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Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

ABSTRACT: In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD⁺) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD⁺ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).

SUBMITTER: Yoshino M

PROVIDER: S-EPMC8550608 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

Yoshino Mihoko M Yoshino Jun J Kayser Brandon D BD Patti Gary J GJ Franczyk Michael P MP Mills Kathryn F KF Sindelar Miriam M Pietka Terri T Patterson Bruce W BW Imai Shin-Ichiro SI Klein Samuel S

Science (New York, N.Y.) 20210422 6547

In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD<sup>+</sup>) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD<sup>+</sup> biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated gluc ...[more]

PMID: 33888596

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Project description:Aims/introductionPostmenopausal women receive bisphosphonates for osteoporosis treatment. The effect of these medications on developing diabetes mellitus in prediabetic patients is yet to be investigated. We aimed to determine the effect of alendronate on plasma glucose, insulin indices of postmenopausal women with prediabetes and osteopenia.Materials and methodsThe present triple-blind randomized controlled clinical trial included 60 postmenopausal women, aged 45-60 years. All patients were vitamin D sufficient. They were randomly enrolled in intervention (70 mg/week alendronate for 12 weeks) and control (placebo tablet per week for 12 weeks) groups. The morning 8-h fasting blood samples were collected at the baseline and follow-up visits to measure the fasting plasma glucose (mg/dL), insulin and hemoglobin A1c (HbA1c). Plasma glucose and insulin concentration were measured 30, 60 and 120 min after the glucose tolerance test. The Matsuda Index, homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the area under the curves of glucose and insulin were calculated.ResultsThe mean (standard deviation) fasting plasma glucose (102.43 [1.46] mg/dL vs 94.23 [1.17] mg/dL, P = 0.001), 120-min insulin concentration (101.86 [15.70] mU/L vs 72.60 [11.36] mU/L, P = 0.026), HbA1c (5.60 [0.06]% vs 5.40 [0.05]%, P = 0.001), homeostasis model assessment of insulin resistance (3.57 [0.45] vs 2.62 [0.24], P = 0.021) and Matsuda Index (7.7 [0.41] vs 9.2 [0.4], P = 0.001) significantly improved in the alendronate-treated group. There were more statistically significant reductions in fasting plasma glucose (-8.2 [8.63] mg/dL vs -2.5 [14.26] mg/dL, P = 0.002) and HbA1c (-0.2 [0.23]% vs -0.09 [0.26]%, P = 0.015) observed in the alendronate-treated group than the placebo group during the study course, respectively.ConclusionsAdministration of 70 mg/week alendronate improves fasting plasma glucose, HbA1c and insulin indices in postmenopausal women.

Dataset Information

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

Publications

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

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