A B S T R A C T To determine the effect of prostaglandin E1 (PGE1) infusion upon in vivo insulin secretion, serum insulin responses after an intravenous glucose pulse (2 g) were measured before and during an intravenous infusion of PGE1 (10 Ag/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE1 infusion, and insulin responses after glucose during PGE1 infusion were significantly less than control responses. Three dogs received PGE1 infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE1 before its arrival at the pancreatic artery; inhibition of insulin secretion was again seen. Inhibition of insulin secretion could not be related to the degree of arterial hypotension induced by intravenous PGE1, and despite alpha adrenergic blockade with intravenous phentolamine, PGEi-induced inhibition of glucose-stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE1 infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE1 infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity.

A new animal model was developed to determine the effect of obesity upon endogenous triglyceride secretion. Desert sand rats (Psammomys obesus), rodents which become spontaneously obese and hyperinsulinemic when given ad lib. chow, were given intravenous Triton to allow in vivo measurement of triglyceride secretion rates (TGSR). In a group of 18 fasted animals of varying body weight and degrees of obesity, TGSR correlated significantly with body weight (r = 0.68, P < 0.01) indicating that obesity was associated with accelerated endogenous release of triglyceride. In these same animals, basal plasma insulin levels correlated significantly with body weight (r = 0.78, P < 0.001) and TGSR correlated significantly with mean plasma insulin levels (r = 0.73, P <0.001), suggesting that hyperinsulinemia may have been the mechanism through which obesity enhanced TGSR. No correlation was found between basal triglyceride level and either body weight, basal insulin, or TGSR which suggested that individual triglyceride removal rates among the animals may have been variable. To test this hypothesis, seven animals were studied prospectively before and after induction of obesity. There were significant increases (P < 0.02) in all parameters, i.e., weight, plasma insulin level, TGSR, and basal triglyceride level. Thus, when each animal was used as its own control, thereby minimizing the postulated factor of variable individual triglyceride removal, increments in basal triglyceride were shown to accompany the development of obesity, hyperinsulinemia, and accelerated triglyceride secretion.These data from studies in the sand rat offer in vivo evidence that obesity leads to accelerated triglyceride