Maternal caffeine exposure impairs insulin secretion by pancreatic β‐cells and increases the risk of type II diabetes mellitus in offspring

Abstract

Maternal caffeine exposure may be one of the causes for intrauterine growth retardation and low birth weight (LBW), and increased risk of type 2 diabetes mellitus (T2DM) in the adulthood has been associated with LBW. However, whether maternal caffeine exposure contributes to T2DM development of her offspring has not been fully investigated. We have investigated the influence of maternal caffeine exposure on glucose homeostasis in vivo and effects of long-term caffeine load on insulin secretion of β-cells. The intake of caffeine during gestation markedly decreases birth weight and postnatal body weight of the offspring. Serum insulin levels of adult offspring after oral glucose tolerance test (OGTT) were significantly lower in the caffeine group compared to the control, although plasma glucose levels were not significantly altered. Proteome analysis of pancreas of adult offspring identified 24 proteins that were differentially expressed between the caffeine and control groups, including proteins involved in energy metabolism. In a rat pancreatic β-cell line Rin-5f cells, caffeine downregulated expression of one of the proteins involved in insulin synthesis, P4hb, and there was reduced transcriptional expression of insulin. While basal insulin secretion of caffeine-treated cells was elevated, insulin secretion after glucose challenge in long-term caffeine-treated cells was significantly reduced, with increased apoptosis of β-cells. These results indicate that maternal caffeine exposure may result in potentially abnormal glucose homeostasis and increase the risk of T2DM in the offspring adulthood.