Correct Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program

Lévy, Jonathan; Matthews, David R.; Hermans, Michel P.

doi:10.2337/diacare.21.12.2191

Cited by 1,792 publications

(1,370 citation statements)

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“…2C). We used these measures to calculate insulin resistance and beta cell sensitivity using homeostasis model assessment (HOMA2‐IR) (Levy et al ., 1998). The HOMA2‐IR model was derived empirically from human insulin–glucose clamp data, but remains a useful surrogate measure of insulin resistance in mice (Mather, 2009).…”

Section: Resultsmentioning

confidence: 99%

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

et al. 2015

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SummaryInhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA‐approved drug rapamycin has been shown to promote lifespan and delay age‐related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long‐term prophylactic use of rapamycin as a therapy for age‐related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR‐containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA‐approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA‐approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs.

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Section: Resultsmentioning

confidence: 99%

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

et al. 2015

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“…Insulin resistance was estimated using the HOMA2 Calculator software available from the Oxford Centre for Diabetes, Endocrinology, and Metabolism Diabetes Trials Unit website as described (Levy, Matthews & Hermans, 1998). …”

Section: Methodsmentioning

confidence: 99%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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SummaryCalorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b 5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD +/sirtuin pathway. The results highlight the importance of these NAD + producers for the promotion of health and extended lifespan.

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“…Basal insulin sensitivity was estimated using the homeostasis model assessment (HOMA IS) 23 for fasting glucose (mmol/L) and insulin (μU/mL) concentrations. The calculations were made using the non‐linear HOMA Calculator 16.…”

Section: Methodsmentioning

confidence: 99%

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

Söder

Wernersson

Hagman

et al. 2016

Veterinary Internal Medicne

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BackgroundObese dogs risk poor life quality, creating a need for increased knowledge of metabolism in overweight dogs.ObjectivesInvestigate postprandial metabolic and hormonal responses to a high‐fat mixed‐meal in dogs and responses of lean versus overweight dogs.AnimalsTwenty‐eight healthy intact male Labrador Retrievers were included.MethodsProspective observational study. Twelve dogs were grouped as lean (body condition score (BCS 4–5), 10 as slightly overweight (BCS 6), and 6 as overweight (BCS 6.5–8) on a 9‐point scale. After an overnight fast, urine and blood samples were collected. Dogs were then fed a high‐fat mixed‐meal, and blood was collected hourly for 4 hours and urine after 3 hours.ResultsPostprandial concentrations of insulin and glucagon were increased at 1 hour (both P < 0.0001), triglycerides at 2 hours (P < 0.0001), and glucose at 3 hours (P = 0.004); and all remained increased throughout the feed‐challenge in all dogs. Postprandial urine cortisol/creatinine ratio was higher than fasting values (P = 0.001). Comparing between groups, there was an overall higher triglyceride response in overweight compared to lean (P = 0.001) and slightly overweight (P = 0.015) dogs. Overweight dogs also had higher fasting cortisol/creatinine ratio compared to lean dogs (P = 0.024).Conclusions and Clinical ImportancePostprandial responses of dogs to a high‐fat mixed‐meal were similar to those previously reported in people. The higher postprandial triglyceride response and fasting cortisol/creatinine ratio in the overweight dogs could be early signs of metabolic imbalance. Thus, although overweight dogs often appear healthy, metabolic alterations might be present.

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Correct Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program

Cited by 1,792 publications

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Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

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Correct Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program

Cited by 1,792 publications

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Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

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Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction