Top

Hormones

Published in:

01-12-2021 | Insulins | Original Article

Myostatin serum levels in children with type 1 diabetes mellitus

Authors: Alexandra Efthymiadou, Ioannis-Anargyros Vasilakis, Aristeidis Giannakopoulos, Dionisios Chrysis

Published in: Hormones | Issue 4/2021

Abstract

Purpose

Type 1 diabetes mellitus (T1DM) can cause several complications, among them myopathy, which can appear even in adolescents. This is of importance, since skeletal muscle is the largest of the insulin-sensitive tissues and thus plays a significant role in glucose homeostasis. A prime regulator of skeletal muscle mass is myostatin, a protein which has a negative role in skeletal muscle development but also in glucose homeostasis, causing insulin resistance. Since myopathy is a complication of T1DM and myostatin is a fundamental regulator of skeletal muscle and is also involved in glucose homeostasis, we investigated the serum levels of myostatin in children with T1DM.

Methods

We determined myostatin serum levels using ELISA in 87 children with T1DM aged 10.62 ± 3.94 years, and in 75 healthy children aged 10.46 ± 3.32 years old.

Results

Myοstatin was significantly elevated in T1DM compared to the healthy control children (23.60 ± 7.70 vs 16.74 ± 6.95 ng/ml, p < 0.0001). Myostatin was not correlated with body mass index (BMI) SD or hemoglobin A1c (HbA1c).

Conclusion

Children with T1DM have significantly higher serum levels of myostatin compared to healthy children of the same age and BMI SD. The elevated myostatin in T1DM could reflect impaired muscle function and/or glucose metabolism, or could represent a homeostatic mechanism.

Katz LD, Glickman MG, Rapoport S, Ferrannini E, DeFronzo RA (1983) Splanchnic and peripheral disposal of oral glucose in man. Diabetes 32:675–679. https://doi.org/10.2337/diab.32.7.675CrossRefPubMed

Baron AD, Brechtel G, Wallace P, Edelman SV (1988) Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol 255:E769–E774. https://doi.org/10.1152/ajpendo.1988.255.6.E769CrossRefPubMed

Krause MP, Riddell MC, Hawke TJ (2011) Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr Diabetes 12:345–364. https://doi.org/10.1111/j.1399-5448.2010.00699.xCrossRefPubMed

Andersen H, Gadeberg PC, Brock B, Jakobsen J (1997) Muscular atrophy in diabetic neuropathy: a stereological magnetic resonance imaging study. Diabetologia 40:1062–1069. https://doi.org/10.1007/s001250050788CrossRefPubMed

Andersen H, Schmitz O, Nielsen S (2005) Decreased isometric muscle strength after acute hyperglycaemia in Type 1 diabetic patients. Diabet Med 22:1401–1407. https://doi.org/10.1111/j.1464-5491.2005.01649.xCrossRefPubMed

Maratova K, Soucek O, Matyskova J et al (2018) Muscle functions and bone strength are impaired in adolescents with type 1 diabetes. Bone 106:22–27. https://doi.org/10.1016/j.bone.2017.10.005CrossRefPubMed

McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83–90. https://doi.org/10.1038/387083a0CrossRefPubMed

Grobet L, Pirottin D, Farnir F et al (2003) Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene. Genesis 35:227–238. https://doi.org/10.1002/gene.10188CrossRefPubMed

Reisz-Porszasz S, Bhasin S, Artaza JN et al (2003) Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab 285:E876–E888. https://doi.org/10.1152/ajpendo.00107.2003CrossRefPubMed

10.

Guo T, Bond ND, Jou W, Gavrilova O, Portas J, McPherron AC (2012) Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy. Diabetes 61:2414–2423. https://doi.org/10.2337/db11-0915CrossRefPubMedPubMedCentral

11.

Wilkes JJ, Lloyd DJ, Gekakis N (2009) Loss-of-function mutation in myostatin reduces tumor necrosis factor alpha production and protects liver against obesity-induced insulin resistance. Diabetes 58:1133–1143. https://doi.org/10.2337/db08-0245CrossRefPubMedPubMedCentral

12.

Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC (2009) Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS ONE 4:e4937. https://doi.org/10.1371/journal.pone.0004937CrossRefPubMedPubMedCentral

13.

