The role of lactate dehydrogenase (LDH) in the generation of the metabolic signal for insulin secretion was studied after stable overexpression in INS-1 and RINm5F insulin-producing cells. INS-1 cells with a 25-fold overexpression of LDH-A, the highest level achieved, showed a 20-30% decrease in the glucose oxidation rate at glucose concentrations above 5 mM when compared with control cells, wh...

OBJECTIVE In diabetes, β-cell mass is not static but in a constant process of cell death and renewal. Inactivating mutations in transcription factor 1 (tcf-1)/hepatocyte nuclear factor1a (hnf1a) result in decreased β-cell mass and HNF1A-maturity onset diabetes of the young (HNF1A-MODY). Here, we investigated the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on the rege...

We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol (PI) 3-kinase- and protein kinase C zeta-dependent manner. However, the exact mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to pro...

The role of Ins(1,4,5)P3 in receptor-induced Ca2+ mobilization in pituitary cells was studied at the single-cell level. Experimental strategies were developed which allowed a comparative analysis of the effects of Ins(1,4,5)P3 with those of receptor activation under identical conditions. These include microfluorimetry as well as a novel technique which permits the controlled and rapid applicati...

Dictyostelium discoideum cells that overexpress a ras gene with a Gly12----Thr12 mutation (Dd-ras-Thr12) have an altered phenotype. These cells were labeled with [3H]inositol and the incorporation of radioactivity into inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] was analyzed and found to be higher than in control cells. In contrast, the total mass of Ins(1,4,5)P3, as assessed with an assay usin...

Background: MDM2 (Murine Double Minute2) is an oncoprotein that inhibits the P53 activity. Overexpression of MDM2 gene has been reported in several human tumors. In the present study, we aimed to evaluate the impact of 40-bp insertion/deletion (ins/del) polymorphism on the promoter of MDM2 and susceptibility to breast cancer in a sample of Iranian population. Methods: This case-control study wa...

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to ...

Cytokines mediate pancreatic islet beta-cell apoptosis and necrosis, leading to loss of insulin secretory capacity and type 1 diabetes mellitus. The cytokines, IL-1beta and interferon-gamma, induced terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining of rat islet cells within 48 h by about 25-30%, indicative of apoptosis and/or necrosis. S...

AIM Type 2 diabetes mellitus is characterized by lack of, or relative deficiency in, insulin productions and insensitivity of target tissues to insulin. Improvement of β-cell functions is a potential strategy for the clinical management of this disease. We reported before that geniposide improved glucose-stimulated insulin secretion with the activation of glucagon-like peptide 1 receptor (GLP-1...