Newly weaned nonobese diabetic mice show heightened early diabetes sensitivity to multiple low doses of streptozotocin than nondiabetes-prone CD-1 mice: initial beta-cell damage a key trigger for type 1 diabetes?
OBJECTIVE
We determined if newly weaned female nonobese diabetic (NOD) mice show greater diabetes sensitivity to dose-adjusted regimens of multiple low doses of streptozotocin (Stz) than nondiabetes-prone CD-1 mice.


METHODS
Female NOD mice received 5 daily doses of Stz from day 21 (0, 5, 10, 15, 20, 30, and 40 mg/kg body weight) and CD-1 mice 20, 30, and 40 mg.


RESULTS
: Streptozotocin, at the 15-, 20-, 30-, and 40-mg dose, induced rapid diabetes in NOD mice. By day 100, 90% to 95% of NOD mice became diabetic after the 40- and 30-mg dose and 33% to 40% with the 15- and 20-mg dose. In comparison, only about 50% and 33% of CD-1 mice developed diabetes with the 40- and 30-mg dose, respectively, and 5.5% with the 20-mg dose. In NOD mice, the 20-mg dose also partially suppressed spontaneous diabetes. All diabetic mice displayed insulitis, variable immunostaining for insulin, and redistribution of glucagon and somatostatin cells. Glucose transporter-2 was markedly attenuated in selective beta cells.


CONCLUSIONS
Newly weaned female NOD mice show heightened early sensitivity to low doses of Stz than CD-1 mice. At diabetes, several beta cells remain and show variable immunostaining for insulin and an attenuated expression for glucose transporter-2. Specific low doses of Stz may also suppress spontaneous diabetes.
Reddy
Shiva
S
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Elliott
Robert B
RB
Chang
Mike
M
Hsu
Tim
T
Rodrigues
Jessica A
JA
Qiao
Linzi
L
Robinson
Elizabeth
E
D000367:Age Factors; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000473:pathology; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D012720:Severity of Illness Index; D013004:Somatostatin / Q000378:metabolism; D019864:Somatostatin-Secreting Cells / Q000473:pathology; D013045:Species Specificity; D013311:Streptozocin / Q000008:administration & dosage; D014886:Weaning
D051273:Glucose Transporter Type 2; D007328:Insulin; C495682:Slc2a2 protein, mouse; D013004:Somatostatin; D013311:Streptozocin; D005934:Glucagon