title: Chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport.
abstract: Leptin, the product of the ob gene, has been shown to reduce fat mass, food intake, hyperglycemia, and hyperinsulinemia and to increase whole-body glucose disposal. However, it is unknown if leptin improves insulin action in skeletal muscle. Therefore, the purpose of this investigation was to determine if chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Sixty-nine female Sprague-Dawley rats (240 to 250 g) were randomly assigned to one of three groups: (1) control, (2) pair-fed, and (3) leptin. All animals were subcutaneously implanted with miniosmotic pumps that delivered 0.5 mg leptin/kg/d to the leptin animals and vehicle to the control and pair-fed animals for 14 days. Following this 14-day period, all animals were subjected to hindlimb perfusion to determine the rates of skeletal muscle glucose uptake and 3-O-methyl-D-glucose (3-MG) transport under basal, submaximal (500 microU/mL), and maximal (10,000 microU/mL) insulin concentrations. Chronic leptin treatment significantly increased (P < .05) the rate of glucose uptake across the hindlimb by 27%, 32%, and 47% under basal, submaximal, and maximal insulin, respectively, compared with the control and pair-fed condition. However, when the submaximal rate of glucose uptake was expressed as a percentage of maximal insulin-stimulated glucose uptake, no differences existed among the groups, indicating that leptin treatment does not increase insulin sensitivity. Rates of 3-MG transport in the soleus, plantaris, and white and red portions of the gastrocnemius (WG and RG) were significantly increased (P < .05) in leptin animals under all perfusion conditions. 3-MG transport was not different between control and pair-fed animals. Collectively, these findings suggest that improvements in insulin-stimulated skeletal muscle glucose uptake and transport following chronic leptin treatment result from increased insulin responsiveness.
authors.affiliation: Department of Kinesiology, California State University Northridge 91330-8287, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Yaspelkis
authors.forename: L
authors.initials: L
authors.lastname: Ansari
authors.forename: E L
authors.initials: EL
authors.lastname: Ramey
authors.forename: G J
authors.initials: GJ
authors.lastname: Holland
authors.forename: S F
authors.initials: SF
authors.lastname: Loy
mesh_terms: D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007328:Insulin; D020738:Leptin; D011506:Proteins; D019325:3-O-Methylglucose; D005947:Glucose