Attenuation of high sucrose diet–induced insulin resistance in tryptophan 2,3-dioxygenase deficient Drosophila melanogaster vermilion mutants
Open accessAbstract
Exposure to high sugar diet (HSD) serves as an experimental model of insulin resistance (IR) and type 2 diabetes (T2D) in mammals and insects. Peripheral IR induced by HSD delays emergence of pupae from larvae and decreases body weight of Drosophila imago. Understanding of mechanisms of IR/T2D is essential for refining T2D prevention and treatment strategies. Dysregulation of tryptophan (TRP) - kynurenine (KYN) pathway was suggested as one of the mechanisms of IR development. Rate-limiting enzyme of TRP - KYN pathway in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. In insects TDO is encoded by vermilion gene. TDO is not active in vermilion mutants. In order to evaluate the possible impact of deficient formation of KYN from TRP on the inducement of IR by HSD, we compared the effect of HSD in wild type (Oregon) and vermilion mutants of Drosophila melanogaster by assessing the time of white pupae emergence from larva and body weight of imago. Delay of emergence of pupae from larvae induced by high sucrose diet was less pronounced in vermilion (1.4 days) than in Oregon flies (3.3 days) in comparison with flies maintained on standard diet. Exposure to high sucrose diet decreased body weight of Oregon (but not vermilion) imago. Attenuation of high sucrose diet-induced IR/T2D in vermilion flies might depend on deficiency of TRP - KYN pathway. Besides IR/T2D, HSD induces obesity in Drosophila. Future studies of HSD-induced obesity and IR/T2D in TDO deficient vermilion mutants of Drosophila might help to understand the mechanisms of high association between IR/T2D and obesity. Modulation of TRP - KYN metabolism might be utilized for prevention and treatment of IR/T2D.
AI snapshot
Written from the paper’s full text.
TL;DR
High-sucrose feeding caused less pupariation delay and no adult weight loss in tryptophan 2,3-dioxygenase–deficient vermilion Drosophila than in wild-type Oregon flies. The authors interpret this as attenuation of diet-induced insulin resistance when the tryptophan–kynurenine pathway is impaired.
Key findings
- High sucrose diet delayed emergence of white pupae from larvae by 3.3 days in Oregon wild-type flies but only 1.4 days in vermilion mutants, relative to standard diet.
- High sucrose diet reduced body weight of Oregon male imagoes by 37%, while vermilion male imagoes showed no diet-related weight change.
- On standard diet, Oregon pupae emerged 16% earlier than vermilion pupae, and baseline body weights of male Oregon and vermilion imagoes did not differ.
- The authors conclude that high-sucrose-induced insulin resistance is attenuated in TDO-deficient vermilion mutants, suggesting a role for the tryptophan–kynurenine pathway.
Methods
- Wild-type Oregon and vermilion mutant Drosophila melanogaster were kept at 23°C under a 12:12 light:dark cycle on standard medium; sucrose (0.67 M) was added before synchronized egg laying.
- Outcomes were time from synchronized egg laying to white pupae emergence and body weight of male imagoes weighed in groups of 10.
- Data came from three replicated experiments, expressed as mean ± standard deviation, and compared using two-tailed Mann-Whitney tests.
Limitations
- The paper does not state limitations.
- Evident from the text: insulin resistance is inferred indirectly from pupariation delay and adult weight, not measured directly; sample sizes and exact group numbers are not reported; only male imagoes were weighed; and the comparison uses one wild-type strain and one mutant strain.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 41 cited sources checked · 0 supported · 0 flagged
- Findingown data
The delay in pupal emergence caused by high sucrose diet is shorter in vermilion mutants (1.4 days) than in Oregon wild-type flies (3.3 days) compared with standard diet.
“Delay of emergence of pupae from larvae induced by high sucrose diet was less pronounced in vermilion (1.4 days) than in Oregon flies (3.3 days) in comparison with flies maintained on standard diet.”
- Also stated in: § Pupae emergence from larva · plain
“High sucrose diet-induced delay of pupae emergence from larvae was shorter in vermilion than in Oregon flies (Table 1).”
