The title compound (S)-3-(3-((7-ethynyl-9H-pyrimido[4,5-b]indol-4-yl)amino)piperidin-1-yl)propanenitrile (2) was synthesized in five steps, starting from 4-chloro-7-iodo-9H-pyrimido[4,5-b]indole (3), and characterized by 1H-NMR, 13C-NMR, MS HPLC. Moreover, its structure confirmed single crystal X-ray diffraction. Pyrimido[4,5-b]indole 2 demonstrated an IC50 value of 2.24 µM a NanoBRETTM TE intr...

The exposure of humans to fluorine is connected with its presence in the air, food and water. It well known that fluorides even at a low concentration but long time accumulate body lead numerous metabolic disorders. Fluoride recognised as factor modulating energy metabolism cells. This interaction particular importance muscle cells, which are cells high activity related glucose glycogen. In som...

Although mutations in the gamma-subunit of AMP-activated protein kinase (AMPK) can result in excessive glycogen accumulation and cardiac hypertrophy, the mechanisms by which this occurs have not been well defined. Because >65% of cardiac AMPK activity is associated with the gamma1-subunit of AMPK, we investigated the effects of expression of an AMPK-activating gamma1-subunit mutant (gamma1 R70Q...

Introduction: Glycogen Synthase Kinase-3β (GSK-3β) participates in several signaling pathways and plays a crucial role in neurodegenerative diseases, inflammation, and neuropathic pain. The ratio of phosphorylated GSK-3β over total GSK-3β (p-GSK-3β/t-GSK-3β) is reduced following nerve injury. Apoptosis is a hallmark of many neuronal dysfunctions in the context of neuropathic pain. Thus, this st...

The site(s) of action of a bovine pituitary diabetogenic peptide that produces hyperglycemia and hyperinsulinemia in vivo (dogs or humans) was investigated in vitro. When rat diaphragms were incubated with the peptide in the presence of insulin, the peptide depressed insulin-mediated (a) glucose uptake, (b) glycogen synthesis, and (c) glycogen synthase activation (conversion of D to I form). In...

Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. Here we show that despite markedly reduced glucose transport in muscle, muscle glycogen content in the fasted state is increased. We sought to determine the mechanism(s). Basal glycogen synthase activity is increased by 34% and glycogen phosphorylase activity is decreased...

A rabbit liver protein kinase (PCO.,), able to phosphorylate glycogen synthase and phosvitin, has been extensively purified. The enzyme had apparent M, = 170,000-190,000 as judged by gel filtration and was associated with two major polypeptide species, a (Mr = 43,000) and lp (Mr = 25,000). Two other polypeptides, Mr = 38,000 and M, = 35,000, were also detected. Treatment with trypsin led to an...

More than 40% of HIV-infected patients on highly active antiretroviral therapy (HAART) experience fat redistribution (lipodystrophy), a syndrome associated with insulin resistance primarily affecting insulin-stimulated nonoxidative glucose metabolism (NOGM(ins)). Skeletal muscle biopsies, obtained from 18 lipodystrophic nondiabetic patients (LIPO) and 18 nondiabetic patients without lipodystrop...

Glycogen synthase kinase 3 (GSK3) is a vital multifunctional molecule that widely distributed in invertebrates and vertebrates. GSK3 highly conserved serine/threonine (Ser/Thr) protein kinase, which plays an important role insulin, Wnt, various signaling pathways. In this study, gene were identified the genome of Pacific white shrimp, Litopenaeus vannamei , analyzed its structure, phylogeny, ex...

Various biological responses stimulated by insulin have been thought to be regulated by phosphatidylinositol 3-kinase, including glucose transport, glycogen synthesis, and protein synthesis. However, the molecular link between phosphatidylinositol 3-kinase and these biological responses has been poorly understood. Recently, it has been shown that protein kinase B (PKB/c-Akt/Rac) lies immediatel...