Intact glucagon-like peptide-1 levels are not decreased in Japanese patients with type 2 diabetes.

Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes mellitus (T2DM). Recent studies, however, have not always supported this notion. Since Japanese patients with T2DM usually have severe impairment in the earlyphase of insulin secretion, the measurement of incretin secretions in Japanese T2DM patients would be useful for assessing the association between incretin levels and insulin secretion. We conducted an oral glucose tolerance test (75 g) (OGTT) and meal tolerance test (480 kcal) (MTT) for subjects with normal glucose tolerance (NGT, n=12), subjects with impaired glucose tolerance (IGT, n=7), and T2DM patients (n=21). The tests were carried out over 120-min study periods on separate occasions. Intact GLP-1, GIP, and dipeptidyl peptidase (DPP)-IV were measured by ELISA. T2DM exhibited an impaired early phase of insulin secretion and a reduction in glucagon suppression. There were no significant differences in GLP-1 or GIP levels at each sampling time among NGT, IGT, and T2DM after the ingestions; hence the incremental areas under the curve (IAUC) for the three groups were quite similar. The levels of DPP-IV, a limiting enzyme for the degradation of incretins, were comparable among the three groups. The GLP-1-IAUC was not correlated with IAUCs of insulin, C-peptide, or glucagon determined by the OGTT or the MTT. We concluded that intact GLP-1 levels are comparable between non-diabetics and T2DM, suggesting that impaired insulin secretion in Japanese T2DM is not attributable to defect in GLP-1 secretion.

Clinical characteristics of adrenal insufficiency as an immune-related adverse event in non-small-cell lung cancer.

Adrenal insufficiency (AI) is an immune-related adverse event of immune checkpoint inhibitors and on occasion could be serious. There have been few reports of clinical information regarding AI associated with anti-programmed cell death protein-1 (anti-PD-1) antibody in non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC treated with anti-PD-1 antibodies between December 2015 and October 2017 were identified from the medical records of our institution. We investigated the frequency, symptoms, test results, and treatment outcomes of AI, and prognosis of patients who developed AI. In total, 282 NSCLC patients were treated with anti-PD-1 antibodies, and 4 patients (1.4%) were diagnosed as AI and 6 patients (2.1%) as suspicious of AI according to the laboratory data or clinical findings. The median follow-up period was 13.6 months. All patients with AI and suspicious of AI were treated with corticosteroid replacement, and performance status (PS) was improved in 50% of patients. Two of 10 patients were thought to have central AI. Six patients of 10 patients continued to receive anti-PD-1 antibodies with corticosteroid hormone replacement after diagnosis. The median progression-free survival and overall survival were 10.2 and 15.4 months, respectively. In conclusion, the incidence of AI among NSCLC patients treated with anti-PD-1 antibodies was similar to previous studies. Corticosteroid replacement improved PS, symptoms, and laboratory data of patients with AI and suspicious of AI. Corticosteroid replacement may contribute to continuation of anti-PD-1 antibodies and survival outcome was preferable in patients with AI and suspicious of AI receiving corticosteroid treatment.

Inhibitory effect of procaterol on exercise dynamic lung hyperinflation during the 6-min walk test in stable patients with chronic obstructive pulmonary disease.

The purpose of this study was to evaluate the inhibitory effect of procaterol (procaterol hydrochloride, CAS 62929-91-3) on exercise dynamic lung hyperinflation during the 6-min walk test (6MWT) in stable chronic obstructive disease (COPD) patients. Fourteen patients with stable COPD who were referred to our clinic between July 2008 and October 2009 were evaluated in this study. After the inhalation of procaterol, values for the lung function test, including vital capacity, inspiratory capacity, forced vital capacity, and FEV1/FEV1pred showed a significant improvement. Compared to the baseline assessment, the 6-min walk distance increased by a mean of 20.5 m when measured after inhalation of procaterol (512.4 +/- 90.7 m vs. 532.9 +/- 79.8 m, p < 0.05). During the 6MWT, inspiratory capacity decreased significantly with time. The inspiratory capacity after inhalation of procaterol was improved significantly compared with placebo. The Borg scale increased significantly during the 6MWT and was attenuated after inhaling procaterol hydrochloride, though the difference between the two groups was not statistically significant. In the present study, there was a significant attenuation in exercise dynamic lung hyperinflation, suggesting the important role of the beta2-receptor agonist procaterol in the treatment of COPD. It is therefore likely that most patients with COPD may derive considerable benefit from bronchodilator therapy with procaterol.

Chronic infusion of salusin-alpha and -beta exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice.

OBJECTIVE: Human salusin-alpha and -beta are two-related peptides processed from the same precursor, preprosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-beta but suppressed by salusin-alpha. Thus we investigated the effects of salusin-alpha and -beta on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Saline (vehicle), salusin-alpha or -beta (0.6 nmol/kg/h) was continuously infused through osmotic mini-pumps into 13-week-old ApoE-/- mice for 8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester accumulation (foam cell formation), and its related gene expression in exudate peritoneal macrophages were determined. RESULTS: After 4-week infusion of salusin-beta, atherosclerotic lesions were 2.6 times greater than vehicle controls, which paralleled 1.9-fold increase in foam cell formation and up-regulation of scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol acyltransferase-1 (ACAT1). In contrast, salusin-alpha decreased serum total cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1 down-regulation. After 8-week infusion of salusin-alpha, atherosclerotic lesions were significantly suppressed by 54% compared with vehicle controls. CONCLUSIONS: Our study provided the first evidence that salusin-beta accelerates the development of atherosclerotic lesions associated with up-regulation of scavenger receptors and ACAT1 in ApoE-/- mice. Whilst, salusin-alpha exerts anti-atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1 expression.