Quote in the paperSubstantial claim - Also stated in: § Pupae emergence from larva · plain
- Findingown data
Male adult body weights did not differ between Oregon and vermilion flies kept on standard diet.
“There were no differences in body weight of male imago Oregon and vermilion flies maintained on standard nutrition medium (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
On standard diet, Oregon wild-type flies emerged as pupae 16% faster than vermilion mutants.
“Emergence time of pupae from larva of Oregon flies maintained on standard nutrition medium was 16% shorter than emergence time of vermilion flies (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
High sucrose diet had no effect on adult body weight in vermilion mutants.
“In vermilion mutants high sucrose diet did not affect body weight of imago.”
Quote in the paperNot a substantial claim - Findingown data
High sucrose diet reduced adult body weight by 37% in Oregon wild-type flies.
“High sucrose diet decreased body weight of wild type flies (Oregon) imago by 37%.”
Quote in the paperNot a substantial claim
- Premisecitation
Dysregulation of the tryptophan-kynurenine pathway has been proposed as a mechanism contributing to insulin resistance development.
“Dysregulation of tryptophan (TRP) – kynurenine (KYN) pathway was suggested as one of the mechanisms of IR development.”
- Also stated in: § Introduction · hedged
“Dysregulation of kynurenine (KYN) pathway of tryptophan (TRP) metabolism (KP) was suggested as one of the mechanisms of development of IR and T2D [3–7].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Introduction · hedged
- Premisecitation
The larval-to-pupal transition in Drosophila is initiated by the steroid hormone ecdysone.
“Transition from larva to pupae in Drosophila is triggered by a steroid hormone, ecdysone [16].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
Reduced insulin resistance in KP-deficient vermilion mutants may lessen the high-sugar-diet-induced delay in larval-to-pupal transition by promoting ecdysone production.
“Attenuation of IR development in KP deficient vermilion mutants might attenuate HSD-induced delay of transition from larvae to pupae by facilitation of ecdysone formation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
High sugar diets serve as a model to study insulin resistance and type 2 diabetes in both mammals and insects.
“Exposure to high sugar diet (HSD) serves as an experimental model of insulin resistance (IR) and type 2 diabetes (T2D) in mammals and insects.”
- Also stated in: § Introduction · plain
“Exposure to high sugar diet (HSD) induces experimental model of IR/T2D in mammals [10] and insects [11].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Introduction · plain
- Interpretationreasoning
In mammals, high sugar diet may induce insulin resistance through increased production of the diabetogenic kynurenine derivatives xanthurenic acid and kynurenic acid.
“Therefore, inducement of IR by HSD might be mediated via increased production of diabetogenic KYN derivatives, XA and KYNA, in mammals (Figure 1).”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [25]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [26]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
The reduced insulin resistance in vermilion flies under high sugar diet is most likely due to TDO deficiency.
“Attenuation of HSD-induced IR in vermilion flies most likely depends on deficiency of TDO.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Rests on an assumption: The rate-limiting enzyme of the tryptophan–kynurenine pathway in Drosophila is TDO, which is encoded by the vermilion gene.
- Premisecitation
Insulin stimulates the production of ecdysone.
“Considering that insulin activates ecdysone formation, HSD-induced resistance to insulin effects might impair ecdysone formation and, consequently, delay pupariation [16].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Clinical and experimental research has indicated that xanthurenic acid and kynurenic acid have diabetogenic effects.
“Clinical and experimental studies suggested that XA and KYNA exert diabetogenic effects [22–26].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [25]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [26]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
The enzyme TDO lacks activity in vermilion mutant Drosophila melanogaster.
“TDO is not active in vermilion mutants.”
- Also stated in: § Introduction · plain
“TDO is inactive in vermilion mutants of Drosophila melanogaster [14].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Introduction · plain
- Interpretationreasoning
The development of insulin resistance caused by high sucrose diet is reduced in vermilion mutants relative to wild-type Drosophila.
“Considering that HSD-induced delayed emergence of pupae and decreased body weight is caused by IR [11–13], our data suggest that inducement of IR by high sucrose diet is attenuated in vermilion mutants in comparison with wild type Drosophila.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [12]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data
The current findings suggest that kynurenine pathway disturbances are one mechanism by which high sugar diet leads to insulin resistance and type 2 diabetes.
