GLUCOSE-TOLERANCE AND POSTPRANDIAL GLUCOSE AND INSULIN KINETICS IN RATS WITH SHORT-TERM AND LONG-TERM ALPHA(1)-ADRENERGIC BLOCKADE

The present study was designed to evaluate the acute and chronic effec ts of the alpha(1)-adrenergic antagonist prazosin (Praz) on glucose to lerance and on postprandial plasma glucose and insulin kinetics. Rats were fed a high sucrose diet for 3 weeks, to which Praz (3 mg/kg/day) was added or not. They were then accustomed to ingest a meal 1 h after a single intraperitoneal (i.p.) injection of saline or Praz (1 mg/kg) . Plasma levels of glucose and insulin were recorded at various times after meal intake. In addition, a fasting intravenous glucose toleranc e test (IVGTT) was performed. In the chronic control cohort, pre-IVGTT plasma glucose and insulin levels were slightly but significantly hig her after acute Praz than after acute saline administration. Factorial analysis of variance (ANOVA) showed that the increase in plasma gluco se and insulin after intravenous (i.v.) glucose administration was als o slightly greater in the animals that received acute Praz than in the ir saline counterparts. In contrast, after chronic treatment with Praz , pre- and post-IVGTT plasma glucose and insulin concentrations were i dentical in groups acutely injected with saline or Praz. In the chroni c control cohort, preprandial plasma glucose and insulin measured in a sample collected before acute injection of saline or Praz were simila r in both groups. The postprandial increase in plasma glucose and insu lin was potentiated by the acute administration of Praz. Fasting plasm a glucose and insulin concentrations were also similar in both groups chronically treated with Praz, and acute administration of the blocker still potentiated the increase in plasma glucose and insulin that fol lowed meal intake. Chronic treatment alone did not affect postprandial glucose and insulin concentrations, and acute injection of Praz had c omparable effects whether rats were chronically treated with the block er or not. Therefore, potentiation of the glucose and insulin response to meal intake by Praz persisted after chronic treatment but required the acute presence of the blocker. However, repeated exposure to acut e bouts of postprandial hyperinsulinemia induced by Praz did not lead to deterioration of insulin sensitivity or of the capacity of the panc reas to secrete insulin, as suggested by a normal response of glucose and insulin to IVGTT.