Insulin-like effect of low-dose leptin on glucose transport in Langendorff rat hearts.
BACKGROUND
In a murine myotube cell line (C 2 C 12 myotubes), leptin at low physiological concentrations (1 ng/ml) has been shown to stimulate glucose transport and glycogen synthesis. The aim of the present study was to test whether an analogous leptin effect on glucose transport is detectable in the heart.


RESULTS
We used the isolated Langendorff rat heart preparation with hemodynamic function control. Using polymerase chain reaction (RT-PCR), a 346- and 375-base fragment indicative for the short and long leptin receptor isoform was detected in the rat heart. Glucose transport rates were calculated using equimolar double tracer perfusion with the non-metabolizable glucose analog 3-O-methylglucose (3-O-MG) and the non-transportable tracer mannitol and two-compartimental modeling. 3-O-MG uptake at a perfusate glucose concentration of 11 mM was measured over 15 minutes in control hearts, hearts perfused with insulin (10 mU/ml), leptin (1 ng/ml) or insulin (10 mU/ml) plus leptin (1 ng/ml; n = 8 in each group). The basal 3-O-MG transport rate of 0,7351 +/- 0,051 micro mol/min/g wet weight was increased 4.18 fold with insulin, 2.69 fold with leptin, and 4.2 fold with leptin plus insulin. Simultaneous monitoring of hemodynamic function revealed a minor and transient effect of leptin on left ventricular pressure, which was strongly augmented in coperfusion with insulin.


CONCLUSIONS
The data suggest that leptin at low physiological concentrations is able to exert a partial insulin like effect on glucose uptake. We speculate that the effect might be mediated by both leptin receptor isoforms. This leptin effect is additive to the effect of insulin and might therefore contribute to the insulin independent basal glucose supply of the heart. It can not be completely excluded that the observed leptin effect on glucose transport is secondary to altered myocardial function.
Haap
M
M
Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University Tuebingen, Germany. mmhaap@med.uni-tuebingen.de
Houdali
B
B
Maerker
E
E
Renn
W
W
Machicao
F
F
Hoffmeister
H M
HM
Häring
H-U
HU
Rett
K
K
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin
D007328:Insulin; D020738:Leptin; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D005947:Glucose