Assessment of beta cell mass and oxidative peritoneal exudate cells in murine type 1 diabetes using adoptive transfer system.
Because it is controversial how the beta cell mass is reduced during the disease process in type 1 diabetes, we transferred splenocytes from Non-obese diabetic (NOD) to NOD-scid mice and evaluated the relation between the status of the pancreas in donors and the time taken to transfer diabetes to the recipients. We also evaluated the usefulness of assessment of the proportion of oxidative peritoneal exudate cells (PEC) as a novel marker of disease activity in this system. We examined the proportion of oxidative PEC, pancreatic insulin content and pancreatic histology in 16-18-week-old female NOD mice (donors), and transferred their splenocytes into 5-week-old female NOD-scid mice (recipients). After the onset of diabetes in NOD-scid recipients, we assessed the relation between insulin content (or severity of insulitis) of NOD donors and the time taken to transfer diabetes to NOD-scid recipients. The insulin content of "diabetes-prone" donors whose disease status was considered to be just before the onset of diabetes ("malignant" donors) was the same as that of diabetic mice, whereas the insulin content of "diabetes-prone" donors excluding "malignant" donors ("benign" donors) was the same as that of "non-diabetes-prone" donors. Because its proportion of oxidative PEC was inversely correlated with the severity of insulitis, we then evaluated the relation between the proportion of oxidative PEC and the time taken to transfer diabetes. "Malignant" donors had less proportion of oxidative PEC (< 10%), as compared to "benign" and "non-diabetes-prone" donors. These results suggest that a marked reduction of beta cell mass occurs at the very late prediabetic stage, and assessment of the proportion of oxidative PEC is useful to evaluate disease activity in type 1 diabetes.
Yamada
Satoru
S
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Irie
Junichiro
J
Shimada
Akira
A
Kodama
Keiichi
K
Morimoto
Jiro
J
Suzuki
Ryuji
R
Oikawa
Yoichi
Y
Saruta
Takao
T
D019264:Adoptive Transfer; D000818:Animals; D001202:Ascitic Fluid / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009929:Organ Size; D010084:Oxidation-Reduction; D011236:Prediabetic State / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D007328:Insulin