Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects.
Ramanjaneya. Manjunath M; Bettahi. Ilham I; Jerobin. Jayakumar J; Chandra. Prem P; Abi Khalil. Charbel C; Skarulis. Monica M; Atkin. Stephen Lawrence SL; Abou-Samra. Abdul-Badi AB
Key Findings
- Serum humanin is significantly lower in diabetics versus healthy controls
- Humanin levels inversely correlate with age, HbA1c, glucose, triglycerides, ALT, and TG/HDL ratio
- HbA1c and ALT are independent predictors of circulating humanin
Practical Outcomes
- Low humanin appears to be a marker of poor glucose control and liver stress. While the study doesn’t test supplementation, it hints that boosting humanin (e.g., via peptide supplements) could be worth exploring for metabolic health, but more clinical trials are needed before adopting it as a protocol.
Summary
People with type 2 diabetes have lower levels of the mitochondrial peptide humanin, and the amount drops as blood sugar control gets worse. Humanin levels also link to liver enzymes and other metabolic markers, suggesting it reflects overall metabolic health.
Abstract
<b>Background:</b> Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects. <b>Subjects and Measurements:</b> In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (<i>n</i> = 68), pre-diabetes (<i>n</i> = 33), T2D less than (good control; <i>n</i> = 31), and greater than HbA1c 7% (poor control; <i>n</i> = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression. <b>Results:</b> Serum HN concentrations were lower in T2D (<i>p</i> < 0.0001) and negatively correlated with age (<i>p</i> < 0.0001), HbA1c (<i>p</i> < 0.0001), glucose (<i>p</i> < 0.0001), triglycerides (<i>p</i> < 0.003), ALT (<i>p</i> < 0.004), and TG/HDL ratio (<i>p</i> < 0.001). Circulating HN levels were positively correlated to cholesterol (<i>p</i> < 0.017), LDL (<i>p</i> < 0.001), and HDL (<i>p</i> < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (<i>p</i> < 0.007). Circulating MOTS-c positively correlated with BMI (<i>p</i> < 0.035), total cholesterol (<i>p</i> < 0.0001), and LDL (<i>p</i> < 0.001) and negatively correlated with age (<i>p</i> < 0.002), HbA1c (<i>p</i> < 0.001), and glucose (<i>p</i> < 0.002). Serum ADP concentrations were lower in T2D (<i>p</i> < 0.002) and negatively correlated with HbA1c (<i>p</i> < 0.001), weight (<i>p</i> < 0.032) TG (<i>p</i> < 0.0001), and ALT (<i>p</i> < 0.0001); and positively correlated with HDL (<i>p</i> < 0.0001) and HN (<i>p</i> < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c. <b>Conclusion:</b> The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide an additional evidence that mitochondrial dysfunction contributes to glycemic dysregulation and metabolic defects in T2D.
Study Information
pubmed
2019
2019-05-31T00:00:00.000Z
10.3389/fendo.2019.00331
83
59