The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D\ x=r eq-\ glucose, D-galactose, D-glucuronic acid, 3-0-methyl-D\x=req-\ glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D-fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon-like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D\ x=r eq-\ glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity.Gut glucagon-related peptides are distributed in enteroendocrine L cells throughout the gastroin¬ testinal tract, with highest concentrations localized in the distal small intestine and the colon (1-3). The precursor molecule proglucagon contains, in addi¬ tion to the amino acid sequence of the hormone glucagon and glicentin-related polypeptide (proglucagon(l-30)), a sequence of further 96 amino acids. The latter fragment contained two glucagon-like peptides, glucagon-like peptide (GLP)-l (proglucagon(72-108)) and glucagon-like peptide-2 (proglucagon(126-159)), which were flanked by basic dipeptides, potential post-translational cleavage sites (4,5) Proglucagon is shown to be processed into glicentin (proglucagon 1-69) (6) and the two glucagon-like peptides in the ileum. Recently, the complete amino acid sequences of human and porcine gut GLP-1 have been shown to correspond to that of proglucagon(78-107) amide (7) which was the product of further cleavage and amidation of proglucagon(72-108). A synthetic peptide corresponding to proglucagon(78-107) amide has been reported to have several interesting effects: at physiological concentrations it strongly stimulates insulin secretion (8,9) suppresses gluca¬ gon secretion (10,11), and inhibits acid secretion (12). GLP-1 immunoreactivity has been shown to be released into the circulation after a mixed meal and in response to a glucose load (13). Thus, GLP-1 has been suggested to play an important role in carbohydrate metabolism as an "incretin". How¬ ever, the mechanism of its secretion from the in¬ testinal tract is not known.To clarify this point...

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SUMMARY1. In order to study the kinetics of the oxygen egress from human red cells in the 50 sec-20 min time range, an apparatus for measuring the oxygen dissociation process was constructed, combining a spectrophotometer with an oxygen electrode of quick response. 3. The r value was always 1x0 for the haemolysate, but it was less than 1-0 for the normal red cells. Further, the oxygen dissociation curve of red cells obtained at higher Vmax was distorted, due to the non-equilibration between intra-and extracellular oxygen concentrations.4. The r value was (i) independent of the amounts of the allosteric effectors (2,3-diphosphoglycerate and H+) but (ii) dependent on the haemoglobin contents and (iii) dependent on the amounts of the membrane cholesterol. Therefore, the r value reflected only the process of the oxygen diffusion but not the 'chemical reaction' rate. The 'barrier' of the oxygen diffusion decreased at lower haemoglobin contents, but increased at higher cholesterol contents in the membrane.