Course of pancreatic beta cell destruction in prediabetic NOD mice: a histomorphometric evaluation.
The course of pancreatic beta cell destruction during the prediabetic period of autoimmune diabetic syndromes is not precisely known. We have analyzed the course of insulitis (n = 140) and the beta cell and lymphocytic volume densities by morphometric methods (n = 80) in NOD mice aged 6 to 45 weeks. In the absence of diabetes the mean beta cell density was only slightly reduced with age: 0.64 +/- 0.04% glandular tissue (mean SEM; n = 12) in 6 wk-old mice, 0.52 +/- 0.06% in 45 wk-old mice (n = 12; ns). However, a minority of pancreases were free of insulitis or showed isolated periinsulitis at the end of the 45-wk follow-up period. Invasive insulitis (i.e. mononuclear cells invading the islet area) was detected in 60-85% of mice from the 12th week on. In non overtly diabetic mice, beta cell density was reduced only when insulitis was invasive in more than 40% of islets: 0.30 +/- 0.03%, (n = 11) vs 0.59 +/- 0.04% (n = 34) in moderately invasive insulitis (p < 0.05). These mice had significant metabolic abnormalities. In diabetic mice, the beta cell density was markedly decreased: 0.02 +/- 0.01% (n = 7; p < 0.001). On the whole, a lymphocytic infiltrate affecting less than 50% of the islet volume was compatible with a normal beta cell density. Beyond this 50% lymphocytic infiltration threshold, beta cell density was tightly and negatively related to the lymphocytic volume density.(ABSTRACT TRUNCATED AT 250 WORDS)
Debussche
X
X
Service d'Endocrinologie, Hôpital Sud, Amiens, France.
Lormeau
B
B
Boitard
C
C
Toublanc
M
M
Assan
R
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005934:Glucagon / Q000032:analysis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000032:analysis / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D012737:Sex Factors
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon