The pituitary gland is endocrine tissue composed of two distinct parts with different origins: the adenohypophysis (adenohypophyseal placode origin) and the neurohypophysis (neuroectoderm origin). Differentiation of endocrine cells in the pituitary gland leads to hormone synthesis, secretion into the capillary network, and transportation to target organs. In 1988, the discovery of the pituitary transcription factor PIT1 sparked research on endocrine cell differentiation. In the twenty-first century, the discovery that SOX2-positive stem/progenitor cells give rise to all types of pituitary endocrine cells advanced research on differentiation processes using diverse marker molecules. Lineage tracing using specific marker genes from early embryos revealed that during construction of the anterior pituitary from the adenohypophyseal placodal cells the developing anterior pituitary incorporates diverse cell types originating from the neural crest-derived and ectodermal-derived cells. Consequently, the postnatal anterior pituitary becomes a mosaic of terminally differentiated cells of different origin and with different life histories. It has also been revealed that most of the postnatal stem/progenitor cells form at least solid clusters in the parenchyma. Moreover, the classification and role of S100β-positive cells had been ambiguous, but now they are identified as a major component of postnatal stem/progenitor cells. This paper provides an updated overview of pituitary development.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (–0.3 SD vs. –1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was –0.2 SD in the cyclical menstruation group and –2.3 SD in the HRT group (p = 0.016). Spearman’s rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

This systematic review aimed to compare the influence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the efficacy and safety of elderly patients with type 2 diabetes and younger individuals. A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to September 2022. The summary standard means difference and odds ratios were calculated. Thirteen articles were included in the analysis. The incidence of adverse events (AEs) leading to discontinuation was higher in elderly patients (OR = 0.67, 95% CI 0.47 to 0.96, p = 0.028). However, no significant differences were observed in weight loss (SMD = 0.03, 95% CI –0.12 to 0.19, p = 0.686), HbA1c% (SMD = –0.02, 95% CI –0.11 to 0.08, p = 0.715), FBG levels (SMD = –0.03, 95% CI –0.11 to 0.06, p = 0.537), and the incidence of overall AEs (OR = 0.85, 95% CI 0.71 to 1.01, p = 0.072), serious AEs (OR = 0.68, 95% CI 0.45 to 1.04, p = 0.077), nausea (OR = 0.91, 95% CI 0.81 to 1.03, p = 0.140), vomiting (OR = 0.95, 95% CI 0.79 to 1.13, p = 0.532), diarrhea (OR = 0.86, 95% CI 0.72 to 1.02, p = 0.081), and hypoglycemia (OR = 1.22, 95% CI 0.90 to 1.65, p = 0.193). In conclusion, while certain AEs leading to discontinuation may be more prevalent in older patients, GLP-1RAs are effective for weight loss and lead to decreased glucose concentrations with a low rate of complications in elderly patients.

Diet therapy is one of the most important treatments for people with type 2 diabetes (T2D). However, dietary restrictions due to diet therapy may reduce quality of life (QOL). This cross-sectional study aimed to investigate the association between diabetes diet-related QOL and dietary fiber intake in 238 people with T2D. The Diabetes Diet-related Quality of Life–Revised version (DDRQOL-9-R) and the brief-type self-administered diet history questionnaire were used to evaluate diabetes diet-related QOL and nutritional intake, respectively. Higher scores of each DDRQOL-9-R subscale means greater satisfaction with diet, perceived merits of diet therapy, and lower burden of diet therapy, which indicates good QOL. The median scores for perceived merits of diet therapy, satisfaction with diet, and burden of diet therapy were 58.3 [41.7–75.0], 75.0 [66.7–91.7], and 66.7 [50.0–75.0] points, respectively. HbA1c levels in people with high perceived merits of diet therapy (7.3 [6.7–7.8] vs. 7.5 [7.1–8.2] %, p = 0.007) and people with high satisfaction with diet (7.3 [6.8–7.8] vs. 7.5 [7.1–8.4] %, p = 0.010) were lower than those without. Dietary fiber intake was higher in people with high perceived merits of diet therapy (11.6 [8.8–16.7] vs. 10.0 [7.9–13.8] g/day, p = 0.010), high satisfaction with diet (11.4 [8.8–16.1] vs. 9.7 [7.8–13.2] g/day, p = 0.007), and low burden of diet therapy (11.8 [8.7–16.5] vs. 9.7 [7.8–12.6] g/day, p = 0.004) than in those without. Dietary fiber intake was related to perceived merits of diet therapy (Odds ratio [OR]1.07 [95%CI: 1.00–1.15], p = 0.049), burden of diet therapy (OR 0.90 [95%CI: 0.82–0.98], p = 0.022), and satisfaction with diet (OR 1.18 [95%CI: 1.09–1.27], p < 0.001) after adjusting for covariates. Dietary fiber intake is associated with diabetes diet-related QOL in people with T2D.

