SELECTIVE AMYLIN ANTAGONIST SUPPRESSES RISE IN PLASMA LACTATE AFTER INTRAVENOUS GLUCOSE IN THE RAT - EVIDENCE FOR A METABOLIC ROLE OF ENDOGENOUS AMYLIN

Data presented here provide the first demonstration that circulating a mylin regulates metabolism in vivo, and support an endocrine hormonal role that is distinct from its autocrine action at pancreatic islets. When rats were pre-treated with the potent amylin antagonist AC187 (n = 18), and then administered a 2 mmol glucose load, the rise in plasma lactate was less than in rats administered glucose only (n = 27; P < 0.02). When rats were treated so that plasma glucose and insulin profi les were similar (n = 8), the increase in plasma lactate in the presen ce of AC187 was only 50.3% as high as the increase when AC187 was abse nt (P < 0.001). These experimental results fit with the View that some of the lactate appearing in plasma after a glucose load comes from in sulin-sensitive tissues. The experiments also support the view that an important fraction of the increase in lactate depends on processes in hibited by a selective amylin antagonist, most likely amylin action in muscle.