We have measured peripheral plasma immunoreactive somatostatin (SRIF-LI) in 10 healthy subjects and 10 noninsulin-dependent maturity-onset diabetics (NIDDM). The mean (+/-SE) basal level of SRIF-LI in NIDDMs of 185 +/- 27 was similar to that of 174 +/- 23.5 pg/ml in age-, weight-, and sex-matched healthy subjects. Insulin hypoglycemia of equivalent magnitude induced a 113 +/- 15.8 pg/ml increase in SRIF-LI 40 min after injection in healthy subjects and no significant change in the NIDDMs. Ingestion of a mixed meal induced a biphasic rise with a mean peak of 75 +/- 30 pg/ml above basal at 15 min and a later peak of 130 +/- 35 pg/ml above basal at 120 min in healthy subjects. In NIDDM, there was no significant rise above basal, and the differences were significant at 15 and 120 min. Our findings are compatible with deficient SRIF release in these NIDDM in whom the deficient SRIF secretion may contribute to the hyperglycemia.

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We conclude that the role of uracil misincorporation and subsequent DNA damage in cytotoxicity induced by TS inhibitors, in HT29 cells, is time dependent, and that cytotoxicity caused by long-term exposure to these drugs is largely independent of resultant DNA damage, in this cell line. The inability of dutE to protect HuTu80 cells from FdUrd further suggests that the significance of uracil misincorporation resulting from TS inhibition varies among cell lines.

Epithelial cells were isolated by a vibration technique, and the mucosal scrapings of the vibrated gut and muscle layers were prepared from gastric antrum and proximal and distal small intestine and colon of the rat. The tissues were extracted with acid-ethanol, and the somatostatin-like immunoreactivity (SRIF-LI) content was determined by RIA. When expressed as a percentage of the total, the SRIF-LI content of the mucosal epithelial cells isolated by vibration was: antrum, 41%; proximal small intestine, 45%; distal small intestine, 87%; and colon, below the assay detection limit. The mucosal scrapings and muscle layers of these tissues, both areas of dense autonomic innervation, contained the remainder of the SRIF-LI.Chromatography of extracted SRIF-LI from these tissues on Sephadex G-25 superfine, equilibrated and eluted with 0.01 M formic acid, revealed that in the antrum, the SRIF-LI from all layers coeluted with synthetic cyclic tetradecapeptide SRIF . In the intestine, mucosal cells and scrapings contained principally a large molecular weight form, with an elution volume 70-75% of that between cyanocobalamin and blue dextran. In the muscle layer, two thirds of the SRIF-LI coeluted with SRIF-14, and one third eluted as the large molecular weight form. In the colon, epithelial cells contained principally the large molecular weight form of SRIF-LI; the mucosal scrapings showed an equal distribution between large and SRIF-14 forms, while in the muscle layer, the principal form coeluted with the SRIF-14 standard. These findings suggest that the major molecular form of SRIF-LI in the muscle layers at all levels in the gut is a small polypeptide with an elution volume similar to that of SRIF-14. In the mucosal layer of the antrum, this was also true, whereas in the intestine and colon, a large molecular weight species was found. This may be consistent with different molecular forms of SRIF subserving separate functions in the layers of the gut at various sites. (Endocrinology 109: 1921,1981) S OMATOSTATIN (SRIF) is a tetradecapeptide originally isolated from ovine hypothalami (1) and since shown to have a wide distribution throughout the gut (2-4), central and peripheral nervous systems (5, 6), also being found in pancreatic D cells (2, 7). In the gastrointestinal tract, SRIF has been observed by immunocytochemical techniques to be present in the endocrine cells of the gut epithelium (7, 8) and in neural elements (6). In this study, the SRIF-like immunoreactivity (SRIF-LI) in the epithelial, submucosal, and muscular layers of the gastric antrum, small intestine, and colon of the rat was quantified, and its molecular heterogeneity was explored.