Abstract

Sphingolipids are a diverse group of lipids with important roles in beta-cell biology regulating insulin folding and controlling apoptosis. Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA. Here we tested the effect of L-serine supplementation on autoimmune diabetes development and blood glucose homeostasis in female NOD mice. We found that continuous supplementation of L-serine reduces diabetes incidence and insulitis score. In addition, L-serine treated mice had an improved glucose tolerance test, reduced HOMA-IR, and reduced blood glucose levels. L-serine led to a small reduction in body weight accompanied by reduced food and water intake. L-serine had no effect on pancreatic sphingolipids as measured by mass spectrometry. The data thus suggests that L-serine could be used as a therapeutic supplement in the treatment of Type 1 Diabetes and to improve blood glucose homeostasis.

Highlights

  • Type 1 Diabetes is an autoimmune disease in which the insulin producing beta cells are either destroyed by autoreactive T cells or dysfunctional leading to insulin deficiency and hyperglycemia [1]

  • We tested the hypothesis that dietary supplementation of the sphingolipid precursor L-serine would be protective against autoimmune diabetes in NOD mice by regulating pancreas sphingolipid composition

  • We found that L-serine reduced diabetes incidence and reduced inflammation in pancreatic islets (Fig 1A–1C)

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Summary

Introduction

Type 1 Diabetes is an autoimmune disease in which the insulin producing beta cells are either destroyed by autoreactive T cells or dysfunctional leading to insulin deficiency and hyperglycemia [1]. The development of Type 1 Diabetes is influenced by several factors, including genetic susceptibility [2], and environmental factors such as diet, viruses, and microorganism [3]. The NOD mouse is the preferred animal model for studying autoimmune diabetes, as it develops diabetes spontaneously with similarities to human Type 1 Diabetes [6]. Numerous treatments are known to prevent or reverse autoimmune diabetes in NOD mice, these have not been successful in human trials [7]. Growing evidence suggest a key role for sphingolipids in the pathogenesis of Type 1 Diabetes [8,9,10].

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