New Evidence on Hypoglycemic Effect of Quinolinic Acid in Diabetic Rats

Abstract

In the present study, the effects of administrating 4 mM and 300 mg kg(-1) b.wt. of quinolinic acid were studied, in vitro and in vivo, respectively, to evaluate its inhibitory activity on phosphoenolpyruvate carboxykinase in diabetic rats. The results of in vitro studies have clearly indicated the inhibitory effect of quinolinic acid on enzyme activity. The hill plot showed the binding stoichiometry of quinolinic acid per enzyme to be 4:1. The in vivo studies showed that intra peritoneal injection of 300 mg kg(-1) b.wt. initiates reduction of blood glucose level in 1 h after injection, restoring the blood glucose to its normal level at 2 h post injection and keeping it constant for at least further 4 h. Based on present results we concluded that quinolinic acid and hence its precursor tryptophan having induced obvious hypoglycemic effects in normal and diabetic rats at high enough concentrations, they are worthy of further study and research for their hyperglycemic effect in other diabetic animal models.

Kynurenine Pathway in Chronic Kidney Disease: What’s Old, What’s New, and What’s Next?

“…10,26 They play a significant role in the modulation of several physiological, as well as pathological processes, including redox homeostasis, gluconeogenesis, diabetic retinopathy, inflammation, carcinogenesis, and apoptosis. 19,[27][28][29][30][31][32][33][34][35][36] Numerous KYN derivatives demonstrated toxic effects on the body's cells at higher concentrations. To a large extent, this effect is related to their ability to induce and potentiate…”

“…Therefore, its excessive activation, by the elevated concentration of KYN and its metabolites, may accelerate cell aging processes and their death rate. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] The effects of the toxic properties of accumulated metabolites of the kynurenine pathway, both through the propagation of oxidative stress by KYN, 3-HKYN, 3-HAA, and QA and overstimulation of the AhR mainly by KYN and KYNA, as well as other mechanisms, such as the formation of complexes with insulin by XA or QA excitotoxic properties, may manifest themselves clinically in the form of systemic disorders, such as anemia, hypercoagulability, atherosclerosis, insulin resistance, kidney tissue damage, neurological disorders, changes in blood pressure, and osteodystrophy (Table 1). [26][27][28][29][30][31][32][33][34][35][36][41][42][43] Over the years, Table 1.…”

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401

“…Kynurenine (KYN), the major metabolite of TRP, is synthesized in the body by the tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) [12][13][14]. Metabolites of the kynurenine pathway play crucial roles in several physiological and pathophysiological processes [15][16][17][18][19][20][21][22][23][24]. Recent reports indicate that they are also connected with osteoblast proliferation and differentiation, and they can be related to the pathophysiology of osteoporosis [25,26].…”

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

“…TRP is the precursor not only to the serotonin but also and primarily to kynurenine metabolites (Schwarcz, 2004). Kynurenine pathway plays a crucial role in several processes, including redox homeostasis (Gonzalez Esquivel et al, 2017), gluconeogenesis (Dayer, Safari & Dayer, 2009), diabetic retinopathy (Munipally et al, 2011), inflammation (Heyes et al, 1992), carcinogenesis (Prendergast, 2011), and apoptosis (Fallarino et al, 2002). The knowledge of the role of the kynurenine pathway in bone metabolism is limited.…”