title: Acute hyperleptinemia does not modify insulin sensitivity in vivo in the rat.
abstract: Insulin resistance is associated with hyperleptinemia, whilst exposure of hepatoma cells and isolated adipocytes to high concentrations of leptin has been demonstrated to result in attenuated insulin response and a reduced suppression of gluconeogenesis. To determine the acute metabolic effects of hyperleptinemia, we measured whole body glucose uptake (WBU) and hepatic glucose production rate (HGP) in rats using the euglycemic hyperinsulinemic clamping technique. Anesthetised male rats received recombinant murine leptin (1 microg/min) or vehicle into the jugular vein for 90 min. After 30 min of leptin infusion, insulin was infused to a level of 70 microU/ml and a variable-rate glucose infusion was adjusted to maintain blood glucose levels to 4-4.5 mmol/l. Glucose infusion rates during clamping were not different between leptin-infused and control rats, and there were no significant effects on the HPR or WBU measured using [6-(3)H]glucose under basal or clamped conditions. In summary, our data demonstrate that acute hyperleptinemia in normal weight Wistar rats does not appear to reduce insulin sensitivity, in vivo, or to affect HPR under clamp conditions.
authors.affiliation: Department of Medicine, Liverpool University, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Widdowson
authors.forename: R
authors.initials: R
authors.lastname: Upton
authors.forename: L
authors.initials: L
authors.lastname: Pickavance
authors.forename: R
authors.initials: R
authors.lastname: Buckingham
authors.forename: M
authors.initials: M
authors.lastname: Tadayyon
authors.forename: J
authors.initials: J
authors.lastname: Arch
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000378:metabolism*; D007333:Insulin Resistance; D020738:Leptin; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001786:Blood Glucose; D020738:Leptin; D011506:Proteins; D005947:Glucose