Folistatin and type 2 diabetes mellitus
Authors:
Patrik Valent; Andrej Dukát
Authors‘ workplace:
V. interná klinika LF UK a UNB, Nemocnica Ružinov, Bratislava
Published in:
Forum Diab 2024; 13(1): 47-50
Overview
Follistatin is a recently discovered hepatokine that binds and neutralizes members of transforming growth factor β family (TGFβ). It has significance in reproductive actions, intrauterine development, building and maintaining muscle mass during regeneration and fasting, nevertheless mainly in regulation of metabolic pathways. Its association with type 2 diabetes (T2D) was besides other studies confirmed by two cohort studies: Swedish during 19-year follow-up (n = 4 060) and Finnish during 4-year follow-up (n = 883). Both demonstrated its potential to be a new early predictive biomarker for T2D. In patients with diabetic cardiomyopathy showed up its protective effect with capability to regress cardial dysfunction and reduce myocardial fibrosis. Latest researches opens up the issue of therapeutical usage of follistatin in diabetes with its change of expression for improvement of glucose uptake and increased insulin sensivity in tissues.
Keywords:
type 2 diabetes mellitus – biomarker – follistatin – hepatokine
Sources
Lowe WL Jr, Bain JR. Prediction is very hard, especially about the future: new biomarkers for type 2 diabetes? Diabetes 2013; 62(5): 1384–1385. Dostupné z DOI: <http://dx.doi.org/10.2337/db13–0057>.
Laakso M. Biomarkers for type 2 diabetes. Mol Metab 2019; 27S(Suppl): S139-S146. Dostupné z DOI: <http://dx.doi.org/10.1016/j.molmet.2019.06.016>.
Ortiz-Martínez M, González-González M, Martagón AJ et al. Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus. Curr Diab Rep 2022; 22(3): 95–115. Dostupné z DOI: <http://dx.doi.org/10.1007/s11892–022–01453–4>.
Papachristou S, Popovic DS, Papanas N. Circulating follistatin as a novel biomarker of type 2 diabetes mellitus risk. Int J Diabetes Dev Ctries 023; 43: 779–780. Dostupné z DOI: <https://doi.org/10.1007/s13410–023–01181–9>.
Hiroyuki K. Subchapter 33C – Follistatin. In: Yoshio Takei Y, Hironori A, Tsutsui K (eds). Handbook of Hormones. Academic Press 2016: 298-e33C-2. ISBN 9780128010280. Dostupné z DOI: <https://doi.org/10.1016/B978–0-12–801028–0.00189–6>.
Phillips DJ, de Kretser DM. Follistatin: A Multifunctional Regulatory Protein. Front Neuroendocrinol 1998; 19(4): 287–322. Dostupné z DOI: <https://doi.org/10.1006/frne.1998.0169>.
Patel K. Follistatin. Int J Biochem Cell Biol 1998; 30(10): 1087–1093. Dostupné z DOI: <https://doi.org/10.1016/S1357–2725(98)00064–8>.
Hansen JS, Plomgaard P. Circulating follistatin in relation to energy metabolism. Mol Cell Endocrinol 2016; 433: 87–93. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mce.2016.06.002>.
Zhang YQ, Kanzaki M, Shibata H et al. Regulation of the expression of follistatin in rat hepatocytes. Biochim Biophys Acta 1997; 1354(3): 204–210. Dostupné z DOI: <http://dx.doi.org/10.1016/s0167–4781(97)00085–7>.
Perakakis N, Kokkinos A, Peradze N et. Follistatins in glucose regulation in healthy and obese individuals. Diabetes Obes Metab 2019; 21(3): 683–690. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.13572>.
Gonzalez-Gil AM, Elizondo-Montemayor L. The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review. Nutrients 2020; 12(6): 1899. Dostupné z DOI: <http://dx.doi.org/10.3390/nu12061899>.
Hansen JS, Rutti S, Arous C et al. Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio. J Clin Endocrinol Metab 2016; 101(2): 550–560. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2015–3668>.
Hansen J, Brandt C, Nielsen AR et al. Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine. Endocrinology 2011; 152(1): 164–71. Dostupné z DOI: <http://dx.doi.org/10.1210/en.2010–0868>. Erratum in: Endocrinology 2015; 156(3): 1200.
Gilson H, Schakman O, Kalista S et al. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. Am J Physiol Endocrinol Metab 2009; 297(1): E157-E164. Dostupné z DOI: <http://dx.doi.org/10.1152/ajpendo.00193.2009>.
Lee SJ, Lee YS, Zimmers TA et al. Regulation of muscle mass by follistatin and activins. Mol Endocrinol 2010; 24(10): 1998–2008. Dostupné z DOI: <http://dx.doi.org/10.1210/me.2010–0127>.
Perakakis N, Mougios V, Fatouros I et al. Physiology of Activins/Follistatins: Associations With Metabolic and Anthropometric Variables and Response to Exercise. J Clin Endocrinol Metab 2018; 103(10): 3890–3899. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2018–01056>.
Anastasilakis AD, Polyzos SA, Skouvaklidou EC et al. Circulating follistatin displays a day-night rhythm and is associated with muscle mass and circulating leptin levels in healthy, young humans. Metabolism 2016; 65(10): 1459–65. Dostupné z DOI: <http://dx.doi.org/10.1016/j.metabol.2016.07.002>.
Norman RJ, Milner CR, Groome NP et al. Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome. Hum Reprod 2001; 16(4): 668–672. Dostupné z DOI: <http://dx.doi.org/10.1093/humrep/16.4.668>.
Erickson GF, Chung DG, Sit A et al. Follistatin concentrations in follicular fluid of normal and polycystic ovaries. Hum Reprod 1995; 10(8): 2120–2124. Dostupné z DOI: <http://dx.doi.org/10.1093/oxfordjournals.humrep.a136246>.
Chen MJ, Chen HF, Chen SU et al. The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome. Fertil Steril 2009; 92(6): 2041–2044. Dostupné z DOI: <http://dx.doi.org/10.1016/j.fertnstert.2009.06.009>.
Teede H, Ng S, Hedger M et al. Follistatin and activins in polycystic ovary syndrome: relationship to metabolic and hormonal markers. Metabolism 2013; 62(10): 1394–1400. Dostupné z DOI: <http://dx.doi.org/10.1016/j.metabol.2013.05.003>.
Hansen J, Rinnov A, Krogh-Madsen R et al. Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low-grade inflammation. Diabetes Metab Res Rev 2013; 29(6): 463–472. Dostupné z DOI: <http://dx.doi.org/10.1002/dmrr.2415>.
Sylow L, Vind BF, Kruse R et al. Circulating Follistatin and Activin A and Their Regulation by Insulin in Obesity and Type 2 Diabetes. J Clin Endocrinol Metab 2020; 105(5): dgaa090. Dostupné z DOI: <http://dx.doi.org/10.1210/clinem/dgaa090>.
Hansen JS, Pedersen BK, Xu G et al. Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes. J Clin Endocrinol Metab 2016; 101(7): 2816–2825. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2016–1681>.
Tao R, Wang C, Stöhr O et al. Inactivating hepatic follistatin alleviates hyperglycemia. Nat Med 2018; 24(7): 1058–1069. Dostupné z DOI: <http://dx.doi.org/10.1038/s41591–018–0048–0>. Erratum in: Nat Med 2018; 24(10): 1628. Dostupné z DOI: <http://dx.doi.org/10.1038/s41591–018–0129–0>.
Han X, Møller LLV, De Groote E et al. Mechanisms involved in follistatin-induced hypertrophy and increased insulin action in skeletal muscle. J Cachexia Sarcopenia Muscle 2019; 10(6): 1241–1257. Dostupné z DOI: <http://dx.doi.org/10.1002/jcsm.12474>.
Davey JR, Estevez E, Thomson RE et al. Intravascular Follistatin gene delivery improves glycemic control in a mouse model of type 2 diabetes. FASEB J 2020; 34(4): 5697–5714. Dostupné z DOI: <http://dx.doi.org/10.1096/fj.201802059RRR>.
Tao R, Stöhr O, Wang C et al. Hepatic follistatin increases basal metabolic rate and attenuates diet-induced obesity during hepatic insulin resistance. Mol Metab 2023; 71: 101703. Dostupné z DOI: <http://dx.doi.org/10.1016/j.molmet.2023.101703>.
Wang Y, Yu K, Zhao C et al. Follistatin Attenuates Myocardial Fibrosis in Diabetic Cardiomyopathy via the TGF-β-Smad3 Pathway. Front Pharmacol 2021; 12: 683335. Dostupné z DOI: <http://dx.doi.org/10.3389/fphar.2021.683335>.
Wu C, Borné Y, Gao R et al. Elevated circulating follistatin associates with an increased risk of type 2 diabetes. Nat Commun 2021; 12(1): 6486. Dostupné z DOI: <http://dx.doi.org/10.1038/s41467–021–26536-w>.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Forum Diabetologicum
2024 Issue 1
Most read in this issue
- Folistatin and type 2 diabetes mellitus
- Long term protective effects of empagliflozine in whole spectrum of patients with type 2 diabetes mellitus from early stages of disease
- Telemedicine in outpatient diabetes practice
- Blood pressure and cardiovascular risk prediction in patients with diabetes mellitus: an introduction