In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal amide structure in extracts of brain and intestine was carried out and a number of novel neuropeptides and hormonal peptides, designated neuropeptide Y, PHI, peptide YY, galanin and neuropeptide K were isolated. We recently performed a similar search in porcine pancreas and found a high concentration of a peptide having a glycine amide at its C-terminus. Here we report the isolation, primary structure and biological activity of this novel peptide. The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin. It may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.

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A study was carried out to determine the time course and degree of postoperative insulin resistance in patients undergoing elective abdominal surgery. Mean(s.e.m.) insulin sensitivity was determined before and on the first (n= lo), fifth, ninth and 20th (n= 5) days after elective open cholecystectomy using the nonnoglycaemic (4.7(0 1) mmol/l), hyperinsulinaemic (402(12) pmol/l) glucose clamp technique. Preoperative insulin sensitivity expressed as the M value varied from 2.3 to 8-2mg per kg per min. The relative reduction in insulin sensitivity was most pronounced on the first day after surgery, at a mean(s.e.m.) of 54(2) per cent. Thereafter, a large variation between individuals was Body metabolism following accidental trauma or surgery can be characterized by a state of catabolism. It has been considered that this metabolic change is regulated by altered hormonal release associated with trauma'. Thus, within minutes of the onset of trauma, plasma concentrations of noradrenaline and adrenaline are increased well above levels necessary to produce metabolic changes but return to basal values within hours after injury2-'. This increase in levels of catecholamines has been reported as related to the degree of trauma'. Trauma is also accompanied by pronounced release of growth hormone6, cortisol' and gl~cagon'.~. Levels of the last two have been reported as remaining high for 2-5 days following injury'.Early after trauma, insulin levels in humans are reported as being depressed'; it has been suggested that this effect results from inhibition by catecholamines'. However, within 24 h, a rise in insulin level is usually presentg. Despite normal or raised concentrations of insulin, glucose clearance is reduced and hyperglycaemia develops rapidly during stresslo. In addition, rates of gluconeogenesis and glycogenolysis are increased4*'. The respiratory quotient is decreased, indicating that oxidation of fat predominates over that of glucose'.' ', despite the presence of hyperglycaemia". Moreover, there is an increase in net skeletal muscle protein breakdown, resulting in a negative nitrogen b a l a n~e '~. '~. After trauma, the increase in urinary nitrogen losses has been found to coincide with increased levels of plasma insuling. Thus, several important alterations in body metabolism relate closely to a reduced effectiveness of insulin action, that is the development of insulin resistance.Early reports during the 1970s demonstrated a state of impaired glucose tolerance after surgery" as well as altered insulin responsiveness during glucose infusion tests' '*' ' , indicating alterations in carbohydrate metabolism after elective operation. However, with the introduction of the glucose clamp technique, specific determination of insulin sensitivity became possible. The development of insulin resistance in burnsz0 and sepsis's has been revealed using this method. However, less is known about insulin resistance after surgery. found during the course of recovery, and insulin sensitivity returned to normal 20 days after operati...

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