DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for exercise-induced hyperinsulinism — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleExercise-induced hyperinsulinism maps to a 1-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
No approved-drug candidate for exercise-induced hyperinsulinism is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
solute carrier family 16 member 1 (SLC16A1) — SLC16A1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet phenylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7CKO · 2.95 Å · ligand 7-[methyl-(phenylmethyl)amino]-2-oxidanylidene-chromene-3-carboxylic acid (G5L). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not address exercise-induced hyperinsulinism. They cover exercise effects on fatty liver disease, prolactin secretion, cachexia drug development, glucose production during energy deficit, and muscle hypertrophy with GABA and whey protein. None of these studies involve patients with exercise-induced hyperinsulinism or measure insulin levels in response to exercise in that population. No concrete numbers on survival, response rates, or sample sizes for exercise-induced hyperinsulinism appear in these abstracts.
The 2011 study on high protein diet and glucose production during exercise-induced energy deficit enrolled 19 men and found that a 1000 kcal per day deficit decreased glucose production, while additional dietary protein mitigated that effect. The 2006 bicarbonate study enrolled 7 male recreational athletes and found that bicarbonate infusion prevented the exercise-induced rise in serum prolactin, suggesting acidosis is a stimulus for that rise. The 2018 rat study found that exercise suppressed the MGAT1 pathway in fatty liver disease, with protein expression significantly lower in exercised rats than in both high-fat diet and dietary adjustment groups. The 2015 review on exercise mimetics for cachexia notes that no effective therapy is available and that exercise mimetics may have serious side effects. The 2016 study on GABA and whey protein enrolled 26 men and found that combined ingestion increased lean mass by 1340 grams versus 146 grams with whey protein alone over 12 weeks.
What is still missing for exercise-induced hyperinsulinism specifically: any clinical trial data, any patient stratification, any funding directed at this condition, and any study design that measures insulin response to exercise in affected individuals. The abstracts here are irrelevant to that disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of sport and health science/Journal of Sport and Health Science · 2018 · 30 citations · open access
AbstractPURPOSE: Monoacylglycerol O-acyltransferase 1 (MGAT1) is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). Thus, this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet (HFD)-induced obese rats. METHODS: Male Sprague-Dawley rats were fed an HFD containing 45% fat for 6 weeks. Upon confirmation that NAFLD had been induced in the obese animals, they were divided into HFD-fed groups provided with exercise (HFD + EXE) or without exercise (HFD) and a group given dietary adjustment (DA) only, for a further 6 weeks of intervention treatment. The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise. Lipid accumulation in the liver tissue was determined by Oil Red O staining. The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR, and their protein levels by western blot assay. RESULTS: Oil Red O staining showed that NAFLD was successfully induced by HFD-fed. The gene expression of MGAT1 was significantly lower in HFD + EXE than HFD. However, there was no significant difference between HFD + EXE and DA. The protein expression of MGAT1 was significantly lower in HFD + EXE than both HFD and DA. Messenger RNA and protein expression of other lipogenic genes were not different among groups. These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding; in part, this effect could be greater than DA. CONCLUSION: Our data suggest that exercise can improve NAFLD, which is probably due to suppression of MGAT1 pathway.
Medicine & Science in Sports & Exercise · 2006 · 28 citations
Bicarbonate Reduces Serum Prolactin Increase Induced by Exercise to Exhaustion
AbstractPURPOSE: The aim of the study was to examine the effect of acid-base status on serum prolactin (PRL) concentration postexercise. METHODS: Seven male recreational athletes participated in two experimental trials separated by 1 wk. In the respective trial, subjects received either a placebo infusion (normal isotonic saline) or an alkali infusion (isotonic sodium bicarbonate) before and during exercise. Venous and capillary blood samples were drawn at rest, immediately after a 10-min warm-up period, and after a maximal ramp test on a cycle ergometer, as well as at 3, 6, 10, and 15 min postexercise. RESULTS: Power output, HR, capillary blood lactate concentration, carbon dioxide pressure (PCO2), and partial oxygen pressure (PO2) did not differ between trials at any point in time. Capillary PO2 did not change from resting values, but a significant increase (P < 0.05) was found from the end of warm-up to 3 min of the recovery period. Exercise induced a significant (P < 0.01) decrease in capillary blood bicarbonate concentration (HCO3-), pH, base excess (BE), and PCO2 at exhaustion and during the recovery period. Significantly higher HCO3-, pH, and BE were found during bicarbonate infusion and postexercise in comparison with the placebo trial. Serum PRL concentration was significantly increased 3 min postexercise until the end of the placebo trial, whereas after bicarbonate infusion, serum PRL concentration did not change from values at rest. Significant (P < 0.01) differences between trials in serum PRL concentration were found 10 and 15 min postexercise. CONCLUSIONS: The present study suggests that acidosis is a stimulus for exercise-induced PRL secretion.
