BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.
Diabetes Mellitus, Type 2* ; Fasting ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Humans ; Hypoglycemia ; Insulin Glargine ; Insulin Lispro* ; Insulin* ; Korea ; Meals ; Metformin ; Obesity ; Prevalence ; Weight Gain

BACKGROUND: The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly (ADP-ribose) polymerase (PARP) is increased in ALS. METHOD: Twenty Spinal cord specimens were obtained at the autopsy of sALS patients (n=11) and age-matched controls with non-neurological diseases (n=9). RESULTS: Using western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased three-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with the controls. PARP-IR was increased in the pellet fraction of sALS homogenates compared with the control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. CONCLUSIONS: The present results demonstrate glial alterations in sALS tissue and support the role of glial alterations in sALS pathogenesis.
Amyotrophic Lateral Sclerosis* ; Astrocytes* ; Autopsy ; Chromatin ; DNA Damage ; Humans ; Membranes ; Motor Neurons* ; Oxidative Stress ; RNA, Messenger ; Spinal Cord*

Background and Objectives: The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells. Results: NLRP3 showed a high level of expression in nasal polyps than in the control group (p<0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (p<0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (p<0.05). Conclusion The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.