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 amylin 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 profiles were similar (n = 8), the increase in plasma lactate in the presence of AC187 was only 50.3% as high as the increase when AC187 was absent (P < 0.001). These experimental results fit with the view that some of the lactate appearing in plasma after a glucose load comes from insulin-sensitive tissues. The experiments also support the view that an important fraction of the increase in lactate depends on processes inhibited by a selective amylin antagonist, most likely amylin action in muscle.
Young
A A
AA
Amylin Pharmaceuticals Inc, San Diego, CA 92121.
Gedulin
B
B
Gaeta
L S
LS
Prickett
K S
KS
Beaumont
K
K
Larson
E
E
Rink
T J
TJ
D000595:Amino Acid Sequence; D000682:Amyloid / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D010446:Peptide Fragments; D010455:Peptides; C087166:AC 187; D019344:Lactic Acid; D005947:Glucose