Expert Opinion on Investigational Drugs · 2015 · 11 citations · open access
Novel investigational drugs mimicking exercise for the treatment of cachexia
AbstractINTRODUCTION: Cachexia is a syndrome characterized by body weight loss, muscle wasting and metabolic abnormalities, that frequently complicates the management of people affected by chronic diseases. No effective therapy is actually available, although several drugs are under clinical evaluation. Altered energy metabolism markedly contributes to the pathogenesis of cachexia; it can be improved by exercise, which is able to both induce anabolism and inhibit catabolism. AREAS COVERED: This review focuses on exercise mimetics and their potential inclusion in combined protocols to treat cachexia. The authors pay with particular reference to the cancer-associated cachexia. EXPERT OPINION: Even though exercise improves muscle phenotype, most patients retain sedentary habits which are quite difficult to disrupt. Moreover, they frequently present with chronic fatigue and comorbidities that reduce exercise tolerance. For these reasons, drugs mimicking exercise could be beneficial to those who are unable to comply with the practice of physical activity. Since some exercise mimetics may exert serious side effects, further investigations should focus on treatments which maintain their effectiveness on muscle phenotype while remaining tolerable at the same time.
High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial
AbstractBACKGROUND: Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metabolism are mitigated by increased dietary protein. METHODS: Nineteen men ([mean ± SD] 23 ± 2 y, VO2peak 59 ± 5 ml·kg-1·min-1) were divided into three groups, two consuming moderate (MP; 0.9 g protein kg-1 d-1), and one high (HP; 1.8 g protein kg-1 d-1) protein diets (55% energy from carbohydrate) for 11 days. Following 4 days of energy balance (D1-4), energy expenditure was increased for 7 days (D5-12) in all groups. Energy intake was unchanged in two, creating a 1000 kcal d-1 deficit (DEF-MP, DEF-HP; n = 6, both groups), whereas energy balance was maintained in the third (BAL-MP, n = 7). Biochemical markers of substrate metabolism were measured during fasting rest on D4 and D12, as were GP and contribution of gluconeogenesis to endogenous glucose production (fgng) using 4-h primed, continuous infusions of [6,6-2H2]glucose (dilution-method) and [2-13C]glycerol (MIDA technique). Glycogen breakdown (GB) was derived from GP and fgng. RESULTS: Plasma β-hydroxybutyrate levels increased, and plasma glucose and insulin declined from D4 to D12, regardless of group. DEF-MP experienced decreased plasma GP from D4 to D12 ([mean change ± SD] 0.24 ± 0.24 mg·kg-1·min-1), due to reduced GB from D4 (1.40 ± 0.28 mg·kg-1·min-1) to D12 (1.16 ± 0.17 mg·kg-1·min-1), P < 0.05. Conversely, BAL-MP and DEF-HP sustained GP from D4 to D12 ([mean change ± SD] 0.1 ± 0.5 and 0.0 ± 0.2 mg·kg-1·min-1, respectively) by maintaining GB. CONCLUSION: Exercise-induced energy deficit decreased GP and additional dietary protein mitigated that effect.
Medicine & Science in Sports & Exercise · 2016 · 0 citations
Combined Oral Intake of GABA with Whey Protein Improves Lean Mass in Resistance-trained Men
AbstractGamma aminobutyric acid (GABA) is one of the amino acids and is an inhibitory neurotransmitter. Oral administration GABA reportedly elevates resting serum growth hormone (GH) concentrations. GH is an important regulator of body composition including muscle protein synthesis, although the effect of GABA on muscle anabolism is unclear. On the other hand, it is well known that ingestion of protein after exercise stimulates protein synthesis in skeletal muscles. In addition to post-exercise protein supplementation, the ingestion of GABA may have additive effect in training-induced muscle hypertrophy. PURPOSE: To examine the effect of oral administration of GABA combined with whey protein on muscular hypertrophy during progressive resistance training in men. METHODS: Twenty-six healthy male volunteers (26-48 yrs) were divided into one of two groups; whey protein (WP) group ingesting 10g of whey protein, or whey protein + GABA (WP+G) group ingesting 10g of whey protein and 100 mg of GABA every day for 12 weeks. Both groups were subjected to a resistance training twice a week in which they performed three sets of 12 repetitions at 60% of one-repetition maximum on the following exercises: leg press, leg extension, leg curl, chest press and pull down. Body composition was assessed by dual-energy X-ray absorptiometry at baseline and 12wk after the training period. Resting plasma GH concentration was assessed at baseline, 4, 8 and 12wk. RESULTS: In WP+G group, plasma GH level in resting state was elevated significantly at 4 and 8wk compared with week 0 (689 ± 203, 661 ± 199 vs. 264 ± 93 pg/mL, p<0.05 respectively). On the other hand, plasma GH level in WP group was elevated significantly only at 8wk as compared with baseline (589 ± 179 vs. 237 ± 86 pg/mL, p<0.05). After 12 wk, change in whole body lean mass was significantly higher in WP+G group compared to that in WP group (1340 ± 465 vs. 146 ± 218 g, p<0.05). CONCLUSIONS: Combined ingestion of GABA with whey protein increased lean mass more effectively than ingestion of whey protein alone in resistance-trained men. Therefore, dairy supplementation with GABA may be a useful addition to whey protein for augmenting exercise-induced muscle hypertrophy.
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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