Characterisation of somatostatin release from the pancreas

Summary The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 mol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.     

The circulating IGF system and its relationship with 24-h glucose regulation and insulin sensitivity in healthy subjects

OBJECTIVE AND DESIGN: It has been suggested that circulating free IGF-I participates in glucose homeostasis and that IGFBP-1 reflects changes in insulin sensitivity. To study this further, we examined 10 healthy, nonobese subjects under standardized conditions for 24 h with and without an intravenous infusion of glucose, the latter in order to augment insulin sensitivity. Serum was collected every 2 h for analysis of free and total IGFs, IGFBP-1, - 2 and - 3 and the acid labile subunit (ALS). Insulin sensitivity was estimated at the end of each 24-h study period by use of the hyperinsulinaemic euglycaemic clamp technique. RESULTS: Glucose infusion resulted in mild hyperglycaemia (P < 0.0001), a reduction in IGFBP-1 by approximately 40% (P < 0.0003), and increased insulin and C-peptide levels (P < 0.0001). Glucose infusion also increased insulin sensitivity (P < 0.003). However, despite the reduction in IGFBP-1, glucose infusion did not increase free IGF-I over the control level, and free IGF-II was slightly reduced (P < 0.02). Irrespective of glucose infusion, free IGF-I and -II remained stable during daytime (i.e. they were unresponsive to meal-related changes in plasma glucose), but both free fractions decreased during the night, reaching nadir at 04.00 h. None of the other members of the IGF system showed any relationship with plasma glucose levels. Finally, we failed to observe any relationship between changes in insulin sensitivity and the circulating IGF system. CONCLUSION: We found no evidence that the circulating IGF system is involved in meal-related blood glucose regulation or that it reflects short-term changes in insulin sensitivity in healthy, nonobese subjects. However, we cannot preclude that the observed changes in circulating IGFBP-1 may affect the glucose-lowering effect of IGF-I and -II at the local tissue level.     

Pancreatic and intestinal processing of proglucagon in man

Summary We developed antisera and radioimmunoassays against synthetic replicas of glucagon-like peptide-1 (1–36) and -2, predicted products of the glucagon precursor, and against glucagon-like peptide-1 (7–36) identical to the sequence of glucagon-like peptide-1, but lacking its first six N-terminal amino acids. With these tools, we studied the localisation and molecular nature of glucagon-like immunoreactivity in human pancreas, small intestine and plasma. By immunohistochemistry glucagon-like peptide-1, and glucagon-like peptide-2 immunoreactivity coexisted with glucagon in pancreatic islet cells and with enteroglucagon in small intestinal enteroglucagon-producing cells. By chromatography of tissue extracts we found that glucagon-like peptide-1 and glucagon-like peptide-2-immunoreactivities in the human pancreas (307±51 and 107±37 pmol/g tissue) were mainly contained in a large peptide, whereas in the small intestine glucagon-like peptide-1 and glucagon-like peptide-2 immunoreactivities were found in separate smaller molecules (49±21 and 77±28/g tissue). By isocratic high pressure liquid chromatography of the large pancreatic glucagon-like peptide we found that this peptide is heterogeneous. By chromatographic analysis glucagon-like peptide-1 immunoreactivity in fasting plasma was mainly found in a large peptide corresponding to the pancreatic form, while after a meal a smaller molecular form coeluting by gel filtration with glucagon-like peptide-1 predominated.     

Glucagon-like peptide-1, a new hormone of the entero-insular axis

Summary The post-translational processing of proglucagon in the small intestine gives rise to glucagon-like peptide-1 (PG 78–107 amide) which has profound effects on the endocrine pancreas, and in many species also on the stomach. Glucagon-like peptide-1 (PG 78–107 amide) is secreted in man in response to physiological stimuli e.g. a mixed meal. Glucagon-like peptide-1, in concentrations corresponding to those observed in response to meals, strongly stimulates insulin secretion, in all mammals studied, even more potently than the gastric inhibitory peptide. Thus, glucagon-like peptide-1 fulfills the classic criteria for being a hormone and is likely to be a new incretin. The glucagon inhibitory effect of glucagon-like peptide-1 (PG 78–107 amide) probably further potentiates the effect of glucagon-like peptide-1 on glucose metabolism and distinguished this peptide from other intestinal peptides which have been proposed as incretins. Glucagon-like peptide-1 also inhibits gastric acid secretion and gastric emptying in man. The latter delays nutrient entry to the intestine and thereby diminishes meal-induced glucose excursions. Elevated plasma concentrations of immunoreactive glucagon-like peptide-1 have been reported in Type 2 (noninsulin-dependent) diabetic patients, however, the consequences of the elevation are not yet known. However, elevated levels of glucagon-like peptide-1 in patients with increased gastric emptying rate (post-gastrectomy syndromes) may be responsible for the exaggerated insulin secretion seen in these patients.     

Aerobactin production of serotyped Escherichia coli from urinary tract infections

Aerobactin production was examined by a bioassay in 467 Escherichia coli urinary strains from girls. All strains were of known OKH serotype. 139, 119 and 112 strains were isolates from pyelonephritis (Py), cystitis (Cy) and asymptomatic bacteriuria (ABU), respectively, and 97 were from fecal samples of healthy girls (FN). The incidence of aerobactin production was significantly higher among Py strains than among ABU and FN strains (P<0.001) and also significantly higher than among Cy strains (P<0.01). Aerobactin production was associated with serotype, e.g. the majority of 06K2H1 strains and of 016K1H6 were positive while e.g. the 06K13H1 strains were negative. There was no consistent pattern of coappearance of aerobactin and hemolysin.