Abdominal radiation and diabetes: one more piece in the puzzle

Oeffinger, Kevin C.; Sklar, Charles A.

doi:10.1016/s1470-2045(12)70340-6

Cited by 19 publications

(9 citation statements)

References 9 publications

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“…The downregulation of GCGa (p = 0.032) was also validated using qPCR (Figure 7). Similarly the upregulation of SREBF1 which is known to modulate insulin sensitivity [85] is in line with the literature showing that radiation exposure can lead to insulin resistance [86]. In addition, the upregulation of KLF7 might suggest a decrease in insulin secretion [87].…”

Section: Pathway Analysis Of Induced Torpor With Radiation Reveals Stress Response With Prosurvival Signalssupporting

confidence: 85%

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Cahill

Silveira

Renaud

et al. 2021

Cells

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The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.

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Section: Pathway Analysis Of Induced Torpor With Radiation Reveals Stress Response With Prosurvival Signalssupporting

confidence: 85%

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Cahill

Silveira

Renaud

et al. 2021

Cells

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“…One recent analysis of 2520 childhood solid tumor and lymphoma survivors suggested that diabetes risk plateaus at doses of 20–29 Gy to the pancreatic tail, while a subsequent study of Hodgkin lymphoma survivors demonstrated a linear radiation dose–response relationship without any such plateau . Both of these studies, as well as the prior analysis from the Childhood Cancer Survivor Study, found that the association between diabetes risk and pancreatic radiation was independent of body mass index (BMI), thus leading investigators to surmise that treatment‐related diabetes is secondary to β‐cell dysfunction, and not obesity …”

Section: Introductionmentioning

confidence: 99%

Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study

Friedman

Hilden

Moskowitz

et al. 2018

Pediatric Blood & Cancer

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“…Interestingly, they observed a four-fold increased risk of hyperparathyroidism, an observation that has not, to our knowledge, been previously reported. Also hidden amongst the details, but a topic of recent discussion, 5-7 was a 60% increased risk of diabetes. Similarly, it is notable that survivors from all 13 cancer groups had an overall elevated risk of developing an endocrinopathy.…”

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confidence: 99%