Hittel DS, Berggren JR, Shearer J, Boyle K, Houmard JA (2009) Increased secretion and expression of myostatin in skeletal muscle from extremely obese women. Diabetes 58:30–38. https://doi.org/10.2337/db08-0943CrossRefPubMedPubMedCentral

14.

Garikipati DK, Rodgers BD (2012) Myostatin inhibits myosatellite cell proliferation and consequently activates differentiation: evidence for endocrine-regulated transcript processing. J Endocrinol 215:177–187. https://doi.org/10.1530/JOE-12-0260CrossRefPubMed

15.

Wang F, Liao Y, Li X, Ren C, Cheng C, Ren Y (2012) Increased circulating myostatin in patients with type 2 diabetes mellitus. J Huazhong Univ Sci Technolog Med Sci 32:534–539. https://doi.org/10.1007/s11596-012-0092-9CrossRefPubMed

16.

Amor M, Itariu BK, Moreno-Viedma V et al (2018) Serum myostatin is upregulated in obesity and correlates with insulin resistance in humans. Exp Clin Endocrinol Diabetes

17.

Tanaka M, Masuda S, Yamakage H et al (2018) Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients. Diabetes Res Clin Pract 142:195–202. https://doi.org/10.1016/j.diabres.2018.05.041CrossRefPubMed

18.

Ehehalt S, Schweizer R, Blumenstock G et al (2011) Investigation of myostatin serum levels before and after a 6-month lifestyle intervention program in obese children. Exp Clin Endocrinol Diabetes 119:238–242CrossRef

19.

Dial AG, Monaco CMF, Grafham GK et al (2020) Muscle and serum myostatin expression in type 1 diabetes. Physiol Rep 8:e14500. https://doi.org/10.14814/phy2.14500CrossRefPubMedPubMedCentral

20.

Yki-Jarvinen H, Koivisto VA (1986) Natural course of insulin resistance in type I diabetes. N Engl J Med 315:224–230. https://doi.org/10.1056/NEJM198607243150404CrossRefPubMed

21.

Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV (1986) Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 315:215–219. https://doi.org/10.1056/NEJM198607243150402CrossRefPubMed

22.

Donga E, Dekkers OM, Corssmit EP, Romijn JA (2015) Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis. Eur J Endocrinol 173:101–109. https://doi.org/10.1530/EJE-14-0911CrossRefPubMed

23.

Peltoniemi P, Yki-Jarvinen H, Oikonen V et al (2001) Resistance to exercise-induced increase in glucose uptake during hyperinsulinemia in insulin-resistant skeletal muscle of patients with type 1 diabetes. Diabetes 50:1371–1377. https://doi.org/10.2337/diabetes.50.6.1371CrossRefPubMed

24.

Nadeau KJ, Regensteiner JG, Bauer TA et al (2010) Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab 95:513–521. https://doi.org/10.1210/jc.2009-1756CrossRefPubMed

25.

Schauer IE, Snell-Bergeon JK, Bergman BC et al (2011) Insulin resistance, defective insulin-mediated fatty acid suppression, and coronary artery calcification in subjects with and without type 1 diabetes: the CACTI study. Diabetes 60:306–314. https://doi.org/10.2337/db10-0328CrossRefPubMed

26.

Cree-Green M, Stuppy JJ, Thurston J et al (2018) Youth with type 1 diabetes have adipose, hepatic, and peripheral insulin resistance. J Clin Endocrinol Metab 103:3647–3657. https://doi.org/10.1210/jc.2018-00433CrossRefPubMedPubMedCentral

27.

Bjornstad P, Schäfer M, Truong U et al (2018) Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus. Circulation 138:2895–2907. https://doi.org/10.1161/CIRCULATIONAHA.118.035525CrossRefPubMedPubMedCentral

28.

Monaco CMF, Hughes MC, Ramos SV et al (2018) Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes. Diabetologia 61:1411–1423. https://doi.org/10.1007/s00125-018-4602-6CrossRefPubMed

29.

Monaco CMF, Bellissimo CA, Hughes MC et al (2020) Sexual dimorphism in human skeletal muscle mitochondrial bioenergetics in response to type 1 diabetes. Am J Physiol Endocrinol Metab 318:E44–E51. https://doi.org/10.1152/ajpendo.00411.2019CrossRefPubMed

30.

Heyman E, Daussin F, Wieczorek V et al (2020) Muscle oxygen supply and use in type 1 diabetes, from ambient air to the mitochondrial respiratory chain: is there a limiting step? Diabetes Care 43:209–218. https://doi.org/10.2337/dc19-1125CrossRefPubMed

31.

Cree-Green M, Newcomer BR, Brown MS et al (2015) Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes 64:383–392. https://doi.org/10.2337/db14-0765CrossRefPubMed

32.

Assyov YS, Velikova TV, Kamenov ZA (2017) Myostatin and carbohydrate disturbances. Endocr Res 42:102–109. https://doi.org/10.1080/07435800.2016.1198802CrossRefPubMed

33.

Brandt C, Nielsen AR, Fischer CP, Hansen J, Pedersen BK, Plomgaard P (2012) Plasma and muscle myostatin in relation to type 2 diabetes. PLoS ONE 7:e37236. https://doi.org/10.1371/journal.pone.0037236CrossRefPubMedPubMedCentral

34.

Garcia-Fontana B, Reyes-Garcia R, Morales-Santana S et al (2016) Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Endocrine 52:54–62. https://doi.org/10.1007/s12020-015-0758-8CrossRefPubMed

35.

Coleman SK, Rebalka IA, D’Souza DM, Deodhare N, Desjardins EM, Hawke TJ (2016) Myostatin inhibition therapy for insulin-deficient type 1 diabetes. Sci Rep 6:32495. https://doi.org/10.1038/srep32495CrossRefPubMedPubMedCentral

36.

Jeong J, Conboy MJ, Conboy IM (2013) Pharmacological inhibition of myostatin/TGF-β receptor/pSmad3 signaling rescues muscle regenerative responses in mouse model of type 1 diabetes. Acta Pharmacol Sin 34:1052–1060. https://doi.org/10.1038/aps.2013.67CrossRefPubMedPubMedCentral

37.

Nuutila P, Knuuti J, Ruotsalainen U et al (1993) Insulin resistance is localized to skeletal but not heart muscle in type 1 diabetes. Am J Physiol 264:E756–E762. https://doi.org/10.1152/ajpendo.1993.264.5.E756CrossRefPubMed

38.

Kelley DE, Goodpaster B, Wing RR, Simoneau JA (1999) Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 277:E1130–E1141. https://doi.org/10.1152/ajpendo.1999.277.6.E1130CrossRefPubMed

39.

Zhang C, McFarlane C, Lokireddy S et al (2012) Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice. Diabetologia 55:183–193. https://doi.org/10.1007/s00125-011-2304-4CrossRefPubMed

40.

Bonala S, Lokireddy S, McFarlane C, Patnam S, Sharma M, Kambadur R (2014) Myostatin induces insulin resistance via Casitas B-lineage lymphoma b (Cblb)-mediated degradation of insulin receptor substrate 1 (IRS1) protein in response to high calorie diet intake. J Biol Chem 289:7654–7670. https://doi.org/10.1074/jbc.M113.529925CrossRefPubMedPubMedCentral

41.

Cleasby ME, Jarmin S, Eilers W et al (2014) Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal. Am J Physiol Endocrinol Metab 306:E814–E823. https://doi.org/10.1152/ajpendo.00586.2013CrossRefPubMedPubMedCentral

Title: Myostatin serum levels in children with type 1 diabetes mellitus
Authors: Alexandra Efthymiadou
Ioannis-Anargyros Vasilakis
Aristeidis Giannakopoulos
Dionisios Chrysis
Publication date: 01-12-2021
Publisher: Springer International Publishing
Keywords: Insulins
Insulins
Myopathy
Type 1 Diabetes
Published in: Hormones / Issue 4/2021
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-021-00317-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2021

Hypoglycemia due to PI3K/AKT/mTOR signaling pathway defects: two novel cases and review of the literature

Effect of sex hormones on human voice physiology: from childhood to senescence

The relationship of the built and food environments with the metabolic syndrome in the Athens metropolitan area: a sex-stratified spatial analysis in the context of the ATTICA epidemiological study

Vascular effects following intensification of glycemic control in poorly controlled patients with long-standing type 2 diabetes mellitus

Novel trends and concepts in the nutritional management of glycemia in type 2 diabetes mellitus—beyond dietary patterns: a narrative review

Subclinical thyroid dysfunction and major depressive disorder

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials