• Made available online as an Accepted Preprint 19 February 2009
  • Accepted Preprint first posted online on 19 February 2009

A low protein diet in early life delays the onset of diabetes in the non-obese diabetic mouse

  1. David J Hill1,2,4,5
  1. 1Lawson Health Research Institute, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of2Medicine3Microbiology and Immunology4Physiology and Pharmacology5Paediatrics, University of Western Ontario, London, Ontario, Canada N6A 5A5
  1. (Correspondence should be addressed to D J Hill; Email: dhill{at}lri.sjhc.london.on.ca)


Dietary insult in early life can affect the development and future function of the endocrine pancreas. We maintained pregnant non-obese diabetic (NOD) mice on a low protein (LP, 8% protein versus control, 20%) diet from conception until the weaning of pups at day 21. Serum insulin and pancreatic insulin content were reduced in LP-fed NOD offspring at 8 weeks, as were serum interferon γ and pancreatic tumor necrosis factor α, while the number of pancreatic islets demonstrating peri-insulitis, and the degree of invasiveness were reduced. To determine if LP caused early morphometric changes in the pancreas, we measured mean islet area at days 3 and 21. Mean islet size did not differ with diet, but by 8 weeks of age LP-fed NOD females exhibited a significantly reduced islet number and mean islet area, and a lower fractional area of pancreas occupied by both α- and β-cells than control-fed mice. The onset of diabetes was delayed in NOD mice of both genders fed LP diet. The mechanism is likely to involve both altered β-cell morphology and function and changes in cytotoxic cytokines.

  • Received in final form 7 February 2009
  • Accepted 19 February 2009
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