著者

Ayako Hoshiyama Kazumi Fujimoto Ryo Konno Sayaka Sasaki Akari Momozono Yoshio Kodera Masayoshi Shichiri

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ18-0472, (Released:2019-04-26)

被引用文献数

3

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Glucose-dependent insulinotropic polypeptide (GIP), secreted from enteroendocrine K cells, has potent insulin-releasing and extrapancreatic glucoregulatory activities. However, exogenous GIP has less potent biological effects compared with another incretin hormone, GLP-1, which limits its use for the treatment of type 2 diabetes. The fate and secretion of administered native GIP remain unclear. The aim of this study was to identify plasma binding proteins for human GIP. Fluorescent-labelled GIP was added to fresh human plasma and subjected to clear native polyacrylamide gel electrophoresis (CN-PAGE). Then fluorescent protein bands were in-gel trypsin-digested and subjected to liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis, revealing the presence of albumin, immunoglobulin G (IgG) and transferrin. In contrast to GIP, the binding of fluorescent GLP-1 and glucagon to plasma protein fractions were minimal. CN-PAGE analysis of synthetic GIP incubated with human serum albumin, purified IgG or transferrin, and subsequent western blot analysis revealed that GIP binds to each of these proteins. Taken together, these results indicate that GIP readily binds to albumin, IgG and transferrin, three plasma proteins highly abundant in the human peripheral circulation. Separation of protein complexes using CN-PAGE and the identification of in-gel digested proteins by LC-MS/MS analysis provide a promising strategy to identify plasma binding proteins for bioactive peptides.

著者

Satoru Bando Raishi Ichikawa Tomomi Taguchi Kazumi Fujimoto Tetsuya Motomiya Madoka Taguchi Koji Takano Masayoshi Shichiri Takeshi Miyatsuka

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ21-0696, (Released:2022-01-22)

被引用文献数

4

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The insufficient activity of insulin and the hyperactivity of glucagon are responsible for glucose intolerance in patients with type 2 diabetes. Whereas sodium-glucose cotransporter-2 (SGLT2) inhibitors improve blood glucose levels in patients with type 2 diabetes, their effects on the secretion profiles of glucagon and incretins remain unclear. Therefore, to investigate the effects of the SGLT2 inhibitor luseogliflozin on metabolic and endocrine profiles, 19 outpatients with type 2 diabetes were administered luseogliflozin for 12 weeks. It is of note that all subjects were treated only with diet and exercise therapy, and we were able to investigate the effects of luseogliflozin separately from the effects of other antidiabetic agents. Body weight, body fat mass, fat-free mass, and muscle mass were significantly reduced after 12 weeks of luseogliflozin administration. Glycosylated hemoglobin significantly decreased from the baseline of 8.2% ± 0.8% to 7.3% ± 0.7% (p < 0.0001). The meal tolerance test demonstrated that luseogliflozin significantly recovered glucose tolerance, accompanied by improved insulin resistance and β-cell function, whereas glucagon secretion was unaffected. Furthermore, GLP-1 secretion was significantly increased after luseogliflozin administration. Thus, luseogliflozin improved metabolic and endocrine profiles accompanied by increased GLP-1 secretion in type 2 diabetic patients without any antidiabetic medication, but did not affect glucagon secretion.