Thioredoxin-interacting protein (TXNIP) plays an important role in glucose metabolism, and its expression is regulated by DNA methylation (DNAm). Although the association between TXNIP DNAm and type 2 diabetes mellitus has been demonstrated in studies with a cross-sectional design, prospective studies are needed. We therefore examined the association between TXNIP DNAm levels and longitudinal changes in glycemic traits by conducting a longitudinal study involving 169 subjects who underwent two health checkups in 2015 and 2019. We used a pyrosequencing assay to determine TXNIP DNAm levels in leukocytes (cg19693031). Logistic regression analyses were performed to assess the associations between dichotomized TXNIP DNAm levels and marked increases in glycemic traits. At four years, the TXNIP DNA hypomethylation group had a higher percentage of changes in fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared to those in the hypermethylation group. The adjusted odds ratios for FPG and HbA1c levels were significantly higher in the TXNIP DNA hypomethylation group than in the hypermethylation group. We found that TXNIP DNA hypomethylation at baseline was associated with a marked increase in glycemic traits. Leukocyte TXNIP DNAm status could potentially be used as an early biomarker for impaired glucose homeostasis.

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m²) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

To establish an easy way to perform volumetry of the thyroid gland using ultrasonography, we evaluated the accuracy of the products of the depth and width of the right thyroid lobe as indices of thyroid volume. The depth and width of both thyroid lobes were measured using ultrasonography before surgery in 193 patients with Graves’ disease. The products were compared with the weight of the thyroid obtained from operative records. We also evaluated the depth and width of the right thyroid lobe in 312 subjects who presented without any thyroid disease. The products of depth and width of the right and left lobes of patients with Graves’ disease correlated similarly well with the weight of the thyroid obtained from operative records (ρ = 0.896 for right, ρ = 0.886 for left, p < 0.0001). Because the right lobes were larger than the left lobes, the products of the depth and width of the right lobe were adopted as novel parameters for an easy volumetric approach. The relationship between the weight and the measurements of the right lobe was described using the following regression equation: weight (g) = [11.8 × depth (cm) × width (cm)] – 16.0. The products of the subjects without any thyroid diseases were distributed between 0.6 cm² and 4.4 cm², with a median of 2.0 cm². The upper limit of these values in these subjects was estimated to be 3.8 cm². This easy ultrasonographic volumetric technique makes it possible to perform a semi-quantitative assessment of thyroid volume and to differentiate diffuse goiter from normal-sized thyroids.

Interleukin 17A (IL-17A) is a key cytokine promoting osteoblast formation, which contributes to osteogenesis. IL-17A functions in autophagy inhibition within osteoblasts. Metallothionein-2 (MT-2), as an important reactive oxygen species (ROS)-scavenging molecule, prevents oxidative stress from damaging osteoblast formation. The relationship between IL-17A-regulated autophagy and MT-2 production under oxidative stress deserves further exploration. In this study, we first investigated the roles of IL-17A in osteoblastic differentiation and ROS production in osteoblast precursors in the presence of hydrogen peroxide (H₂O₂). Next, we explored the effects of IL-17A on autophagic activity and MT-2 protein expression in osteoblast precursors in the presence of H₂O₂. Ultimately, by using autophagic pharmacological agonist (rapamycin) and lentiviral transduction technology, the relationship between autophagy, IL-17A-regulated MT-2 protein expression and IL-17A-regulated ROS production was further elucidated. Our results showed that in the presence of H₂O₂, IL-17A promoted osteoblastic differentiation and inhibited ROS production. Moreover, in the presence of H₂O₂, IL-17A inhibited autophagic activity and promoted MT-2 protein expression in osteoblast precursors. Importantly, IL-17A-promoted MT-2 protein levels and -inhibited ROS production were reversed by autophagy activation with rapamycin. Furthermore, IL-17A-inhibited ROS production were blocked by MT-2 silencing. In conclusion, IL-17A promotes ROS clearance by inhibiting autophagic degradation of MT-2, thereby protecting osteoblast formation from oxidative stress.