“Present data suggest disturbances of KP as one of the mechanisms mediating HSD-induced IR/T2D.”
Quote in the paperSubstantial claim
- May combine two claims. 4
- Classified as probably not a substantial claim. 4
May combine two claims.
PremisecitationHigh sugar diet leads to metabolic disturbances such as high blood sugar, high insulin, and insulin resistance in Drosophila.
“HSD causes metabolic dysfunction, including hyperglycemia, hyperinsulinemia, and IR in Drosophila [12].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationCortisol activates TDO, the rate-limiting enzyme of the kynurenine pathway, which converts tryptophan into active metabolites such as kynurenine.
“Cortisol activates TDO, rate-limiting enzyme of KP, that converts TRP into a number of biologically active metabolites, including KYN, a precursor of kynurenic acid (KYNA) and xanthurenic acid (XA) [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationPeripheral insulin resistance caused by high sugar diet delays pupal emergence from larvae and reduces body weight in Drosophila adults.
“Peripheral IR induced by HSD delays emergence of pupae from larvae and decreases body weight of Drosophila imago.”
- Also stated in: § Introduction · plain
“Peripheral IR induced by HSD delays emergence of pupae from larvae and decreased body weight of imago [11–13].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [12]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Introduction · plain
Classified as probably not a substantial claim. May combine two claims.
PremisecitationKynurenine pathway dysregulation in obesity has been proposed and supported by clinical and experimental findings.
“Dysregulation of KP in obesity was suggested [3–7] and supported by clinical and experimental data [31–34].”
Quote in the paperSubstantial claim0 of 9 sources checked- cites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [34]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHigh sugar diet also causes obesity in Drosophila.
“It is noteworthy that in Drosophila HSD induces not only IR/T2D but obesity as well [11].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataStatistical analyses were based on data from three replicated experiments.
“Statistics data from three replicated experiments was used for the statistical analyses.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThere is a strong association between obesity and type 2 diabetes.
“Obesity is highly associated with T2D [30].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
The rate-limiting enzyme of the tryptophan–kynurenine pathway in Drosophila is TDO, which is encoded by the vermilion gene.
“Rate-limiting enzyme of TRP – KYN pathway in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. In insects TDO is encoded by vermilion gene.”
“Rate-limiting enzyme of KP in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO, that is encoded by vermilion gene.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Pupal-emergence delays are not threefold apart
MinorThe reported delays are 3.3 days in Oregon flies and 1.4 days in vermilion flies. Their ratio is about 2.36, not three.
Reported 3 · recomputed 2.357143
“high sucrose diet induced three times shorter delay of pupae emergence from larvae”
Cites
Obesity and diabetes: the increased risk of cancer and cancer-related mortality
Gallagher, E. J., & LeRoith, D. (2015) · Physiological Reviews · doi:10.1152/physrev.00030.2014 · Cited by 806 · see citing works
Antagonistic Actions of Ecdysone and Insulins Determine Final Size in Drosophila
Colombani, J., Bianchini, L., Layalle, S., Pondeville, E., Dauphin‐Villemant, C., Antoniewski, C., Carré, C., Noselli, S., & Léopold, P. (2005) · Science · doi:10.1126/science.1119432 · Cited by 620 · see citing works
Wang, Y., Lam, K. S. L., Kraegen, E. W., Sweeney, G., Zhang, J., Tso, A. W., Chow, W.-S., Wat, N. M., Xu, J. Y., Hoo, R. L., et al. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.075614 · Cited by 578 · see citing works
A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila
Musselman, L. P., Fink, J. L., Narzinski, K., Ramachandran, P. V., Hathiramani, S. S., Cagan, R. L., & Baranski, T. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.007948 · Cited by 564 · cited 4× · see citing works
“It is noteworthy that in Drosophila HSD induces not only IR/ T2D but obesity as well [11].”
BackgroundResultInfluentialEpidemiological Perspectives of Diabetes
Tao, Z., Shi, A., & Zhao, J. (2015) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-015-0598-4 · Cited by 331 · cited 1× · see citing works
“T2D is the 8th leading cause of death in the world [1].”
