Shuichi Okada

This article has been peer reviewed and published immediately upon acceptance. It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited.

Background: Transient high-glucose exposure induces Erk2 phosphorylation and cell proliferation in human coronary artery endothelial cells (HCAEC), but the upstream mechanisms remain unclear.Methods and Results: HCAEC were exposed to 183 mg/dL L-glucose or D-glucose for 1 h followed by 23 h in a glucose-free medium. Transient high D-glucose decreased miR-138 levels, increased Giα2 protein levels, inactivated Rap1, and activated Ras, leading to Erk2 activation.Conclusions: Transient high D-glucose exposure activates Erk2 via the miRNA-138/Giα2/Rap1/Ras signaling axis, suggesting a potential therapeutic target for atherosclerosis.

Hyperthyroidism is known to increase basal metabolism and glucose uptake in the skeletal muscles while promoting gluconeogenesis in the liver. However, the specific mechanism underlying thyroid hormone-induced postprandial hyperglycemia remains unclear. This study explored the influence of thyroid hormones on sodium/glucose cotransporter 1 (SGLT1) expression in the small intestine and their impact on postprandial glucose metabolism. Specifically, we examined the distribution of thyroid hormone receptors in the small intestine and the subsequent effect of thyroid hormones on SGLT1 expression using rat and genetically modified mouse models. Our results demonstrated a significant upregulation of SGLT1 in the distal small intestine following T4 treatment, which corresponded with the enhanced postprandial glucose levels after oral glucose administration but not intraperitoneal administration. Furthermore, in TRβΔ337T knock-in mice that exhibited resistance to thyroid hormones, we observed increased SGLT1 expression and postprandial hyperglycemia, reinforcing our findings in rats. These findings suggest that thyroid hormones enhance glucose absorption in the small intestine via SGLT1, contributing to postprandial hyperglycemia. This study elucidates a previously unexplored aspect of thyroid hormone physiology and highlights the regulatory role of thyroid hormones in SGLT1 expression, offering potential therapeutic avenues for managing postprandial hyperglycemia in patients with diabetes.

Clinical Diabetology is a bimonthly, open access journal of scientific and educational profile, which was created by combining the scientific assumptions of Experimental and Clinical Diabetology (Diabetologia Doświadczalna i Kliniczna)

Clinical Diabetology is a bimonthly, open access journal of scientific and educational profile, which was created by combining the scientific assumptions of Experimental and Clinical Diabetology (Diabetologia Doświadczalna i Kliniczna)

Tirzepatide, a dual glucagon-like peptide-1 receptor and gastric inhibitory peptide receptor agonist, is an effective treatment for type 2 diabetes mellitus and obesity, resulting in significant improvements in glycated hemoglobin levels and weight reduction. However, gastrointestinal side effects, including delayed gastric emptying, have been reported. Recently, a case of inadequate visualization during esophagogastroduodenoscopy due to substantial food residues in patients treated with tirzepatide has been reported. This study aims to report a patient who underwent a successful esophagogastroduodenoscopy following a 2-month discontinuation of tirzepatide. Previously, the same patient experienced incomplete esophagogastroduodenoscopies due to excessive food residues despite standard preparation. The findings of this study emphasize the challenges associated with the use of tirzepatide for upper gastrointestinal procedures and suggest that the discontinuation of the drug might be necessary to ensure optimal endoscopic evaluation.

Semaglutide is a well-designed drug with a special coating that allows for oral administration to patients with type 2 diabetes mellitus. However, patients taking oral semaglutide complain of its bitter taste. We therefore considered suggesting that patients take oral semaglutide with hot water. When the hot water temperature was increased to above 46.0°C but below 52.0°C, no bitter taste was perceived, with the daily mean interstitial glucose level remaining at the target range. Taking oral semaglutide with hot water helps reduce its bitter taste.

Objective: The aim of this clinical study was to discover a new factor affecting muscle strength and quality in patients with type 2 diabetes (T2D). Materials and methods: The relationship between muscle strength and quality and low-density lipoprotein cholesterol (LDL-C), random triglyceride (TG), and high-density lipoprotein cholesterol (HGL-C) levels were studied. Relative handgrip strength (RHGS) was used to evaluate muscular strength and quality. RHGS was calculated by dividing the absolute handgrip strength by body mass index (BMI). Using the stepwise method, multiple regression analysis was conducted and the linear correlation between variables was calculated by estimating Pearson correlation coefficient. Results: This study enrolled 68 patients with T2D. The majority of the participants were men, accounting for 71.5%. The median values of the measured parameters were as follows: age 67 years, physical activity level 10.1 METs/h/week, estimated glomerular filtration rate 57.0 mL/min/1.73 m2, systolic blood pressure 123.5 mmHg, diastolic blood pressure 69.0 mmHg, body weight 64.1 kg, body mass index 24.35 kg/m2, HbA1c level 7.4%, random TG level 139 mg/dL, HDL-C level 52.5 mg/dL, and T2D duration 16.0 years. RHGS was 1.47 ± 0.40 kg/BMI. RHGS was associated with LDL-C (r = 0.349) but was not correlated with random TG and HDL-C (r = 0.124 and r = 0.088, respectively). Conclusions: Patients with T2D with better muscle strength and quality demonstrated an increased LDL-C level. In patients with T2D, LDL-C may be a factor affecting muscle strength and quality. Keywords: relative handgrip strength low-density lipoprotein cholesterol type 2 diabetes