Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice.
Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased in diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40% of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90% of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis and insulin secretion deficiency in CD-1 progeny.
Linn
T
T
Medical Clinic III, Justus Liebig University, Giessen, Germany.
Loewk
E
E
Schneider
K
K
Federlin
K
K
D000375:Aging / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D018149:Glucose Intolerance / Q000209:etiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010182:Pancreatic Diseases / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D012737:Sex Factors; D013045:Species Specificity
D007328:Insulin; D001120:Arginine; D005947:Glucose