Diabetes enhancement and increased islet antigen expression following neonatal injections of glucose and arginine in non-obese diabetic mice.
Modulation of beta-cell antigens at birth may affect the course of type I diabetes. Since the functional state of beta cells modulates antigen expression, we investigated whether neonatal injections of glucose and arginine (G-A) influence diabetes in non-obese diabetic (NOD) mice. Two groups of 90 mice (45 female, 45 male) were injected for the first 6 days of life with G-A or saline. To determine whether these injections influenced beta cell functional maturation, isolated islets were characterized according to insulin response to glucose or arginine. Modulation of antigens for islet-cell autoantibodies (ICA antigens) was analyzed by indirect immunofluorescence using ICA-positive human sera. Variations of pancreatic glutamic acid decarboxylase 67-kD (GAD 67) mRNA were evaluated by polymerase chain reaction (PCR), hybridization with a 32P-labeled probe, and densitometry of the autoradiographic bands. Female NOD mice treated with G-A displayed diabetes earlier and with a higher incidence (P < .01) than control mice, whereas the diabetes incidence was not statistically modified in G-A-treated male NOD mice. Insulitis was more severe (P < .03) in 2-month-old G-A-treated female NOD mice than in control mice, but was not statistically modified in male NOD mice. In both sexes, ICA antigens and GAD 67 mRNA were higher in G-A-treated mice than in control mice (P < .01). Islets isolated after neonatal G-A injections exhibited improved insulin sensitivity to both stimuli (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Immuno-Endocrinology, Institut National Recherche Agronomique/Ecole Nationale Vétérinaire de Nantes, University School of Medicine, France.
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O
Senecat
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Martignat
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A
Elmansour
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B
Charbonnel
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P
Saï
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology*; D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D016130:Immunophenotyping; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction; D012737:Sex Factors; D013154:Spleen / Q000473:pathology
D001323:Autoantibodies; D007328:Insulin; C024211:islet cell antibody; D001120:Arginine; D005968:Glutamate Decarboxylase; D005947:Glucose