The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.

BackgroundSTAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, whereas an activating STAT3 mutation has been linked to impaired β-cell function.MethodsThe role of STAT3 in β-cell neogenesis, induced by the exogenous expression of Pdx1, Neurog3, and Mafa, was analyzed in vitro and in vivo.FindingsThe expression of phosphorylated STAT3 (pSTAT3) was induced in both Pdx1-expressing and Mafa-expressing cells, but most of the induced β cells were negative for pSTAT3. The suppression of STAT3 signaling, together with exogenously expressed Pdx1, Neurog3, and Mafa, significantly increased the number of reprogrammed β cells in vitro and in vivo, enhanced the formation of islet-like clusters in mice, and ameliorated hyperglycemia in diabetic mice.InterpretationThese findings suggest that STAT3 inhibition promotes cellular reprogramming into β-like cells, orchestrated by defined transcription factors, which may lead to the establishment of cell therapies for curing diabetes.FundJSPS, MEXT, Takeda Science Foundation, Suzuken Memorial Foundation, Astellas Foundation for Research on Metabolic Disorders, Novo Nordisk, Eli Lilly, MSD, Life Scan, Novartis, and Takeda.

pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While β-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. the increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust downregulation of cell cycle-related genes 1 day after parturition, and the reupregulation of serotonin metabolism-related genes at postpartum day 7. Serotonin synthesis was activated only in lactating females, accompanied by increased β-cell mass. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.

ContextAccurate glucagon level measurements are necessary for investigation of mechanisms for postprandial hyperglycemia in type 2 diabetes.ObjectiveTo evaluate the accuracy of postprandial glucagon level measurements using a sandwich ELISA vs a recently established liquid chromatography-high resolution mass spectrometry (LC-HRMS) method in type 2 diabetes mellitus.Design and ParticipantsTwenty patients with type 2 diabetes treated with insulin underwent a meal test before and after administration of the dipeptidyl peptidase-4 inhibitor anagliptin for 4 weeks. Blood samples were taken serially after the meal, and glucagon levels were measured using both ELISA and LC-HRMS. We compared the change from baseline to 4 weeks (Δ0–4W) using the area under the curve for plasma glucagon during the meal test [area under the curve (AUC)0–3h] measured using ELISA and LC-HRMS.ResultsELISA-based glucagon AUC0–3h was higher than LC-HRMS–based AUC0–3h at baseline and 4 weeks. However, differences in Δ0–4W-AUC0–3h measured using ELISA and LC-HRMS were not statistically significant. Additionally, Δ0–4W-AUC0–3h measured using ELISA and LC-HRMS were strongly correlated (r = 0.87, P < 0.001).ConclusionsPlasma glucagon levels during a meal test in patients with type 2 diabetes measured using ELISA were consistently higher than those measured using LC-HRMS. However, given that the changes in glucagon levels measured using ELISA before and after dipeptidyl peptidase-4 inhibitor therapy were similar to those based on LC-HRMS, this ELISA seems to be useful for evaluating the effect of the drug interventions on postprandial glucagon levels.

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