Transplacental exposure to bafilomycin disrupts pancreatic islet organogenesis and accelerates diabetes onset in NOD mice.
Bafilomycin, a plecomacrolide produced by plant-pathogenic Streptomyces, contaminates tuberous vegetables and has adverse effects on beta cells in adult mice. We therefore determined whether dietary bafilomycin influenced the progression of diabetes in the non-obese diabetic (NOD) mouse model of autoimmune Type 1 diabetes. Parent NOD mice were fed sub-toxic doses of bafilomycin in drinking water from conception until weaning, or various times after birth and blood glucose was monitored in the offspring. Pancreatic islets in neonatal offspring were examined histologically by quantitative morphometry and islet cell apoptosis was estimated by TUNEL assay. Exposure in utero to bafilomycin but not after birth significantly accelerated onset and increased the frequency of diabetes. In exposed mice, pancreatic islet organogenesis was disrupted, characterized by a striking increase in beta-cell mass and a shift in timing of the normal wave of neonatal islet cell apoptosis from 2 weeks to 4 weeks of age. We postulate that accelerated onset and increased incidence of diabetes later in life result from disruption of the normal turnover of beta cells in the neonatal pancreas. Since bafilomycin and related plecomacrolides contaminate Streptomyces-infected vegetables, dietary exposure during pregnancy could be an important and previously unsuspected environmental component of human Type 1 diabetes.
Hettiarachchi
K D
KD
Department of Biochemistry and Molecular Biology, Monash University, Building 13D, Wellington Road, Clayton, Victoria 3800, Australia.
Zimmet
P Z
PZ
Myers
M A
MA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000196:embryology / Q000209:etiology* / Q000473:pathology; D005260:Female; D005506:Food Contamination; D005516:Food Microbiology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000196:embryology* / Q000473:pathology; D018942:Macrolides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D016688:Mice, Inbred NOD; D011247:Pregnancy; D013302:Streptomyces / Q000472:pathogenicity; D014675:Vegetables / Q000382:microbiology
D018942:Macrolides; C052501:bafilomycin B1