Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes

Abstract

AimWe investigated the molecular mechanisms by which vildagliptin preserved pancreatic β cell mass and function.MethodsMorphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-Ay-TaJcl(KK-Ay) and C57BL/6JJcl (B6) mice aged 8 weeks which received either vildagliptin or a vehicle for 4 weeks.ResultsBody weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-Ay mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic β cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-Ay mice. The morphological results were consistent with the gene expression profiles.ConclusionVildagliptin increases β cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice.

Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes

“…Indeed, some anti-diabetic drugs, thiazolidine (Kanda et al, 2010;Kawasaki et al, 2005), DPP4 inhibitors (Hamamoto et al, 2013) and glucagon like peptide-1 receptor agonist (Shimoda et al, 2011), possess a protective effect upon β-cells. In the condition of normal glucose tolerance, β-cell proliferation capacity to various stimulations is gradually attenuated with age (Rankin and Kushner, 2009).…”

Combination of DPP-4 inhibitor and PPARγ agonist exerts protective effects on pancreatic β-cells in diabetic db/db mice through the augmentation of IRS-2 expression

“…Thiazolidine (TZD) (Kawasaki et al, 2005, Kanda et al, 2010, Campbell and Mariz, 2007, GLP-1 receptor agonist (Shimoda et al, 2011), and dipeptidyl peptidase-4 (DPP-4) inhibitor (Hamamoto et al, 2013, van Genugten et al, 2012 are known to ameliorate glycemic control and reduce the progression of β-cell dysfunction in human subjects as well as animal models. TZD, an artificial ligand activating nuclear receptor peroxisome proliferators-activated receptor (PPAR) γ, improves insulin sensitivity in the peripheral tissues and protects β-cells against gluco-lipotoxicity.…”

Survey of Chloramphenicol in Honeys from China

“…The reaction solution was discarded, and the wells were washed five times with a washing solution provided by the ELSIA kit. Before termination of the reaction, the color reaction was allowed to proceed at 25°C for 15 min in the dark [12]. The absorbance was determined at 450/630 nm using a multifunctional plate reader (TECAN Infinite M200Pro, Switzerland).…”