[In vitro and in vivo effect of gold thioglucose on the insulin- and glucagon-secretion of the isolated perfused rat pancreas]

Abstract

Effects of gold thioglucose on the insulin and glucagon secretion by the isolated perfused pancreas of Wistar rats in vivo and in vitro Gold thioglucose (GTG), hitherto administered predominantly to mice can also be used in rats in a non toxic dosage, if GTG is injected intravenously (i.v.) together with sodium hexobarbital. Wistar rats tolerate a single injection of GTG in doses ranging from 40 to 1200 mg/kg bw. GTG (10 mmol/l in the perfusion medium) has no in vitro effect--tested by the isolated perfused rat pancreas--on the basal (5.5 mmol/l glucose) or stimulated (11 mmol/l glucose) insulin (IRI)-secretion. This is valid also for glucagon (IRG)-secretion. After in vivo injection of GTG (600 mg/kg bw, together with sodium hexobarbital (10 mg/100 g bw, i.v.] extensive alterations of IRI- and IRG-secretion result as tested under in vitro conditions in the isolated perfused pancreas of the rat, Glucose stimulation (11 mmol/l) causes a hyperinsulinism and a hypersecretion of IRG, a so-called paradoxical glucagon secretion, lasting for 2 days while IRI secretion is already diminished. At the same time food intake is very low and the body weight decreases. Ten days later the body weight has reached the starting value again and the IRI secretion shows again signs of hyperinsulinism. Six months after a single injection of GTG (600 mg/kg bw, i.v.) the rats were obese and react after glucose stimulation with hyperinsulinism and again with a paradoxical glucagon secretion. The blood glucose levels were normoglycaemic, whereas serum IRI rose in parallel with development of the obesity. Also with histological methods we could distinguish an acute from a chronic phase of GTG toxicity visible in the tested organs (liver, kidney, thyroid gland). The endocrine pancreas reacts after a single injection of GTG with a lowered number of B cells. The remaining cells reveal variable amounts of degranulation. In the early phase the hypothalamus, in particular the ventromedial hypothalamic nucleus, shows most clearly signs of destruction and 6 months after a single injection of GTG the number of cells is still reduced in this region. We conclude that GTG reacts primarily on the hypothalamus and modulates the reactivity of the endocrine pancreas in a permanent manner via the vegetative nervous system, because we test the function of the pancreas in an in vitro system. As a consequence the threshold of the B and A cell against the stimulus glucose is altered in two ways.(ABSTRACT TRUNCATED AT 400 WORDS)