BackgroundOxenkrug, G. F. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8497-4 · Cited by 255 · cited 1× · see citing works
“Dysregulation of KP in obesity was suggested [3-7] and supported by clinical and experimental data [3134].”
ResultSelf-citationHigh Sugar-Induced Insulin Resistance in Drosophila Relies on the Lipocalin Neural Lazarillo
Pasco, M. Y., & Léopold, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036583 · Cited by 225 · cited 4× · see citing works
“HSD causes metabolic dysfunction, including hyperglycemia, hyperinsulinemia, and IR in Drosophila [12].”
BackgroundResultInfluentialOxenkrug, G. F. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05356.x · Cited by 221 · cited 1× · see citing works
“Dysregulation of KP in obesity was suggested [3-7] and supported by clinical and experimental data [3134].”
ResultSelf-citationChiodini, I., Torlontano, M., Scillitani, A., Arosio, M., Bacci, S., Di Lembo, S., Epaminonda, P., Augello, G., Enrini, R., Ambrosi, B., et al. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.02045 · Cited by 190 · see citing works
Mangge, H., Summers, K. L., Meinitzer, A., Zelzer, S., Almer, G., Prassl, R., Schnedl, W. J., Reininghaus, E. Z., Paulmichl, K., Weghuber, D., et al. (2013) · Obesity · doi:10.1002/oby.20491 · Cited by 186 · see citing works
Pedersen, E. R., Tuseth, N., Eussen, S. J. P. M., Ueland, P. M., Strand, E., Svingen, G. F. T., Midttun, Ø., Meyer, K., Mellgren, G., Ulvik, A., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304674 · Cited by 171 · cited 5× · see citing works
“Recently reported elevation of plasma levels of major derivatives of KP in T2D and a strong correlation between dysregulation of KP and severity of IR might further support the suggestion of KP involvement in mechanisms of IR/T2D [8,9].”
BackgroundInfluentialGenetic and Hormonal Regulation of Tryptophan–Kynurenine Metabolism
Oxenkrug, G. F. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1403.003 · Cited by 163 · see citing works
Self-citationTryptophan metabolism: entering the field of aging and age-related pathologies
van der Goot, A. T., & Nollen, E. A. A. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.02.007 · Cited by 163 · see citing works
Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes
Oxenkrug, G. F. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9232-0 · Cited by 151 · cited 5× · see citing works
“Recently reported elevation of plasma levels of major derivatives of KP in T2D and a strong correlation between dysregulation of KP and severity of IR might further support the suggestion of KP involvement in mechanisms of IR/T2D [8,9].”
BackgroundInfluentialSelf-citationA high-sugar diet produces obesity and insulin resistance in wild-type Drosophila
Musselman, L. P., Fink, J. L., Narzinski, K., Ramachandran, P. V., Hathiramani, S. S., Cagan, R. L., & Baranski, T. (2011) · Journal of Cell Science · doi:10.1242/jcs.102947 · Cited by 134 · see citing works
Wolowczuk, I., Hennart, B., Leloire, A., Bessede, A., Soichot, M., Taront, S., Caiazzo, R. J., Raverdy, V., Pigeyre, M., Guillemin, G. J., et al. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00373.2011 · Cited by 118 · see citing works
Chronic Immune Activation Underlies Morbid Obesity: Is IDO A Key Player?
Brandacher, G., Hoeller, E., Fuchs, D., & Weiss, H. G. (2007) · Current Drug Metabolism · doi:10.2174/138920007780362590 · Cited by 111 · see citing works
The role of the kynurenine pathway of tryptophan metabolism in cardiovascular disease
Polyzos, K. A., & Ketelhuth, D. F. J. (2015) · Hämostaseologie · doi:10.5482/hamo-14-10-0052 · Cited by 93 · see citing works
Rovenko, B. M., Perkhulyn, N. V., Gospodaryov, D. V., Sanz, A., Lushchak, O. V., & Lushchak, V. I. (2014) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2014.11.008 · Cited by 85 · cited 2× · see citing works
“Peripheral IR induced by HSD delays emergence of pupae from larvae and decreased body weight of imago [11-13].”
