Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-喂 was written by Sajan, Mini P.;Nimal, Sonali;Mastorides, Stephen;Acevedo-Duncan, Mildred;Kahn, C. Ronald;Fields, Alan P.;Braun, Ursula;Leitges, Michael;Farese, Robert V.. And the article was included in Metabolism, Clinical and Experimental in 2012.HPLC of Formula: 26832-08-6 This article mentions the following:
Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-mol. PKC-喂/位 inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-位, in which partial deficiency of muscle PKC-位 impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)]], binds to the substrate-binding site of PKC-位/喂, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PB1-binding domains of aPKC-位/喂/味 and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Akt, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-喂 in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)]] and aurothiomalate or similar agents that selectively inhibit hepatic aPKC may be useful treatments. In the experiment, the researchers used many compounds, for example, 1H-Imidazole-4-carboxamide (cas: 26832-08-6HPLC of Formula: 26832-08-6).
1H-Imidazole-4-carboxamide (cas: 26832-08-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.HPLC of Formula: 26832-08-6
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem