Effect of Low-Dose Somatostatin Infusion on Pancreatic and Gastric Endocrine Function in Lean and Obese Nondiabetic Human Subjects

The present study was designed to compare, in lean and obese nondiabetic subjects, basal and postprandial levels of peripheral venous plasma insulin, glucagon, gastrin, pancreatic polypeptide (PP), glucose, triglycerides, and somatostatin-like immunoreactivity (SLI) during the infusion of synthetic somatostatin-14 or saline. Thirty-five minutes before the ingestion of the test meal, an infusion of synthetic somatostatin-14 was started at a rate of 0.5 ng/kg · min and was increased to 1.0 ng/kg min 30 min after consumption of the meal and lasted foranother 90 min. During the infusion of saline, basal peripheral vein levels of insulin, gastrin,and triglycerides were elevated in obese subjects, whereas basal plasma SLI levels were significantly lower compared with the lean controls. Basal glucagon and PP levels were similar in both groups. After the ingestion of the meal, augmented concentrations of insulin and gastrin were observed in the obese subjects, whereas postprandial SLI and PP levels were reduced. Chromatography of fasting plasma revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-10 column. The rise in SLI after the meal was due to an increase of SLI coeluting with somatostatin-28 and somatostatin-14. During the infusion of somatostatin, only basal insulin levels were significantly lower in the obese subjects, whereas no change of any basal hormone level was observed in the lean group. During the infusion of somatostatin, SLI levels were elevated by 20–30 pg/ml in both groups compared with the saline controls. During the infusion rate of 0.5 ng/ kg · min, only postprandial PP levels were reduced significantly in the obese group, while all the other parameters were unaffected in both groups. At 1.0 ng/ kg · min, postprandial plasma insulin, PP, and gastrin levels were reduced significantly in the obese group,anda transient decrease of glucagon was observed in both groups in comparison with the respective saline control experiments. These data demonstrate an augmented inhibitory effect of intravenously infused synthetic somatostatin on basal and postprandial insulin and postprandial gastrin and PP release in obese subjects. This increased responsiveness to somatostatin suggests that reduced postprandial immunoreactive SLI levels in the obese group might represent true biologically relevant hyposomatostatinemia, facilitating the hypersecretion of some but certainly not all gastric and pancreatic endocrine factors in obesity.