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Low Plasma Leptin Levels Contribute to Diabetic Hyperphagia in Rats
Date
1999-06Author
Sindelar, Dana K.
Havel, Peter J.
Seeley, Randy J.
Wilkinson, Charlew W.
Woods, Stephen C.
Schwartz, Michael W.
Metadata
Show full item recordAbstract
The adipocyte hormone leptin reduces food intake in
normal animals. During uncontrolled type 1 diabetes,
plasma leptin levels fall, whereas food intake increases.
To test the hypothesis that low leptin levels
contribute to diabetic hyperphagia, we investigated the
e ffect on food intake of replacement of leptin at basal
plasma concentrations for 7 days in Long-Evans rats
with uncontrolled diabetes induced by streptozotocin
(STZ). One group of STZ diabetic rats received saline
(STZ + Sal) (n = 11), while the other group (STZ +
Lep) (n = 15) received a subcutaneous infusion of
recombinant rat leptin (100 μg ? k g– 1 ? d a y– 1) via
osmotic minipumps. A nondiabetic control group (Con)
(n = 11) received saline only. In the STZ + Sal group,
plasma leptin levels decreased by 75% (P < 0.05) from
2.4 ± 0.5 on the day before STZ/citrate buffer vehicle
( Veh) injection (day 0) to 0.6 ± 0.2 ng/ml on day 7. In
contrast, plasma leptin levels on days 3–7 were comparable
to pretreatment values in both the STZ + Lep
group (day 0: 2.6 ± 0.4 vs. day 7: 2.5 ± 0.3 ng/ml, NS) and
the Con group (day 0: 3.8 ± 0.4 vs. day 7: 2.9 ±
1.0 ng/ml, NS). In the STZ + Sal group, daily food intake
increased gradually to values 43% above basal by day 7
(day 0: 24 ± 2 to day 7: 33 ± 3 g, P < 0.05), whereas food
intake did not increase in either the STZ + Lep group
(day 0: 24 ± 1 vs. day 7: 21 ± 2 g, NS), or the Con group
(day 0: 23 ± 1 vs. day 7: 23 ± 2 g). Plasma glucose levels
exceeded nondiabetic control values (7.7 ±
0.2 mmol/l) in both diabetic groups, but were lower in
the STZ + Lep group (17.2 ± 1.8 mmol/l) than in the STZ
+ Sal group (24.3 ± 1.1 mmol/l, P < 0.05). To determine
if sensitivity to leptin-induced anorexia was affected by
STZ treatment, a second experiment was performed in
which the effect of intracerebroventricular leptin injection
(at doses of 0.35, 1.0, or 3.5 μg) on food intake was
measured 10 days after STZ or Veh treatment. Leptin
suppressed both 4- and 24-h food intake in the two
groups to an equal extent at every dose (by 15, 22, and
35%, respectively). These findings support the hypothesis
that the effect of uncontrolled diabetes to lower
leptin levels contributes to diabetic hyperphagia and
that this effect is not due to altered leptin sensitivity.
D i a b e t e s 48:1275–1280, 1999