BackgroundResultLam, C., Chari, M., Su, B., Cheung, G. W. C., Kokorovic, A., Yang, C. S., Wang, P. Y. T., Lai, T. Y. Y., & Lam, T. K. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.087338 · Cited by 83 · see citing works
Patterson, A. D., Bonzo, J. A., Li, F., Krausz, K. W., Eichler, G. S., Aslam, S., Tigno, X. T., Weinstein, J. N., HANSEN, B. C., Idle, J. R., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.221739 · Cited by 77 · see citing works
Lipocalins and Insulin Resistance: Etiological Role of Retinol-Binding Protein 4 and Lipocalin-2?
van Dam, R. M., & Hu, F. B. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.080432 · Cited by 57 · see citing works
Elahi-Moghaddam, Z., Rassouli, M. B., Mahdavi-Shahri, N., et al. (2013) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/2251-6581-12-9 · Cited by 47 · see citing works
Herder, C., Nuotio, M.-L., Shah, S., Blankenberg, S., Brunner, E. J., Carstensen, M., Gieger, C., Grallert, H., Jula, A., Kähönen, M., et al. (2014) · Diabetes · doi:10.2337/db14-0731 · Cited by 46 · see citing works
Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA).
Kotake, Y., Ueda, T., Mori, T., et al. (1975) · PubMed · Cited by 44 · see citing works
Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients
Oxenkrug, G. F., Turski, W. A., Zgrajka, W., Weinstock, J. V., & D, P. S. M. (2013) · Hepatitis Research and Treatment · doi:10.1155/2013/149247 · Cited by 42 · see citing works
Self-citationIndoleamine 2,3-diooxygenase in periaortic fat: mechanisms of inhibition of contraction
Watts, S. W., Shaw, S. J., Burnett, R. J., & Dorrance, A. M. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00384.2011 · Cited by 41 · see citing works
The role of kynurenines in diabetes mellitus
Connick, J. H., & Stone, T. W. (1985) · Medical Hypotheses · doi:10.1016/0306-9877(85)90104-5 · Cited by 32 · cited 1× · see citing works
“Dysregulation of KP in obesity was suggested [3-7] and supported by clinical and experimental data [3134].”
ResultReal, M. D., & Ferré, J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39128-8 · Cited by 18 · see citing works
Ikeda, S., & Kotake, Y. (1986) · PubMed · Cited by 16 · see citing works
FACTORS AFFECTING THE INTRACELLUALR SYNTHESIS OF KYNURENINE
Rizki, T. M., & Rizki, R. M. (1964) · The Journal of Cell Biology · doi:10.1083/jcb.21.1.27 · Cited by 15 · cited 2× · see citing works
“In Drosophila, TDO-regulated KYN formation from TRP begins at the end of the third larval instar in the cells of the anterior region of fat body (analog of liver and fat tissues in humans) [14].”
BackgroundFructose diet and VEGF-induced plasma extravasation in hamster cheek pouch.
Félétou, M., Boulanger, M., Staczek, J., et al. (2003) · PubMed · Cited by 14 · see citing works
Oxenkrug, G. F. (2015) · Molecular and integrative toxicology · doi:10.1007/978-3-319-15630-9_8 · Cited by 8 · cited 1× · see citing works
“Dysregulation of KP in obesity was suggested [3-7] and supported by clinical and experimental data [3134].”
ResultSelf-citationAn oral amino acid loading test before and after intestinal bypass operation for morbid obesity.
Kihlberg, R., Bark, S., & Hallberg, D. (1982) · PubMed · Cited by 6 · see citing works
Navrotskaya, V., Oxenkrug, G. F., Vorobyova, L., Sharma, H. S., Muresanu, D. F., & D, P. S. M. (2014) · American Journal of Neuroprotection and Neuroregeneration · doi:10.1166/ajnn.2014.1083 · Cited by 5 · cited 1× · see citing works
“Emerging time was taken as the period from the time of synchronized egg laying to the time of larvae emergency into white pupae as described elsewhere [15].”
BackgroundSelf-citation
Flagged first, then by citations
Cited by
Sorted by citations
Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases
Song, P., Ramprasath, T., Wang, H., & Zou, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2504-2 · Cited by 245 · see citing works
“TDO inactive mutation attenuates high sucrose diet-induced insulin resistance (IR) in Drosophila, suggesting that upregulated KP mediates high sucrose diet-induced IR [135].”
Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications
Ye, Z., Yue, L., Shi, J., Shao, M., & Wu, T. (2019) · Journal of Cancer · doi:10.7150/jca.31727 · Cited by 215 · see citing works
Oxenkrug, G. F., van der Hart, M., Roeser, J., & D, P. S. M. (2017) · Integrative Clinical Medicine · doi:10.15761/icm.1000105 · Cited by 33 · see citing works
“Discussion Present results (together with our previously published data) suggest that peripheral KMO deficiency is a common feature of MetS and schizophrenia.”
BackgroundInfluentialSelf-citationThe Genetics of Diabetes: What We Can Learn from Drosophila
Liguori, F., Mascolo, E., & Vernı̀, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011295 · Cited by 30 · see citing works
Migraine: A disorder of metabolism?
Kokavec, A. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2016.10.029 · Cited by 23 · see citing works
“…with: Kokavec, Halloran & Crowe, 2009 (i.e. reference 118) Query: The citation “Anantharaman-Barr and Decombaz (1988) and Navrotskaya et al. (2016)” has been changed to “Anantharaman-Barr and Decombaz (1989) and Navrotskaya et al. (2015)” to match the author name and date in the reference list.”
BackgroundKynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats.
Oxenkrug, G. F., Cornicelli, J. A., van der Hart, M., Roeser, J., & D, P. S. M. (2016) · PubMed · Cited by 16 · see citing works
Self-citationOxenkrug, G. F., & D, P. S. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01763-x · Cited by 15 · see citing works
Self-citationOxenkrug, G. F., & Navrotskaya, V. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231179411 · Cited by 13 · see citing works
Self-citationAdefegha, S. A., Ogunsuyi, O. B., & Oboh, G. (2020) · Comparative Clinical Pathology · doi:10.1007/s00580-020-03117-9 · Cited by 10 · see citing works
“The ability of dietary inclusion of 30% sucrose to induce elevated fly glucose and triglyceride levels in this study agrees with previous reports on the use of HSD in modeling diabetes-like phenotype in this flies at different developmental stages (Musselman et al. 2011; Navrotskaya et al. 2015; Ecker et al. 2017).”
BackgroundResultInfluentialNavrotskaya, V., Oxenkrug, G. F., Vorobyova, L., & D, P. S. M. (2016) · PubMed · Cited by 11 · see citing works
Self-citationSathyasaikumar, K. V., Breda, C., Schwarcz, R. M., & Giorgini, F. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7825-0_18 · Cited by 9 · see citing works
Dysfunction of Mitochondrial Dynamics in Drosophila Model of Diabetic Nephropathy
Kim, K., Joo, S. H., Choi, H., et al. (2021) · Life · doi:10.3390/life11010067 · Cited by 8 · see citing works
Francikowski, J., Potrzebska, M., Szulińska, E., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-00393-5 · Cited by 2 · see citing works
Navrotskaya, V., & Sapota, Y. Y. (2020) · Faktori eksperimental noi evolucii organizmiv · doi:10.7124/feeo.v26.1244
Self-citation
- Authors
- Navrotskaya, V., Oxenkrug, G., Vorobyova, L., & Summergrad, P.
- Affiliations
- V. N. Karazin Kharkiv National University (UA)
- Tufts University (US)
- Venue
- Integrative Obesity and Diabetes
- Publisher
- Open Access Text Pvt, Ltd.
- Published
- 2015
- Volume
- 1
- Issue
- 4
- Pages
- 93-95
- ISSN
- 2056-8827 (ISSN-L)
- PMC
- PMC4503375
- OpenAlex
- W2416116491
- Cited by
- 14
- References
- 35
- Citations by year
- 2023: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Integrative Obesity and Diabetes (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R03MH104810)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- insulin resistance, type 2 diabetes, high-sucrose diet, tryptophan 2,3-dioxygenase, kynurenine pathway, Drosophila melanogaster, pupal emergence, body weight, obesity, kynurenine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read under definition version 3 (extract-v3) on 2026-09-28.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
