DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for glucose metabolism disease — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGlucose metabolism disease maps to a 14-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedMelatoninMelatonin receptor agonist
Structures already discussed alongside glucose metabolism disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of fad quinone reductase 2 — Melatonin has a real, experimentally solved structure in complex with this target (PDB 4QOG, 1.4 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet ml1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4QOG · 1.4 Å · ligand Melatonin (ML1). Experimental structure, not a prediction.
What the evidence adds up to
In CSE knockout mice, a model lacking the enzyme that produces hydrogen sulfide, the rate of gluconeogenesis was reduced. Giving NaHS, an H2S donor, reversed that reduction. Isolated hepatocytes from the knockout mice showed a smaller glycemic response to chemical activation of the cAMP/PKA and glucocorticoid pathways compared to wild-type cells. Inhibitors of PKA or the glucocorticoid receptor reduced H2S-stimulated glucose production in both types of hepatocytes. Exogenous H2S increased S-sulfhydration of gluconeogenic enzymes and PGC-1α, raising their activity, and knockdown of PGC-1α lowered NaHS-induced glucose production. The study identifies three mechanisms by which endogenous H2S stimulates liver glucose production, but it is entirely in mice and isolated cells, not in humans with any glucose metabolism disease.
A single case report describes an 83-year-old diabetic woman whose glycaemia rose five days after starting escitalopram, despite good control on glibenclamide before the antidepressant. Her blood glucose returned to normal only after escitalopram was stopped, even though the antidiabetic dose was increased. The authors note that only one previous case of escitalopram-induced hyperglycaemia had been reported, and the mechanism remains unclear. This is a single patient observation, not a trial, and cannot be generalised.
A 2002 study of a 21-year-old man with brittle diabetes found that the therapist’s vacation and the announcement of hospital discharge were significant predictors of average blood glucose. Mood was a significant predictor of daily blood glucose variation. Blood glucose stabilised toward the end of inpatient psychotherapy. The authors call for further empirical studies to confirm the finding. The sample is one patient, and the design is observational.
A 2005 review notes that the genetics of common forms of abnormal glucose regulation, including type 2 diabetes, remain difficult to unravel because of clinical heterogeneity and complex gene-environment interactions. No specific gene or drug target is validated from that review. A 2020 journal issue description and a 2025 review of diabetic animal models add no new human data. What is still missing are large, controlled human trials that test whether manipulating H2S pathways affects glucose control in patients, prospective studies of antidepressant-induced glycaemic changes in diabetic populations, and adequately powered psychotherapy trials with standardised outcome measures. Patient stratification by genetic or metabolic subtype is absent from all these reports.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Antioxidants and Redox Signaling · 2015 · 63 citations
Decreased Gluconeogenesis in the Absence of Cystathionine Gamma-Lyase and the Underlying Mechanisms
AbstractAIMS: To investigate the regulation of hepatic glucose production by cystathionine γ-lyase (CSE)-generated hydrogen sulfide (H2S) in hepatic glucose production under physiological conditions. RESULTS: We found that CSE knockout (KO) mice had a reduced rate of gluconeogenesis, which was reversed by administration of NaHS (an H2S donor) (i.p.). Interestingly, isolated CSE KO hepatocytes exhibited a reduced glycemic response to chemical-induced activation of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid pathways compared with wild-type (WT) hepatocytes. Treatment with the inhibitors for PKA (KT5720) or glucocorticoid receptor (GR) (RU-486) significantly reduced H2S-stimulated glucose production from both WT and CSE KO mouse hepatocytes. NaHS treatment upregulated the protein levels of key gluconeogenic transcription factors, such as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and CCAAT-enhancer-binding protein-β (C/EBP-β). Moreover, exogenous H2S augmented the S-sulfhydration of the rate-limiting gluconeogenic enzymes and PGC-1α and increased their activities, which were lower in untreated CSE KO hepatocytes. Finally, knockdown of PGC-1α, but not C/EBP-β, significantly decreased NaHS-induced glucose production from the primary hepatocytes. INNOVATION: This study demonstrates the stimulatory effect of endogenous H2S on liver glucose production and reveals three underlying mechanisms; that is, H2S upregulates the expression levels of PGC-1α and phosphoenolpyruvate carboxykinase via the GR pathway; H2S upregulates the expression level of PGC-1α through the activation of the cAMP/PKA pathway as well as PGC-1α activity via S-sulfhydration; and H2S upregulates the expression and the activities (by S-sulfhydration) of glucose-6-phosphatase and fructose-1,6-bisphosphatase. CONCLUSION: This study may offer clues for the homeostatic regulation of glucose metabolism under physiological conditions and its dysregulation in metabolic syndrome.
