Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.

• MeSH
• atorvastatin farmakologie   metabolismus   MeSH
• beta-buňky * MeSH
• exenatid farmakologie   metabolismus   MeSH
• inzulin metabolismus   MeSH
• LDL-receptory metabolismus   MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 metabolismus   farmakologie   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   farmakologie   MeSH
• sekrece inzulinu MeSH
• statiny * farmakologie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

Phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) from mature maize seeds (Zea mays L.) was purified to homogeneity and a final specific activity of 13.3 μmol min⁻¹ mg⁻¹. Purified PEPC was treated with phosphatase from bovine intestinal mucosa or protein kinase A to study its apparent phosphorylation level. Kinetic parameters of the enzyme reaction catalyzed by phosphorylated and dephosphorylated forms under different conditions were compared, as well as an effect of modulators. The enzyme dephosphorylation resulted in the change of hyperbolic kinetics to the sigmoidal one (with respect to PEP), following with the decrease of maximal reaction rate and the increase of sensitivity to L-malate inhibition. The hyperbolic kinetics of native PEPC present in dry maize seeds was not changed after the protein kinase A treatment, while it was converted to the sigmoidal one after dephosphorylation. Level of PEPC phosphorylation was not affected during seed imbibition.

• MeSH
• fosfoenolpyruvátkarboxylasa antagonisté a inhibitory   izolace a purifikace   metabolismus   MeSH
• fosforylace MeSH
• kinetika MeSH
• kukuřice setá enzymologie   MeSH
• maláty farmakologie   MeSH
• proteinkinasy závislé na cyklickém AMP farmakologie   MeSH
• semena rostlinná enzymologie   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fixní kombinace léků MeSH
• flavonoidy farmakologie   MeSH
• inhibitory enzymů MeSH
• mitogenem aktivované proteinkinasy antagonisté a inhibitory   metabolismus   MeSH
• oxytocin antagonisté a inhibitory   farmakologie   MeSH
• prasata MeSH
• proteinkinasy závislé na cyklickém AMP antagonisté a inhibitory   farmakologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH