Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production.
The adipose-derived hormone resistin is postulated to link obesity to insulin resistance and diabetes. Here, the infusion of either resistin or the resistin-like molecule-beta (RELMbeta) rapidly induced severe hepatic but not peripheral insulin resistance. In the presence of physiologic hyperinsulinemia, the infusion of purified recombinant resistin, increasing circulating resistin levels by approximately twofold to 15-fold, inhibited glucose metabolism such that lower rates of glucose infusion were required to maintain the plasma glucose concentration at basal levels. The effects of resistin and RELMbeta on in vivo insulin action were completely accounted for by a marked increase in the rate of glucose production. These results support the notion that a novel family of fat- and gut-derived circulating proteins modulates hepatic insulin action.
Rajala
Michael W
MW
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Obici
Silvana
S
Scherer
Philipp E
PE
Rossetti
Luciano
L
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D052243:Resistin
D006729:Hormones, Ectopic; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011994:Recombinant Proteins; D052243:Resistin; C499622:Retn protein, rat; C486575:Retnla protein, rat; C486522:Retnlb protein, mouse; D020932:Nerve Growth Factor; D005947:Glucose