Advanced Biomedical Research · 2014 · 39 citations · open access
Effects of melatonin on biochemical factors and food and water consumption in diabetic rats
AbstractBACKGROUND: Diabetic neuropathy is one of the serious problems due to microvessel vasculopathy in diabetes. It has been reported that hyperglycemia and hypertriglyceridemia are the underlying mechanisms in inducing and progression of diabetic neuropathy. The aim of the present study was to investigate the effects of melatonin on serum glucose and lipid levels, as well as food consumption and water intake in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Eighty male Wistar rats were randomly assigned to six groups including; normal control group, diabetic control group and 4 diabetic experimental groups that received melatonin intraperitoneally at doses of 2.5, 5, 10, and 20 mg/kg at the end of sixth week after verification of neuropathy by means of evaluation of sciatic nerve conduction velocity (MNCV), for two weeks. Blood glucose and lipid levels, body weight, the amounts of food consumption, and water intake were determined in all groups at weeks 0 (before diabetes induction), 3, 6, and at the end of eighth week. RESULTS: Treatment with melatonin reduced significantly the serum glucose (P < 0.001) and triglyceride (P < 0.05) levels, food consumption (P < 0.001), and water intake (P < 0.001) in diabetic rats at the end of eighth week. However, melatonin had no significant effect on body weight of diabetic animals. CONCLUSIONS: Treatment with melatonin could improve several signs of diabetes, including hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia. Therefore, melatonin may be used as an adjunct therapy in the treatment of diabetes.
Genetics of Common Forms of Glycaemia with Pathological Impact on Vascular Biology: Are We on the Right Track?
AbstractThe common forms of abnormal glucose regulation including type 2 diabetes and impaired glucose tolerance with pathological implications on vascular biology have a complex aetiology involving multiple cross-talks between genetic influences and important environmental modifying factors. Due to complexity of the genetics and the clinical heterogeneity of these disorders it has proven difficult to apply the same methodological approaches that have recently given insights into the molecular genetics of several single-gene disorders of glucose metabolism. This review gives some reflections on the challenges posed by the current hypotheses about the genetics of the widespread forms of abnormal glucose regulation as well as on the strengths and limitations of the methodological approaches applied to unravel the genetic components of common disorders. Also, we review recent progress in relation to a model for the pathogenesis of the various stages of abnormal glucose regulation based on the concepts of thrifty genes of metabolism and pro-inflammation and genes responsible for the appearance of impaired pancreatic beta-cell function and insulin signalling under the pressure of a westernized environment.
The International Journal of Psychiatry in Medicine · 2013 · 5 citations
A Case Report on Escitalopram-Induced Hyperglycaemia in a Diabetic Patient
AbstractThe incidence of depression in diabetic patients is quite high; moreover, it has been suggested that the presence of depression itself may increase the risk of diabetes mellitus. Hence, it follows that the simultaneous use of antidiabetic and antidepressant drugs is common. Some clinical evidence indicates that selective serotonin re-uptake inhibitors (SSRIs) could be very useful in treating overweight patients, both with and without diabetes. However, recent deregulation of glucidic metabolism was tested in diabetic subjects treated with antidepressants. Several cases of hyperglycaemia and hypoglycaemia associated with other SSRIs have been published, whereas only one case of escitalopram inducing hyperglycaemia has been noted. The exact mechanism of glucose control impairment in patients taking SSRIs--escitalopram in particular--still remains unclear. We describe a diabetic 83-year-old woman with good glycaemic control (as evinced by glycaemic and glycosylated haemoglobin assay--HbA1c--values) before escitalopram initiation in response to therapy with glibenclamide. Escitalopram resulted in a significantly increased glycaemia values 5 days following administration. Glycaemia values returned to normality only after suspension of escitalopram, despite antidiabetic dosage increase. We report this case to draw attention to escitalopram as a possible cause of glycaemic control loss.
