Aims/introductionThe aims of the present study were to investigate the performance of a novel sandwich enzyme‐linked immunosorbent assay (ELISA) for measuring glucagon (1–29) with monoclonal antibodies against both the C‐ and N‐terminal regions of glucagon (1–29), and to analyze the differences in plasma levels and responses of glucagon (1–29) to oral glucose loading in normal glucose tolerance (NGT) subjects and patients with type 2 diabetes mellitus.Materials and MethodsThe cross‐reactivity against proglucagon fragments using the ELISA kit and two types of conventional radioimmunoassay (RIA) kits was evaluated. A 75‐g oral glucose tolerance test was carried out with NGT subjects and patients with type 2 diabetes mellitus, and the glucagon (1–29) concentration was measured using three types of kit.ResultsThe ELISA kit clearly had the lowest cross‐reactivity against miniglucagon (19–29) and glicentin (1–61). The oral glucose tolerance test was carried out with 30 NGT and 17 patients with type 2 diabetes mellitus. The glucagon (1–29) levels measured by the ELISA kit after glucose loading were significantly higher at all time‐points in the type 2 diabetes mellitus group than in the NGT group. However, the glucagon (1–29) levels measured by one RIA kit were significantly higher in the NGT group, and those measured with the other RIA kit were approximately the same among the groups.ConclusionsThe novel sandwich ELISA accurately determines plasma glucagon (1–29) concentrations with much less cross‐reactivity against other proglucagon fragments than conventional RIA kits.
Aims/hypothesis We examined the effect of glucagon-like peptide-1 (GLP-1) on the development of diabetes and islet morphology in NOD mice by administering GLP-1 to prediabetic mice. Methods Eight-week-old female NOD mice were infused subcutaneously with human GLP-1 via a mini-osmotic pump for 4 or 8 weeks. In mice treated with GLP-1 for 4 weeks, blood glucose levels and body weight were measured. An intraperitoneal glucose tolerance test (IPGTT) and evaluation of insulitis score were also performed. Beta cell area, proliferation, apoptosis, neogenesis from ducts and subcellular localisation of forkhead box O1 (FOXO1) were examined by histomorphometrical, BrdU-labelling, TUNEL, insulin/cytokeratin and FOXO1/ insulin double-immunostaining methods, respectively.Results Mice treated with human GLP-1 for 4 weeks had lower blood glucose levels until 2 weeks after completion of treatment, showing improved IPGTT data and insulitis score. This effect continued even after cessation of the treatment. In addition to the increase of beta cell neogenesis, BrdU labelling index was elevated (0.24 vs 0.13%, p<0.001), while apoptosis was suppressed by 54.2% (p<0.001) in beta cells. Beta cell area was increased in parallel with the translocation of FOXO1 from the nucleus to the cytoplasm. The onset of diabetes was delayed in mice treated with GLP-1 for 4 weeks, while mice treated with GLP-1 for 8 weeks did not develop diabetes by age 21 weeks compared with a 60% diabetes incidence in control mice at this age. Conclusions/interpretation Continuous infusion of human GLP-1 to prediabetic NOD mice not only induces beta cell proliferation and neogenesis, but also suppresses beta cell apoptosis and delays the onset of type 1 diabetes.
Aims/Introduction: Incretins might play some pathophysiological role in glucose metabolism in diabetes and obesity; it is not clear whether or not the amount and the pattern of incretin secretion vary with different types of sugars. To evaluate the effect of two types of disaccharides on glucose metabolism and the kinetics of incretin secretion, plasma levels were measured after palatinose or sucrose ingestion in non-obese healthy participants. Materials and Methods: The study was carried out on healthy participants who were given a solution containing 50 g of palatinose or sucrose for ingestion. Blood samples were obtained before loading and after ingestion. Insulin, glucagon and incretins hormones were measured by the enzyme-linked immunosorbent assay method. Results: When the data were compared between palatinose and sucrose ingestion, both plasma glucose values at 15, 30 and 60 min, and plasma insulin values at 15 and 30 min after palatinose loading were significantly lower than those after sucrose loading. Plasma levels of total glucose-dependent insulinotropic polypeptide at 15-90 min after palatinose loading were significantly lower than those after sucrose loading. Plasma levels of total and active glucagon-like peptide-1 at 90 min and the area under the curve (60-120 min) of the total glucagon-like peptide-1 were significantly higher with palatinose-loading than with sucrose loading. Conclusion: Compared with sucrose, palatinose appears to have a more favorable effect on glucose metabolism and protection of pancreatic islets as a result of less hyperglycemic and hyperinsulinemic potency. (J Diabetes Invest,
IntroductionInsulin degludec is a new, ultra-long-acting basal insulin. The aim of this study was to analyze the changes of basal insulin dose and blood glucose profile in basal–bolus therapy of type 1 diabetes mellitus (T1DM) at the switching of basal insulin from insulin glargine or detemir to insulin degludec.MethodsSixteen patients with T1DM were enrolled. The patients underwent continuous glucose monitoring before and after the switching of insulin glargine or detemir to degludec. Ten patients treated with insulin glargine or detemir twice daily, were switched to insulin degludec with 80–90% of the prior insulin dose. The remaining six patients treated with insulin glargine once daily, were switched to insulin degludec without down titration. The changes of daily insulin dose and glycated hemoglobin (HbA1c) were also examined for 12 weeks after switching to insulin degludec.ResultsIn the patients switched from twice-daily basal insulin, no significant difference was found between before and after switching in the blood glucose profile. In the once-daily group, blood glucose levels showed a tendency to decrease after switching to the degludec treatment. During the study period, total daily insulin dose (TDD) and total daily basal insulin dose (TBD) decreased significantly in the twice-daily group, and TDD and TBD showed a tendency to decrease after switching to degludec in the once-daily group. In both groups, the changes of HbA1c were not significantly different.ConclusionIt is possible to achieve similar glycemic control with once-daily injection and lower doses of insulin degludec in patients with T1DM who have been treated with insulin glargine or detemir.
Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects. Core tip: Asymmetric dimethylarginine (ADMA) is an emerging independent biomarker for prospective cardiovascular (CV) complications. In our study, the results show that the cases with a high level of ADMA could have diabetes mellitus CV (DMCV) complications in the future within five years. Furthermore, not only ADMA but also urinary albumin was associated with DMCV complications in the multiple regression analyses. The clinical acceptation of this parameter will rely on the availability of therapies to immediately reduce ADMA such as incretin-based drugs, which could support the part of ADMA as an etiologic risk factor.
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