The effect of spermidine on autoimmunity and beta cell function in NOD mice

Abstract

Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for β-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.

Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice

“…Next, in order to distinguish mice diagnosed at the beginning of the study from the ones diagnosed later or those that remained diabetic-free, we segregated mice into three groups (early T1D, late T1D, and no T1D) based on the age at diagnosis, as described in Supplementary Fig. 1b 21 , 22 . This approach revealed the absence of correlations between the precocity of T1D-diagnosis and insulin autoantibody levels.…”

Relationships and Mendelian Randomization of Gut Microbe-Derived Metabolites with Metabolic Syndrome Traits in the METSIM Cohort

“…Variations in polyamine levels have been associated with multiple diseases including stroke, inflammation, and diabetes [ 54 ]. We found significant positive associations between spermidine and insulin resistance and WHR, and an inverse association with HDL-C. A spermidine supplementation resulted in enhanced diabetes incidence in nonobese diabetic mice with an increased proportion of proinflammatory T-cells in pancreatic lymph nodes [ 55 ]. In a cross-sectional study with 4230 individuals, serum spermidine was positively associated with increased odds of obesity but reduced odds of an increase in BMI in a follow-up study [ 56 ].…”

Serum Metabolomics Reveals a Potential Benefit of Methionine in Type 1 Diabetes Patients with Poor Glycemic Control and High Glycemic Variability

“…In vivo, spermidine inhibited HbA1c and lipid peroxidation [ 28 ]. However, a recent study on the role of spermidine treatment in T1D pathogenesis found that daily oral spermidine treatment in NOD mice resulted in a higher diabetes incidence, organ-specific spermidine accumulation, elevated peripheral inflammation, and a lower proportion of suppressive Tregs [ 29 ]. Reportedly, spermidine is linked to diabetic complications.…”