Zeitschrift für psychosomatische Medizin und Psychotherapie · 2002 · 4 citations
Der Einfluß von Trennungserfahrungen während stationärer Psychotherapie auf die Blutzuckerregulation eines Patienten mit Brittle Diabetes
AbstractOBJECTIVES: During the inpatient psychotherapy of a 21-year-old male patient with Brittle Diabetes, psychic reactions and changes of blood glucose after separation were studied. METHODS: The patient was interviewed using the Adult Attachment Interview (AAI). Specific attachment-related stress factors were elaborated. During the course of therapy, blood glucose, body symptoms and mood ratings were recorded daily and statistically evaluated by time series analysis. The statistical analysis allowed testing of critical instances (separation) and psychic determinants of blood glucose control. RESULTS: Significant predictors for the average blood glucose were as follows: the therapist's vacation (p < 0.02) and the announcement of discharge from the hospital (p < 0.01). A significant predictor for the daily blood glucose variation was mood (p < 0.01); the trend of the blood glucose variation was negative (p < 0.01). CONCLUSION: Toward the end of the treatment the blood glucose was stabilized. This result suggests the benefit of psychotherapy for these patients. Further empirical studies are necessary to confirm the findings.
Diabetes/Metabolism Research and Reviews · 2020 · 0 citations · open access
Issue Information
AbstractDiabetes/Metabolism Research and Reviews is an indispensable resource for clinicians and researchers working in the fields of diabetes, endocrinology, metabolism and obesity.Our reviews section provides the latest updates on clinical and basic scientific advances in key areas of diabetes, obesity and metabolism, important historical overviews, discussion of controversial issues and opinions from prominent researchers and clinicians.Original articles describing clinical studies, translational and basic research related to diabetes, obesity, metabolism, or closely related metabolic disorders are welcome, as are articles concerned with treatment and management of issues related to patient care.
Zenodo (CERN European Organization for Nuclear Research) · 2025 · 0 citations · open access
EXPERIMENTAL DIABETIC ANIMAL MODELS FOR STUDYING DIABETES
AbstractDiabetes is a metabolic disorder that occurs due to decreased insulin levels and increased blood sugar levels. The disease is chronic and often has a risk of exacerbation. Conditions caused by diabetes can be fatal (hyperglycemic and hypoglycemic coma). According to statistics, diabetes is the second most common metabolic disorder after obesity. Diabetes occurs due to a lack of insulin. This disease is characterized by metabolic disorders of proteins, carbohydrates and fats. Insulin promotes the breakdown, synthesis and use of glycogen in the liver, and prevents the breakdown of carbohydrate compounds. In the process of protein metabolism, insulin initiates the synthesis of proteins and nucleic acids, preventing protein breakdown. The effect of insulin on fat metabolism is that it increases the rate of glucose entry into hepatocytes, activates cellular energy processes, slows down the breakdown of fats and improves the synthesis of fatty acids.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
CLINICAL PHARMACOLOGY OF HYPOGLYCEMIC DRUGS
AbstractHypoglycemic drugs are used in the group of metabolic diseases with carbohydrate metabolism disorders, especially diabetes. Different drugs are used depending on the individual characteristics of this disease, the level of compensation and the presence of complications, which allows for individual therapy. Therefore, this article provides detailed information about the use of hypoglycemic drugs and their mechanism of action
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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