Treatment of Streptozotocin-Diabetic Dogs With a Long-Acting Somatostatin Analog

Abstract

A long-acting somatostatin analog, Wy-41,747, improved glucose homeostasis in steptozotocin-diabetic dogs. In insulin-withdrawn, fasted dogs, a single 100 μg/kg s.c. injection of Wy-41,747 significantly suppressed plasma glucagon levels for 2 h (a nadir of 53 ± 8% of basal being reached at 1 h) and plasma glucose for 3 h (77 ± 5% of basal); even more potent suppression of glucagon and glucose levels was observed during experiments with 500 μ/kg of Wy-41,747. During meal studies, the combined administration of Wy-41,747 (100 μ/kg) and insulin resulted in lower postprandial glucagon and glucose levels than did the administration of insulin alone. When the somatostatin analog was given alone to fed animals, a rise in glucose occurred 4-5 h after the meal, suggesting the possibility of delayed absorption under these conditions. Improved glucose tolerance profiles followed oral administration of glucose or 14C-3-O-methyl glucose; a normal or near-normal time course of absorption was observed with diminished peak plasma glucose or 14C levels. No major malabsorption of carbohydrate occurred in the 14C-3-O-methyl glucose study, since only low levels of 14C were found in the feces of peptide-treated dogs. No undesirable gastrointestinal effects were noted during these studies. In conclusion, administration of a singlesubcutaneous dose of the long-acting somatostatin analog Wy-41,747 to streptozotocin-diabetic dogs lowered fasting plasma glucose levels and augmented insulin action in lowering postprandial glucose levels.