Evidence that amylin stimulates lipolysis in vivo: a possible mediator of induced insulin resistance.
The present study investigated the role of amylin in lipid metabolism and its possible implications for insulin resistance. In 5- to 7-h-fasted conscious rats, infusion of rat amylin (5 nmol/h for 4 h) elevated plasma glucose, lactate, and insulin (P <0.05 vs. control, repeated-measures ANOVA) with peak values occurring within 60 min. Despite the insulin rise, plasma nonesterified fatty acids (NEFA) and glycerol were also elevated (P < 0.001 vs. control), and these elevations (80% above basal) were sustained over the 4-h infusion period. Although unaltered in plasma, triglyceride content in liver was increased by 28% (P < 0.001) with a similar tendency in muscle (18%, P = 0.1). Infusion of the rat amylin antagonist amylin-(8-37) (125 nmol/h) induced opposite basal plasma changes to amylin, i.e., lowered plasma NEFA, glycerol, glucose, and insulin levels (all P < 0.05 vs. control); additionally, amylin-(8-37) blocked amylin-induced elevations of these parameters (P < 0.01). Treatment with acipimox (10 mg/kg), an anti-lipolytic agent, before or after amylin infusion blocked amylin's effects on plasma NEFA, glycerol, and insulin but not on glucose and lactate. We conclude that amylin could exert a lipolytic-like action in vivo that is blocked by and is opposite to effects of its antagonist amylin-(8-37). Further studies are warranted to examine the physiological implications of lipid mobilization for amylin-induced insulin resistance.
Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia. ye@garvan.unsw.edu.au
J M
JM
Ye
M
M
Lim-Fraser
G J
GJ
Cooney
G J
GJ
Cooper
M A
MA
Iglesias
D G
DG
Watson
B
B
Choong
E W
EW
Kraegen
D000682:Amyloid / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D058228:Islet Amyloid Polypeptide; D019344:Lactic Acid / Q000097:blood; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
D000682:Amyloid; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D008055:Lipids; D010446:Peptide Fragments; D011719:Pyrazines; D014280:Triglycerides; C109255:amylin (8-37); D019344:Lactic Acid; C027696:acipimox