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EFFECTS OF METFORMIN EXPOSURE DURING LACTATION ON MOUSE OFFSPRING METABOLIC HEALTH AND MATERNAL LACTATION CHARACTERISTICS
Author(s) -
Gregg Brigid,
Brill Joshua,
Botezatu Nathalie,
Smith Michelle R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.275.3
Subject(s) - lactation , metformin , offspring , endocrinology , weaning , medicine , pregnancy , mammary gland , insulin , biology , cancer , breast cancer , genetics
Background Metformin administration during pregnancy has become more accepted as clinical trials examining metformin use in pregnancy have expanded. New clinical trials are underway to investigate the potential benefits of metformin use during lactation. The importance of insulin signaling in milk secretion raises the possibility that an insulin sensitizer may have an impact on lactation output. We provide new data demonstrating that metformin exposure during lactation in a mouse model causes modifications to lactation leading to programming effects in the murine neonatal pancreas. Objective To establish how metformin administration during lactation in a rodent model impacts maternal lactation physiology and how this in turn effects pup metabolic health. Methods Metformin was delivered in drinking water to C57BL/6J mice at either a high or low dose from postnatal day 1 (P1) and continued throughout lactation (Met PN group). Animals were examined for pancreatic morphology at mid‐lactation and for metabolic health during young adulthood. Mothers were also examined for mammary gland characteristics during lactation and upon weaning. Results Dams given a lower aqueous dose of metformin from P1 showed an indication of increased milk output through estimated milk volume experiments. Metformin exposed pups also had increased body weight during the first 3 weeks of life. In a separate set of experiments, dams given a higher dose of metformin demonstrated decreased cleaved caspase‐3 by western blotting in mammary glands taken 2 days after weaning. Pups that nursed from the mothers that received a higher dose metformin showed increased b‐cell mass at postnatal day 11 (P11). Male offspring exhibited improved glucose tolerance test (GTT) at 2 months of age and an increase in glucose stimulated insulin secretion (GSIS) in vivo. Metformin exposed offspring body weight was lower in these offspring than control pups and remained so throughout the period of the experiment. Conclusions These findings suggest that metformin may have an impact on lactation output at lower doses and lead to a delay in involution of the mammary gland at the time of weaning at higher doses. These effects seem to result in long‐term programming of metabolic health in the offspring. These findings could support the use of metformin during lactation to augment milk output and the potential for this exposure to have beneficial effects on offspring metabolism. Support or Funding Information Amendt‐Heller Award for Newborn Research 1 K08 DK102526 01A1