Partial protection of 1 alpha-hydroxyvitamin D3 against the development of diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice.
1 alpha-Hydroxyvitamin D3 (1 alpha-OH-D3), a precursor of active vitamin D3, 1 alpha,25-dihydroxyvitamin D3, was tested in CD-1 mice for its in vivo effect against the development of diabetes induced by administering multiple low doses of streptozotocin (STZ). Daily intraperitoneal (IP) injections of 35 mg/kg body weight of STZ administered for 5 consecutive days to mice from 7 weeks of age induced a delayed-onset hyperglycemia, insulitis, and beta-cell degranulation in 26 of 28 mice. Only 12 of 29 mice developed diabetes when treated with simultaneous daily IP injections of 1 alpha-OH-D3 for 14 consecutive days, with diabetes defined as a plasma glucose level greater than 200 mg/dL. A daily dose of 0.3 micrograms/kg 1 alpha-OH-D3 also protected against the development of hyperglycemia in five of 13 mice, whereas 0.2 micrograms/kg 1 alpha-OH-D3 was ineffective, indicating a dose-related effect. Histological study showed that, among the 1 alpha-OH-D3-treated mice, the pancreatic islets of euglycemic mice showed neither massive islet infiltration nor beta-cell degranulation, whereas those of the hyperglycemic mice showed insulitis. However, when diabetes was chemically induced with a single high dose of STZ, the simultaneous administration of 1 alpha-OH-D3 to mice failed to protect against the development of hyperglycemia; all five mice so treated developed hyperglycemia. Their pancreatic islets did not show insulitis. Therefore, it is suggested that 1 alpha-OH-D3 may protect against the development of diabetes following administration of multiple low doses of STZ, probably via an immune mechanism.
Inaba
M
M
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Nishizawa
Y
Y
Song
K
K
Tanishita
H
H
Okuno
S
S
Miki
T
T
Morii
H
H
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D051379:Mice; D010195:Pancreatitis / Q000517:prevention & control; D013311:Streptozocin / Q000008:administration & dosage
D001786:Blood Glucose; D006887:Hydroxycholecalciferols; D013311:Streptozocin; C008088:alfacalcidol