著者

Chiho Oba-Yamamoto Hiraku Kameda Hideaki Miyoshi Tomonori Sekizaki Takahiro Takase Tsuyoshi Yanagimachi Yukihiro Fujita Hiroshi Nomoto Kyu Yong Cho Akinobu Nakamura So Nagai Tatsuya Atsumi

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.60, no.15, pp.2375-2383, 2021-08-01 (Released:2021-08-01)

参考文献数

23

被引用文献数

1

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Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP, are frequently administered to diabetic patients, including those with acromegaly. We aimed to determine whether or not the administration of a DPP4i increases GH concentration, especially in patients demonstrating PI-GH during a DPP4i-OGTT, in which a DPP4i was administered immediately before 75-g OGTT. Methods This prospective cross-sectional study was carried out on acromegalic patients admitted to Hokkaido University hospital between June 2011 and May 2018. The participants underwent both 75-g OGTT and DPP4i-OGTT. For those who underwent surgery, immunohistochemical staining and quantitative polymerase chain reaction (PCR) for the GIP receptor (GIPR) were performed on the resected pituitary adenomas. Results Twenty-five percent of the participants had PI-GH confirmed (3 of 12 cases). Two of the three participants who demonstrated PI-GH exhibited higher circulating GH concentrations during DPP4i-OGTT than during OGTT. The increase in plasma glucose was reduced during DPP4i-OGTT compared to during 75-g OGTT, suggesting that the increase in GH during DPP4i-OGTT was due not to high glucose concentrations but instead increased GIP caused by the administration of DPP4i. The adenoma from one participant with PI-GH displayed positive immunostaining for GIPR and a higher GIPR messenger ribonucleic acid (mRNA) expression than the others. Conclusion DPP4i may enhance the GH secretion response during glucose loading, especially in individuals with PI-GH.

著者

Hiroyuki TSUDA Yutaka OHSHIMA Hiroshi NOMOTO Ken-ichi FUJITA Eiji MATSUDA Masaaki IIGO Nobuo TAKASUKA Malcolm A. MOORE

出版者

日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

vol.19, no.4, pp.245-263, 2004 (Released:2004-09-29)

参考文献数

152

被引用文献数

132 154

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Increasing attention is being paid to the possibility of applying cancer chemopreventive agents for individuals at high risk of neoplastic development. For this purpose by natural compounds have practical advantages with regard to availability, suitability for oral application, regulatory approval and mechanisms of action. Candidate substances such as phytochemicals present in foods and their derivatives have been identified by a combination of epidemiological and experimental studies. Plant constituents include vitamin derivatives, phenolic and flavonoid agents, organic sulfur compounds, isothiocyanates, curcumins, fatty acids and d-limonene. Examples of compounds from animals are unsaturated fatty acids and lactoferrin. Recent studies have indicated that mechanisms underlying chemopreventive potential may be combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects, with modification of drug-metabolizing enzymes, influence on the cell cycle and cell differentiation, induction of apoptosis and suppression of proliferation and angiogenesis playing roles in the initiation and secondary modification stages of neoplastic development. Accordingly, natural agents are advantageous for application to humans because of their combined mild mechanism. Here we review naturally occurring compounds useful for cancer chemprevention based on in vivo studies with reference to their structures, sources and mechanisms of action.