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Blunted Hepatic Glucose Production from Lactate in Leptin‐Treated Streptozotocin‐Induced Diabetic Rats
Author(s) -
Kang Yuan,
Wernette Catherine M.,
Judd Robert L.,
White B. Douglas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.856.4
Subject(s) - medicine , endocrinology , leptin , streptozotocin , gluconeogenesis , insulin , bicarbonate , chemistry , diabetes mellitus , metabolism , obesity
The aim of this study was to compare the hepatic glucose output of leptin‐ and vehicle‐treated diabetic rats in response to lactate via an isolated perfused liver system. Wistar rats were made diabetic with an IV injection of STZ (50 mg/kg). After confirmation of hyperglycemia, rats were administrated a daily ICV injection of either leptin (5 microgram/day) or vehicle. Once blood glucose concentrations of the leptin‐treated diabetic rats returned to normal, each rat was fasted and administered lactate (16.6 mmol/kg) via gastric gavage. Blood glucose concentrations were determined every 15 min for 2 hours. Rats were fasted as before and the livers perfused at a rate of 35 ml/min with Krebs‐Henseleit‐Bicarbonate (KHB) buffer for 30 min, followed by KHB buffer supplemented with lactate (2 mM) for one hour. Perfusates were collected in 30‐second fractions and glucose concentrations in selected fractions determined. Leptin‐treated rats had nearly a 5‐fold lower glucose response to lactate gavage than vehicle‐treated rats. Hepatic glucose production from the fasted leptin‐treated rats was also severely blunted as compared to vehicle‐treated rats. These data suggest that chronic leptin administration leads to an inhibition of gluconeogenesis, which may result in normalization of blood glucose concentration in STZ‐induced diabetic rats. (Supported by the Alabama Agricultural Experiment Station)