Effects of free fatty acids on plasma resistin and insulin resistance in awake rats.
Resistin has been postulated to play a role in obesity-related insulin resistance. To explore this possibility, we have investigated effects of acute euglycemic (5.2+/-0.1 mmol/L) hyperinsulinemia (96+/-8 microU/mL) with and without concurrent infusion of lipid plus heparin (to raise or lower plasma free fatty acid [FFA] levels) on glucose turnover and plasma resistin levels in alert rats. Plasma FFA concentrations increased during lipid/heparin (L/H) infusion (from 0.82 to 2.86 mmol/L, P<.001) and decreased (from 0.83 to 0.21 mmol/L, P<.001) in controls who were infused with insulin but not with L/H. L/H infusion reduced insulin suppression of endogenous glucose production by approximately 90% (from 28.9 to 3.1 mg. kg-1 . min-1, P<.001) and insulin-stimulated glucose uptake (glucose rate of disappearance) by 78% (from 30.8% to 6.9%, P<.001). Plasma resistin levels increased by 46% (from 39.9 to 58.4 microg/L, P<.05) during L/H infusion and did not change in controls (39.7 vs 39.3 microg/L). Plasma ghrelin levels decreased by 41% (from 892 to 584 ng/L, P<.05) in response to hyperinsulinemia, whereas concurrent L/H infusion had no additional effect on ghrelin levels (584+/-67 vs 548+/-82 ng/L). In summary, we found that FFA induced hepatic insulin resistance, and to a lesser extent, peripheral insulin resistance was associated with elevated plasma resistin levels. We conclude that FFA-induced release of resistin may contribute to the development of FFA-induced insulin resistance in rats.
Yang
Gangyi
G
Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. yanggangyi@hotmail.com
Li
Ling
L
Fang
Chao
C
Zhang
Ling
L
Li
Qingming
Q
Tang
Yi
Y
Boden
Guenther
G
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000494:pharmacology*; D054439:Ghrelin; D015309:Glucose Clamp Technique; D006729:Hormones, Ectopic / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D036361:Peptide Hormones / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin; D014851:Wakefulness
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D006729:Hormones, Ectopic; D036361:Peptide Hormones; D052243:Resistin; C499622:Retn protein, rat