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Aims/Introduction: Previous studies have reported that the glucagon-like peptide-1 receptor agonist (GLP-1RA) delays gastric emptying, and gastric emptying was assessed by the 13C breath test or paracetamol absorption technique. However, neither of them is clinically familiar in real-world clinical practice. The purpose of the present study was to investigate the association between GLP-1RA treatment and gastric residue in an esophagogastroduodenoscopy. Materials and Methods: This study was a matched pair case-control study. The study population consisted of 1,128 individuals with diabetes who had esophagogastroduodenoscopy at our clinic between July 2020 and June 2022. To account for differences in characteristics, such as age, sex, insulin treatment and glycated hemoglobin, we carried out a one-to-one nearest neighbor propensity score matching analysis between diabetes patients with and without GLP-1RA treatment. After matching, we compared the presence of gastric residue in an esophagogastroduodenoscopy by the McNemar test between patients with and without GLP-1RA treatment. Results: After the propensity score matching, we selected 205 pairs. In the propensity score-matched comparison, the proportion of gastric residue was statistically significantly higher in the GLP-1RA treatment group (0.49% vs 5.4%, P = 0.004). The details of GLP-1RA prescribed for the 11 patients with gastric residue were liraglutide once daily 1.8 mg (n = 2), dulaglutide once weekly 0.75 mg (n = 5), semaglutide once weekly 0.5 mg (n = 2) and semaglutide once weekly 1.0 mg (n = 2). Conclusion: GLP-1RA treatment is associated with gastric residue in an esophagogastroduodenoscopy in patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract  Bisphosphonate is an effective drug to reduce fracture risk in osteoporotic patients; however, factors affecting the efficacy of bisphosphonate treatment are not fully known, especially in Japanese patients. In the present study, we examined the relationships between an increase in lumbar spine bone mineral density (BMD) by bisphosphonates and several pretreatment parameters, including biochemical, bone/mineral, and body composition indices, in 85 postmenopausal osteoporotic patients treated with alendronate or risedronate. BMD increase was measured by dual-energy X-ray absorptiometry at the lumbar spine before and 2 years after treatment. BMD increase at the lumbar spine was observed as independent of age, height, weight, body mass index, and fat mass, although lean body mass seemed slightly related. On the other hand, fasting plasma glucose (FPG) levels were significantly and positively related to BMD increase at the lumbar spine. In multiple regression analysis, FPG levels were not significantly related to BMD increase at the lumbar spine when lean body mass was considered. As for bone/mineral parameters, BMD increase at the lumbar spine was not significantly related to serum levels of calcium, parathyroid hormone (PTH), and alkaline phosphatase or urinary levels of deoxypiridinoline and calcium excretion. As for BMD parameters, Z-scores of BMD at any site and bone geometry parameters obtained by forearm peripheral quantitative computed tomography were not significantly related to BMD increase at the lumbar spine. BMD increases at the lumbar spine were similar between groups with or without vertebral fractures. In conclusion, BMD increase at the lumbar spine by bisphosphonate treatment was not related to any pretreatment parameters, including body size, body composition, and bone/mineral metabolism in postmenopausal Japanese women with primary osteoporosis, although FPG correlated partly to BMD through lean body mass. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator–activated receptor (PPAR)-γ plays an important role in adipogenesis. However, the functions of PPAR-γ in differentiated adipocytes have remained unclear. The role of PPAR-γ in mature 3T3-L1 adipocytes was therefore investigated by overexpression of a dominant negative mutant of this protein (PPAR-γ-ΔC) that lacks the 16 COOH-terminal amino acids and that has been shown to prevent the thiazolidinedione-induced differentiation of 3T3-L1 cells into adipocytes. Overexpression of PPAR-γ-ΔC in mature 3T3-L1 adipocytes by adenovirus gene transfer resulted in a decrease in both cell size and intracellular triglyceride content, an increase in the extent of lipolysis, and a reduction in the rate of free fatty acid uptake. Furthermore, overexpression of this mutant reduced the abundance of mRNAs for several key enzymes that contribute to triglyceride and free fatty acid metabolism as well as the amounts of GLUT4, insulin receptor, insulin receptor substrate (IRS), and C/EBPα mRNAs. It also reduced both the concentration of IRS2 and the insulin-stimulated glucose uptake. These results suggest that PPAR-γ plays an important role in mature 3T3-L1 adipocytes at least in part by maintaining the expression of genes that confer the characteristics of mature adipocytes. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in feeding and body weight regulation. However, there is little genetic evidence that overexpression or knockout of the NPY gene leads to altered body weight regulation. Previously, we developed NPY-overexpressing mice by using the Thy-1 promoter, which restricts NPY expression strictly within neurons in the central nervous system, but we failed to observe the obese phenotype in the heterozygote. Here we report that in the homozygous mice, overexpression of NPY leads to an obese phenotype, but only after appropriate dietary exposure. NPY-overexpressing mice exhibited significantly increased body weight gain with transiently increased food intake after 50% sucrose- loaded diet, and later they developed hyperglycemia and hyperinsulinemia without altered glucose excursion during 1 year of our observation period. [ABSTRACT FROM AUTHOR]

Background. Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small protein with antioxidant property, on the development of diabetic nephropathy in streptozotocin-induced diabetic animals were investigated using TRX1 transgenic mice (TRX1-Tg). Methods. Eight-week-old male TRX1-Tg and wild-type mice littermates (WT) mice were treated either with streptozotocin (200 mg/kg) or vehicle alone. After 24 weeks of treatment, diabetic nephropathy and oxidative stress were assessed in these four groups of mice, by biochemical analyses of blood and urine, as well as by histological analyses of the kidneys. Results. Haemoglobin A1c (HbA1c) levels of diabetic TRX1-Tg were not significantly different from those of the diabetic WT. Nevertheless, an augmented urinary albumin excretion observed in diabetic WT was significantly diminished in diabetic TRX1-Tg. Histological study revealed that pathological changes such as mesangial matrix expansion and tubular injury were significantly prevented in diabetic TRX1-Tg accompanied by a reduced tendency of expression of transforming growth factor-β as compared with diabetic WT. In parallel, urinary excretion of 8-hydroxy-2′-deoxyguanosine and acrolein adduct and the immunostaining intensities of these markers in the kidney were significantly higher in diabetic WT compared with non-diabetic mice. The markers were significantly suppressed in diabetic TRX1-Tg, an indication of systemic and renal oxidative stress attenuation by TRX1 overexpression. Conclusion. These findings indicated the significant role of oxidative stress in the development of diabetic nephropathy and a potential inhibition of progression of nephropathy by TRX1. [ABSTRACT FROM AUTHOR]