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The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying FoxO1gene regulation are largely unknown. We have previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a key role in the transcriptional regulation of glucose-responsive genes, including some that are involved in FoxO1-mediated glucose metabolism. Here we investigated the impact of HMGA1 on FoxO1gene expression. FoxO1 protein and gene expression studies were performed by Western blot analysis combined with qRT-PCR of material from human cultured cells and EBV-transformed lymphoblasts, and from primary cultured hepatocytes from wild-type and Hmga1–/–mice. Reporter gene assays and chromatin immunoprecipitation for binding of HMGA1 to the endogenous FoxoO1locus were performed in cells overexpressing HMGA1 and in cells pretreated with siRNA targeting HMGA1. HMGA1 increased FoxO1 mRNA and protein expression in vitro, in cultured HepG2 and HEK-293 cells by binding FoxO1gene promoter, thereby activating FoxO1gene transcription. Forced expression of HMGA1 in primary cultured hepatocytes from Hmga1–/–mice and in EBV-transformed lymphoblasts from subjects with reduced expression of endogenous HMGA1 increased FoxO1 mRNA and protein levels. These findings may contribute to the understanding of FoxO1gene regulation and its role in metabolism.

The prevalence of type 2 diabetes mellitus has increased worldwide over the past three decades, as a consequence of the more westernized lifestyle, which is responsible for the increasing obesity rate in the modern adult’s life. Concomitant with this increase there has been a gradual rise in the overall prevalence of gestational diabetes mellitus, a condition that strongly predisposes to overt diabetes later in life. Many women with previous gestational diabetes mellitus show glucose intolerance in the early postpartum period. Although the best screening strategy for postpartum glucose intolerance is still debated, numerous evidences indicate that identification of these women at this time is of critical importance, as efforts to initiate early intensive lifestyle modification, including hypocaloric diet and physical activity, and to ameliorate the metabolic profile of these high-risk subjects can prevent or delay the onset of type 2 diabetes mellitus. Nevertheless, less than one fifth of women attend the scheduled postpartum screening following gestational diabetes mellitus and they are at increased risk to develop type 2 diabetes mellitus later in their lives. Unsatisfying results have also come from early intervention strategies and tools that have been developed during the last few years to help improving the rate of adherence to postpartum glycemic testing, thereby indicating that more effective strategies are needed to improve women’s participation in postpartum screening.

In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that influences fat deposition and blood sugar levels. To date, however, very few in vitro models have been developed to investigate, at the molecular levels, the relationship between glucose, insulin and osteocalcin. This study aims at covering this gap. We studied osteogenic differentiation, osteocalcingene expression, and osteblast-mediated insulin secretion, using cultured MG-63 human osteoblast-like cells that underwent glucotoxicity and insulin resistance. In addition, we investigated whether a correlation existed between hyperglycemia and/or insulin resistance and total osteocalcin serum concentrations in patients. While insulin and low glucose increased osteocalcingene expression, disruption of insulin signaling in MG-63 osteoblasts and high glucose concentration in cell culture medium decreased osteocalcingene transcription and reduced osteogenic differentiation. Concomitantly, insulin secretion was significantly impaired in rat INS-1 β-cells treated with conditioned medium from insulin resistant MG-63 cells or cells exposed to high glucose concentrations. Also, chronic hyperglycemia, but not insulin resistance, inversely correlated with circulating osteocalcin levels in patients. Our results further support the existence of an endocrine axis between bone, where osteocalcin is produced, and pancreatic β-cells, and add new insights into the molecular details of this relationship. These findings may contribute to the understanding of osteocalcin regulation and its role in metabolism.

Correction to: Endocrinehttps://doi.org/10.1007/s12020-017-1396-0 The article Insulin and osteocalcin: further evidence for a mutual cross-talk, written by Francesco L. Bilotta, Biagio Arcidiacono, Sebastiano Messineo, Marta Greco, Eusebio Chiefari, Domenico Britti, Tomoko Nakanishi, Daniela P. Foti, Antonio Brunetti, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 2 September 2017 without open access.