK protein levels induced by STZ were significantly inhibited after NCD treatment of islets ( P = 0.0001). NCD-treated islets showed significantly elevated gene expressions of HO-1, TCF7L2, and GLP-1 (P = 0.0001), and these upregulated gene expressions were more significantly elevated with NCD treatment before STZ than after STZ (P = 0.05).ConclusionsNCD improved insulin synthesis and secretion in vitro in isolated pancreatic islets treated with STZ through inhibition of the JNK pathway, up-regulation of the gene expressions of HO-1, TCF7L2, and GLP-1 and enhancing effects on calcium and zinc levels.

Dataset Information

Anti-insulin antiserum increases inositol phosphate accumulation in rat pancreatic islets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets