Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study.

Daniel Åberg,Christian Blomstrand,Katarina Jood,Jörgen Isgaard,Petra Redfors,N David Åberg,Christina Jern,Johan Svensson

doi:10.3390/life11060499

Abstract

Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56–3.49, and fully adjusted HR 1.64, 95% CI 1.02–2.61). In contrast, crude associations with poor functional outcome (mRS 3–6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.

Highlights

Insulin-like growth factor-I (IGF-I) and IGF-II promote growth, metabolism, regeneration, and repair mechanisms in the peripheral tissues and in the central nervous system (CNS) [1,2]
We evaluated whether s-IGFII was associated with all-cause mortality by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analysis comparing the lowest quintile of s-IGF-II with that in the merged group of the four higher s-IGF-II quintiles
Serum IGF-II was higher in ischemic stroke (IS) cases both in the acute phase and after 3 months compared to controls (p < 0.05 and p < 0.01, respectively), there was no significant poststroke difference between the acute and 3-month s-IGF-II levels

Summary

Introduction

Insulin-like growth factor-I (IGF-I) and IGF-II promote growth, metabolism, regeneration, and repair mechanisms in the peripheral tissues and in the central nervous system (CNS) [1,2]. IGF-I and IGF-II are mainly produced in the liver [3], but there is production in other tissues including the CNS, most prominently in neurons [4,5]. The IGF2R targets acid hydrolases and IGF-II to lysosomes [8,9]. The IGF2R can recruit G proteins, thereby activating a cascade involving protein kinase C (PKC) and phospholipase C [8,10], which is distinct from that of the typical IGF-I signaling

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Discussion

Conclusion