The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells / 당뇨병

BACKGROUND: The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression. METHODS: The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter. RESULTS: The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression. CONCLUSIONS: This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.

The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells / 당뇨병

BACKGROUND: The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in rat insulinoma cell line, INS-1 cell induces ER stress and whether ER stress decreases insulin gene expression. METHODS: The effect of 30 mM glucose on insulin expression and secretion in INS-1 cells was evaluated by Northern blot analysis and glucose-stimulated insulin secretion (GSIS). Cell viability was evaluated by XTT assay. The effect of 30 mM glucose on phosphorylation of eIF2alpha and CHOP expression, which are markers of ER stress were evaluated by Western blot analysis. RT-PCR analysis was performed to determine whether high glucose concentration induces XBP-1 splicing. To investigate whether ER stress decreases insulin gene expression, the effect of tunicamycin on insulin mRNA expression was evaluated by Northern blot analysis. RESULTS: The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulin mRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2alpha, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulin mRNA expression in a dose dependent manner. CONCLUSION: This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulin gene expression. Further studies about underlying molecular mechanism by which ER stress induces beta-cell dysfunction are needed.

Typhlitis due to propylthiouracil in a patient with hyperthyroidism / 대한내과학회지

Typhlitis is one of the most ominous complications in immunocompromised patients. Neutropenic enterocolitis or typhlitis is a clinical syndrome characterized by fever, diarrhea and abdominal pain that occurs in neutropenic patients. It has been reported as a complication of childhood leukemia, but is now known to occur in adults with solid malignancies, acquired immunodeficiency syndrome (AIDS) or bone marrow transplantation (BMT). The association of typhlitis and propylthiouracil has not been previously reported. We report a case of a 42-year-old female patient with typhlitis due to propylthiouracil patient with hyperthyroidism.

Clinical Outcomes of Early Vancomycin Administration before Identification of Methicillin-resistant Staphylococcus aureus in Patients with Nosocomial Pneumonia / 대한구급학회지

BACKGROUND: The aim of this study is to determine the clinical outcomes of early vancomycin administration before identification of methicillin-resistant Staphylococcus aureus (MRSA) in patients with nosocomial pneumonia on a ventilator. METHODS: We retrospectively reviewed patients with nosocomial pneumonia in a 20-bed medical ICU during a period of 2 years and 2 months. This study included 52 inpatients, who were admitted for more than 72 hr and had a new or progressive lung infiltrate plus at least two of the following three criteria for pneumonia: abnormal body temperature (>38oC or 10,000/mm3 or <3,000/mm3), and purulent bronchial secretions. All of the MRSA were identified in tracheal aspirates during mechanical ventilation. RESULTS: A total of 23 patients who received vancomycin prior to identification of MRSA exhibited a 28-day mortality rate of 60%, while 29 patients who received vancomycin after identification of MRSA showed a 28-day mortality rate of 40% (p=0.17). There was no statistically significant difference in severity index and routine laboratory findings between the two groups. CONCLUSIONS: Early vancomycin administration before identification of MRSA does not appear to affect the mortality rate for patients with nosocomial pneumonia.

Factors Associated with Early Death in Patients with Community-Acquired Pneumonia / 결핵및호흡기질환

BACKGROUND: Early death is an important problem associated with the management of community-acquired pneumonia. However, there is little information on the risk factors associated with it. The aim of this study was to identify the factors associated with early death in community-acquired pneumonia patients. METHODS: From January 1999 to July 2004, 1,487 adult patients with community-acquired pneumonia who were admitted to the pulmonary department via emergency center were examined. Early death was defined as those who died within 2 days of hospitalization. The clinical and laboratory aspects of the patients who died early (n=30) were compared with those of an age and gender matched control population (n=60) . RESULTS: In the early death group, respiratory rate, heart rate, and blood urea nitrogen (BUN) were significant higher (p<0.05 for all), while the arterial pH, systolic pressure, and PaO2 were significant lower (p<0.05 for all) than the control. The independent factor significantly associated with early death was tachypnea (OR, 7.049). CONCLUSION: The importance of an early clinical assessment in emergency center with community-acquired pneumonia needs to be emphasized in order to recognize patients at risk of early death.