Previous exposure to glucose enhances somatostatin secretion from the isolated perfused rat pancreas

Abstract

Previous exposure to glucose enhances insulin and depresses glucagon secretion by the pancreas. We have investigated whether secretion of somatostatin is also influenced by a glucose priming effect. In perfused rat pancreas from 36 h fasted rats a 5 min pulse of arginine (8 mmol/l) rapidly elicited a peak of somatostatin release. A similar somatostatin response was evoked by a second, identical, pulse of arginine after perfusion with "basal" glucose (3.9 mmol/l) for 45 min. On the other hand when 27.7 mmol/l D-glucose, was administered for 20 min between arginine pulses, there was significant stimulation of somatostatin secretion. When arginine was re-introduced 15 min after the cessation of the pulse of elevated glucose the magnitude of the arginine-induced peak (min 0-2 of stimulation) was increased from 16.2 +/- 4.1 to 33.1 +/- 4.7 pg/2 min, p less than 0.01, relative to the first stimulation with arginine. None of these effects of glucose could be reproduced by D-galactose. The somatostatin response to arginine was higher in pancreata from fed than from 36 h fasted animals as was also basal release (22.8 +/- 5.0 vs 9.0 +/- 2.0 pg/min). In the fed state the response to the second pulse of arginine was however reduced by 50% after perfusion with "basal" glucose. This decrease in responsiveness was counteracted by perfusion with 27.7 mmol/l glucose for 20 min between the arginine pulses. It is concluded that previous exposure to an elevated concentration of glucose enhanced D-cell responsiveness to arginine in the fasted as well as the fed state.

Diabetes reduces β-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction

“…The insulin accumulated in the incubation medium was measured as described. 23 Islet insulin content was measured after acid-ethanol extraction 24 of islets retrieved from batch incubations. Western blot.…”

B cell insensitivity in a rat model of non-insulin-dependent diabetes. Evidence for a rapidly reversible effect of previous hyperglycemia.

“…At the end of experiments, perfused pancreases were rapidly frozen. They were then kept at -70°C until extraction of insulin was performed in perfused pancreas, as previously described (14).…”

Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion

“…After the incubation, an aliquot of the medium was stored at À70 C for measurement of insulin, and the islets were washed with glucose-free KRB buffer and insulin from the islets was extracted with acid ± alcohol. 15 Insulin was measured by radioimmunoassay with the addition of charcoal to separate free and bound antibody. 16 Glucose utilization and oxidation For the measurement of glucose utilization and oxidation, groups of 25 islets were placed in incubation vials with either 5.5 or 16.7 mM glucose (in duplicate), 0.5% BSA (fraction V) and 1 mCi of H]glucose and 1 mCi of [U-14 C]glucose in 100 ml of KRB.…”