Increased fructose 2,6-bisphosphate in peripheral blood mononuclear cells of patients with diabetes

Fructose 2,6-bisphosphate (F2,6BP) is a powerful allosteric activator of 6-phosphofructo-1-kinase, which is the rate-limiting enzyme for glycolysis. Mitogenic stimulation of lymphocytes is related to an enhanced rate of glucose utilization and F2,6BP mediated activation of glycolysis. To determine the effect of hyperglycemia on intracellular glycolysis of lymphocytes, we measured intracellular F2,6BP content in peripheral blood mononuclear cells obtained from patients with diabetes and normal subjects. A total of 62 subjects participated in the present study. Venous blood samples were collected and peripheral blood mononuclear cells were separated by Ficoll gradients. Intracellular F2,6BP levels in peripheral blood mononuclear cells from normal control subjects were significantly lower than age-matched diabetic subjects. We observed a significant positive correlation between intracellular F2,6BP levels and long term glycemic control, as assessed by HbA1c. These data suggest that hyperglycemia increases intracellular F2,6BP in immune cells. These findings may help to clarify the impaired function in immune cells in patients with diabetes

HbA1c and telemedicine during COVID-19

Aims/Introduction: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine

Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype

Background: Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. Methodology and Principal Findings: When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid β-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. Conclusions: These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders

The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

Aim: Macrophage migration inhibitory factor (MIF) is known as a pro-inflammatory cytokine that regulates a broad spectrum of inflammatory reactions. MIF is expressed in vascular smooth muscle cells (VSMCs), and inhibition of the progression of atherosclerosis was observed in MIF-deficient atherosclerotic mice. However, the functional role of MIF in VSMCs has not been elucidated. The aim of this study was to investigate the role of MIF on the migration of VSMCs. Methods: Cultured rat A10 cells, derived from rat embryonic aortic smooth muscle cells, were stimulated with oxLDL, and the effect of MIF knockdown on oxLDL-mediated migration of A10 cells was analyzed. Results: Intracellular MIF content was significantly increased and a marked increase of MIF concent-ration was observed in the supernatant of A10 cells treated with oxLDL. The migration of A10 cells was significantly accelerated by the stimulation of recombinant MIF in a dose-dependent manner. Notably, knockdown of intracellular MIF by siRNA abolished oxLDL-induced migration of A10 cells. Conclusion: These findings suggest that MIF acts on the migration of VSMCs in an autocrine and paracrine fashion. MIF appears to be a novel target for the prevention of cardiovascular events.This is an open access article distributed under the Creative Commons Attribution-NonCommercial-ShareAlike license

Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is a benign disorder with heterozygous inactivating mutations in the calcium-sensing receptor (CASR) gene. The present study describes the identification and functional analysis of a novel CASR gene mutation leading to FHH. The proband is a 33-yr-old woman (Ca 11.0 mg/dL, intact-PTH 68 pg/mL, FECa 0.17 %). Leukocyte DNA was isolated in four family members and a novel heterozygous mutation (D190G, GAT>GGT) in exon 4 of CASR gene was identified by direct sequence analysis. The mutant CASR expression vector was constructed by mutagenesis procedure and its response to Ca2+ was characterized by transient transfection into human embryonic kidney (HEK) 293 cells and treatment with increasing extracellular Ca2+ concentrations. HEK cells didn't activate intracellular signaling (MAPK activation) in response to increases of extracellular Ca2+ concentrations when the mutant receptor was expressed normally at the cell surface. The novel heterozygous mutation (D190G) identified in the present study showed that the reduction of activity of CASR to extracellular Ca2+ caused FHH in patients and our study demonstrated the importance of Asp-190 participated in response to Ca2+ in CASR

Cluster-randomized trial to improve the quality of diabetes management: The study for the efficacy assessment of the standard diabetes manual (SEAS-DM)

Aims/Introduction: ‘The Standard Diabetes Manual’ has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. Materials and Methods: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster‐randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30‐min relevant seminar at the inception of the intervention. The primary end‐point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. Results: A total of 416 patients were enrolled by 36 PCPs. During the 1‐year follow‐up period, the proportion of PCPs who adhered to recommendation‐concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. Conclusions: Implementation of ‘The Standard Diabetes Manual’ potentially leads to an improved quality of diabetes management by PCPs

A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive diabetes-related antibodies

Wolfram syndrome is a rare, autosomal recessive disorder characterized by early-onset diabetes mellitus, optic atrophy and neurological and endocrinological abnormalities. A 47-year-old Japanese man with frequent severe hypoglycemic episodes was diagnosed as Wolfram syndrome based on clinical features and laboratory data. He had positive glutamic acid decarboxylase (GAD) and insulinoma-associated antigen-2 (IA-2) antibodies, both uncommon in this syndrome. Genetic analysis revealed that WFS1 gene of the patient has a homozygous 5 base pairs (AAGGC) insertion at position 1279 in exon 8, causing a frameshift at codon 371 leading to premature termination at codon 443