Several epidemiological studies support the protective role of breastfeeding in reducing the risk for type 1 diabetes. Human breast milk is the perfect nutrition for infants and contains many complex proteins, lipids and carbohydrates. In this study, we examined the physiological effects of human milk-derived opioid peptides, β-casomorphins (BCM), and compared them with bovine-milk-derived opioid peptides on pancreatic hormone regulation and β-cell regeneration. Exposure of wild-type zebrafish embryos to 50 µg/ml of human BCM-5 and -7 from 3 days post fertilisation until 6 days post fertilisation resulted in an increased insulin domain of expression while exposure to bovine BCM-5 and -7 significantly reduced the insulin domain of expression as analysed by whole-mount in situ hybridisation. These changes may be accounted for by reduced insulin expression or β-cell number and were mitigated by the µ-opioid receptor antagonist, naloxone. The effect of BCM on β-cell regeneration was assessed following ablation of β-cells in Tg (ins: CFP-NTR) zebrafish from 3 days post fertilisation to 4 days post fertilisation, followed by exposure of bovine and human BCM-5 and -7 (50 µg/ml) from 4 days post fertilisation until 7 days post fertilisation. The regenerative capacity of β-cells was not impeded following exposure to human BCM-5 and -7, whereas the capacity of β-cells to regenerate following bovine BCM-5 and -7 exposure was reduced. Our data suggest that human BCM-5 and -7 may promote β-cell development and enable the regeneration of β-cells, while the bovine-milk-derived peptides, BCM-5 and -7, play an opposite role. These data may provide some biological explanation for the protective effect of breastfeeding on the development of type 1 diabetes.
Keywords: Bovine β-casomorphin; Human β-casomorphin; Pancreas; Regeneration; Type 1 diabetes; Zebrafish; β-cell.
© 2020. Published by The Company of Biologists Ltd.