2. Academic Validation
  3. Dietary or pharmacological inhibition of insulin-like growth factor-1 protects from renal ischemia-reperfusion injury in mice

Dietary or pharmacological inhibition of insulin-like growth factor-1 protects from renal ischemia-reperfusion injury in mice

  • iScience. 2024 Oct 28;27(12):111256. doi: 10.1016/j.isci.2024.111256.
Arnaud Lyon 1 2 3 4,  Thomas Agius 1 3 4,  Michael R Macarthur 5,  Kevin Kiesworo 1,  Louis Stavart 1 2,  Florent Allagnat 1,  Sarah J Mitchell 6,  Leonardo V Riella 4,  Korkut Uygun 3 4,  Heidi Yeh 3 4,  Sebastien Déglise 1,  Déla Golshayan 2,  Alban Longchamp 1 3 4
Affiliations

Affiliations

  • 1 Department of Vascular Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
  • 2 Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
  • 3 Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 4 Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 5 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
  • 6 Ludwig Princeton Branch, Princeton University, Princeton, NJ, USA.
PMID: 39759002 DOI: 10.1016/j.isci.2024.111256
Abstract

One-week protein restriction (PR) limits ischemia-reperfusion (IR) damages and improves metabolic fitness. Similarly, longer-term calory restriction results in increased lifespan, partly via reduced insulin-like growth factor (IGF)-1. However, the influence of short-term PR on IGF-1 and its impact on IR are unknown. PR was achieved in mice via one-week carbohydrate loading and/or through a low-protein diet. PR decreased IGF-1 circulating levels as well as renal and hepatic expression. Upon renal IR, serum IGF-1 positively correlated with renal dysfunction and tissular damages, independently of sex and age. Exogenous IGF-1 administration abrogated PR benefits during IR, while IGF-1 receptor inhibition with linsitinib was protective. IGF-1 was associated with a reduction in forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways previously demonstrated to improve IR resilience in various organs. These data support dietary or pharmacological reduction of IGF-1 signaling to mitigate IR injury prior to solid organ transplantation and beyond.

Keywords

Biochemistry; Biological sciences; Cellular physiology; Natural sciences; Pharmacology; Physiology.

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