2 morpholinoethanesulfonic acid

All reagents and samples were used without further purification. Methanol (MeOH) and hydrochloric acid (HCl) were obtained from Kanto Chemical Co., Inc. 2-Morpholinoethanesulfonic acid (MES) was purchased from Dojindo Laboratories Co., Ltd. Reagents purchased from Sigma-Aldrich Co. LLC. were zinc (Zn²⁺) perchlorate, copper (Cu²⁺) perchlorate, nickel (Ni²⁺) perchlorate, cobalt (Co²⁺) perchlorate, lead (Pb²⁺) perchlorate, and mercury (Hg²⁺) perchlorate. Sodium hydroxide (NaOH), a commercially available river sample with trace elements in river water (Elevated Level, NMIJ CRM 7202-c), and Daigo's artificial seawater SP for marine microalgae medium were obtained from FUJIFILM Wako Pure Chemical Industries, Ltd. The synthetic methodology for 1_poly was established in our previous report.^{41 (link)}

Plasma (40 microliters [μL]) was extracted with the addition of 400 μL of ice-cold methanol containing the internal standards (10 millimolars [mM] l-methionine sulfone [Wako], 100 mM 2-morpholinoethanesulfonic acid [Dojindo], 100 mM D-10-camphorsulfonic acid [Wako]), 400 μL of chloroform, and 120 μL of water. After centrifugation at 10,000 × g for 3 min at 4 °C, the separated aqueous layer was filtered through a 5 kilodalton (kDa) cutoff filter (Millipore) to remove protein contamination. The filtrate (300 μL) was lyophilized and dissolved in 20 μL water containing the 2 types of reference compounds (200 μM each of trimesate [Wako] and 3-aminopyrrolidine [Sigma-Aldrich]) for migration time and then injected into the capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) system (Agilent Technologies)^{36 (link)–38 (link)}. Among the measured molecules, GIP (active) was measured using an ELISA kit. Blood hormones and some metabolites were measured according to methods developed by LSI Medience Co., Ltd. The methods used to measure each of these molecules are listed in Supplementary Data 5; among these, the amino acid fractions measured by liquid chromatography–mass spectrometry (LC–MS) are listed in Supplementary Data 6, and the metabolites measured by CE-TOFMS are listed in Supplementary Data 7.

Internal standards for LC‐MS/MS analysis, 2‐morpholinoethanesulfonic acid and 12S‐hydroxy‐5Z,8Z,10E,14Z‐eicosatetraenoic‐5,6,8,9,11,12,14,15‐d8 acid (12S‐HETE‐d8), were obtained from Dojindo (Kumamoto, Japan) and Cayman Chemical (Ann Arbor, MI, USA), respectively. The MxP® Quant 500 kit was obtained from Biocrates Life Sciences AG (Innsbruck, Austria). All solvents used for MS were of high‐performance liquid chromatography grade.