Identification of tryptophan metabolites in the healthy epidermis of diabetics

Calandra, P

doi:10.1007/bf02624661

Cited by 6 publications

(3 citation statements)

References 6 publications

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“…Previous studies assessed KP metabolites in urine [21], and skin [22] of T2D patients. Serum KYN metabolites were evaluated only in patients with diabetic retinopathy, a complication of both T2D and T1D [23].…”

Section: Discussionmentioning

confidence: 99%

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Oxenkrug

2015

Mol Neurobiol

130

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About 350 million people worldwide have type 2 diabetes (T2D). The major risk factor of T2D is impaired glucose tolerance (pre-diabetes) with 10% of pre-diabetes subjects develop T2D every year. Understanding of mechanisms of development of T2D from pre-diabetes is important for prevention and treatment of T2D. Chronic stress and chronic low grade inflammation are prominent risk factors for T2D development in pre-diabetic subjects. However, molecular mechanisms mediating effect of stress and inflammation on development of T2D from pre-diabetes remain unknown. One of such mechanisms might involve kynurenine (KYN) pathway (KP) of tryptophan (TRP) metabolism. We suggested that chronic stress- or chronic low grade inflammation-induced upregulation of formation of upstream KTP metabolites, KYN and 3-hydroxyKYN, combined with chronic stress or chronic low grade inflammation-induced deficiency of pyridoxal 5'-phosphate, a cofactor of downstream enzymes of KTP, triggers overproduction of diabetogenic downstream KYN metabolites, kynurenic acid (KYNA) and 3-hydroxyKYNA (also known as xanthurenic acid (XA)). As the initial assessment of our working hypothesis, we evaluated plasma levels of up- and down-stream KP metabolites in the same samples of T2D patients. KYN, XA and KYNA levels in plasma samples of T2D patients were higher than in samples of non-diabetic subjects. Our results provide further support of “kynurenine hypothesis of insulin resistance and its progression to T2D” that suggested that overproduction of diabetogenic KP metabolites, induced by chronic stress- or chronic low grade inflammation, is one of the mechanisms promoting development of T2D from pre-diabetes. Downstream metabolites of KP might serve as biomarkers of T2D and targets for clinical intervention.

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Section: Discussionmentioning

confidence: 99%

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Oxenkrug

2015

Mol Neurobiol

130

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“…KYN pathway of TRP metabolism could be considered as a new target for prevention and treatment of depression, and aging/aging-associated medical (e.g., IR, obesity, cardiovascular), psychiatric (e.g., vascular cognitive impairment) and other disorders associated with chronic inflammation (e.g., HCV infection [68, 69, 105], psoriasis [106, 107]) disorders.…”

Section: Brecent Developmentsmentioning

confidence: 99%

Serotonin – Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments

Oxenkrug¹

2013

CDT

143

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In the late 60th - early 70th of the last century Prof. IP Lapin (June 26, 1930 – August 23, 2012) suggested that “intensification of central serotoninergic processes is a determinant of the thymoleptic (mood elevating) component” while “activation of noradrenergic processes is responsible for psychoenergetic and motor-stimulating component of the clinical antidepressant effect”. He suggested that in depression cortisol-inducible activation of liver enzyme, tryptophan 2,3-dioxygenase (TDO), shunted “metabolism of tryptophan away from serotonin production towards kynurenine production” leading to serotonin deficiency. He was the first to suggest and discover that kynurenine and its metabolites affect brain functions, and propose the role of neurokynurenines in pathogenesis of depression and action mechanisms of antidepressant effect. Further major developments of serotonin-kynurenine hypothesis include the discovery of antidepressant and cognition-enhancing effects of post-serotonin metabolite, N-acetylserotonin, an agonist to tyrosine kinase B(TrkB) receptors of brain derived neurotrophic factor. The discovery of indoleamine 2,3–dioxygenase (IDO), another rate-limiting enzyme of TRY – KYN metabolism, located in brain and inducible by pro-inflammatory cytokines, suggested the link between depression and aging/aging-associated medical (e.g., insulin resistance, obesity, cardiovascular), psychiatric (e.g., vascular cognitive impairment) and other disorders associated with chronic inflammation (e.g., hepatitis virus C, psoriasis) disorders.

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“…Secondly, it is possible that in diabetes the endogenous production of NAD from tryptophan remains at a subnormal to normal level, as indicated by findings of increased picolinic acid carboxylase activity and possibly other disturbances occurring prior to the quinolinic acid step (Figure 3)88–92. Therefore, a pyridine nucleotide deficiency, relative to the demand of an elevated glucose utilization, may occur frequently during the long‐term clinical course of diabetes32 (Figure 2).…”

Section: Chronic Disturbances Of Pyruvate Formation From Glucose and mentioning

confidence: 99%

Pyridine nucleotides in glucose metabolism and diabetes: a review

Wahlberg

Adamson

Svensson

2000

Diabetes Metab. Res. Rev.

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Nicotinamide adenine dinucleotide (NAD) and its derivatives NADH, NADP and NADPH have regulatory functions in the generation of triose phosphates and pyruvate from glucose. In many studies of the influence of the diabetic state on relationships between pyridine nucleotide and glucose metabolism, the focus has been on the sorbitol pathway. Less attention has been paid to other aspects of the role of pyridine nucleotides in pyruvate formation from glucose, in particular the effects of the NAD precursors nicotinamide and nicotinic acid on glucose metabolism. This paper reviews current knowledge of the involvement of pyridine nucleotides and their precursors in glucose catabolism in the normal and diabetic state. Reference is also made to the following three current hypotheses for mechanisms underlying diabetic microangiopathy: Chronic glucose overutilization, caused by hyperglycemia, in tissues which lack insulin receptors and therefore are freely permeable to glucose. Enhancement of sorbitol pathway activity with an ensuing decrease in the ratio of NAD/NADH. Enhanced utilization of both glucose and pyridine nucleotides in formation of triose phosphates and pyruvate. Therapy with NAD precursors like nicotinamide might have corrective effects on these proposed biochemical aberrations, thereby retarding progression of microangiopathy. Copyright © 2000 John Wiley & Sons, Ltd.

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Identification of tryptophan metabolites in the healthy epidermis of diabetics

Cited by 6 publications

References 6 publications

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Serotonin – Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments

Pyridine nucleotides in glucose metabolism and diabetes: a review

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Identification of tryptophan metabolites in the healthy epidermis of diabetics

Cited by 6 publications

References 6 publications

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes

Serotonin &ndash; Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments

Pyridine nucleotides in glucose metabolism and diabetes: a review

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Serotonin – Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments