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...

An outbreak of Escherichia coli O157:H7 infection occurred in July 1996 in Sakai City. About 5000 children were infected, 122 of whom developed hemolytic uremic syndrome (HUS). In this outbreak, almost all patients were administrated some type of antibiotics. The effects of antibiotics on E. coli O157 associated hemorrhagic colitis (HC) have been controversial. In this study, we focused on the effects of antibiotics on development of HUS in the HUS in the Sakai outbreak. We retrospectively determined the antibiotics administrated within three days after the onset of HC, clinical courses, and laboratory data of 301 patients who were hospitalized and identified as Escherichia coli O157 infection by stool culture, from results of questionnaires sent by the Osaka Prefecture Medical Association to hospitals in Osaka Prefecture. The antibiotics used could be identified for 216 patients. The incidence of HUS among these patients was 11.6%. They were divided into 19 groups based on the type of antibiotics administrated. The incidence of HUS in the new quinolone (3.7%) group was low, but was high in the intravenous cephalosporin (18.2%) group. The differences in the incidence of HUS among the 19 antibiotic groups was significant (p < 0.05) on analysis of covariance which eliminated the contributions of variables including age, sex and laboratory data. These findings indicate that the suitable antibiotics can prevent the development of E. coli O157-associated HUS.

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