Interaction between altered insulin and lipid metabolism in CEACAM1-inactive transgenic mice.
Inactivation of CEACAM1 in L-SACC1 mice by a dominant-negative transgene in liver impairs insulin clearance and increases serum free fatty acid (FFA) levels, resulting in insulin resistance. The contribution of elevated FFAs in the pathogenesis of insulin resistance is herein investigated. Treatment of L-SACC1 female mice with carnitine restored plasma FFA content. Concomitantly, it normalized insulin levels without directly regulating receptor-mediated insulin internalization and prevented glucose tolerance in these mice. Similarly, treatment with nicotinic acid, a lipolysis inhibitor, restored insulin-stimulated receptor uptake in L-SACC1 mice. Taken together, these data suggest that chronic elevation in plasma FFAs levels contributes to the regulation of insulin metabolism and action in L-SACC1 mice.
Dai
Tong
T
Departments of Pharmacology and Therapeutics, Medical College of Ohio, Toledo, Ohio 43614, USA.
Abou-Rjaily
George A
GA
Al-Share'
Qusai Y
QY
Yang
Yan
Y
Fernström
Mats A
MA
Deangelis
Anthony M
AM
Lee
Abraham D
AD
Sweetman
Lawrence
L
Amato
Antonino
A
Pasquali
Marzia
M
Lopaschuk
Gary D
GD
Erickson
Sandra K
SK
Najjar
Sonia M
SM
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D001710:Biotin / Q000737:chemistry; D002272:Carcinoembryonic Antigen; D002331:Carnitine / Q000737:chemistry; D015815:Cell Adhesion Molecules; D002462:Cell Membrane / Q000378:metabolism; D003065:Coenzyme A / Q000737:chemistry; D004952:Esters; D005227:Fatty Acids / Q000737:chemistry; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D005260:Female; D005799:Genes, Dominant; D005947:Glucose / Q000737:chemistry; D019298:Glucose-6-Phosphate / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009525:Niacin / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D019076:Transgenes; D014867:Water / Q000737:chemistry
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D004952:Esters; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; D014867:Water; D009525:Niacin; D019298:Glucose-6-Phosphate; D001710:Biotin; D005947:Glucose; D002331:Carnitine; D003065:Coenzyme A; D020155:3-Hydroxybutyric Acid