Brain-derived neurotrophic factor ameliorates hepatic insulin resistance in Zucker fatty rats

• Published in: Metabolism, clinical and experimental Vol. 52; no. 2; pp. 203 - 208
• Main Authors: Kuroda, Akio, Yamasaki, Yoshimitsu, Matsuhisa, Munehide, Kubota, Minoru, Nakahara, Itsuro, Nakatani, Yoshihisa, Hoshi, Ayumu, Gorogawa, Shin-ichi, Umayahara, Yutaka, Itakura, Yasushi, Nakagawa, Tsutomu, Taiji, Mutsuo, Kajimoto, Yoshitaka, Hori, Masatsugu
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2003; Elsevier
• Subjects: Animals; Associated diseases and complications; Biological and medical sciences; Blood Glucose - analysis; Brain-Derived Neurotrophic Factor - pharmacology; Carboxy-Lyases - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glucokinase - genetics; Glucose-6-Phosphatase - genetics; Glycogen - metabolism; Insulin - blood; Insulin Resistance; Liver - drug effects; Liver - physiopathology; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - physiopathology; Rats; Rats, Zucker; RNA, Messenger - metabolism; Endocrinopathy; Animal model; Prognosis; Rat; Phosphoric monoester hydrolases; Male; Esterases; Lyases; Hyperglycemia; Enzymatic activity; Carboxy-lyases; Subcutaneous administration; Brain derived neurotrophic factor; Nutritional status; Obesity; Enzyme; Transferases; Diabetes mellitus; Rodentia; Nutrition disorder; Experimental study; Insulin; Target tissue resistance; Carbon-carbon lyases; Vertebrata; Concomitant disease; Chemotherapy; Mammalia; Treatment; Animal; Glucokinase; Hydrolases; Glucose-6-phosphatase; Phosphoenolpyruvate carboxykinase (ATP)
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1053/meta.2003.50026

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophins, has been reported to ameliorate hyperglycemia in obese diabetic animal models. To elucidate the mechanism of BDNF on glucose metabolism, we determined the glucose turnover under basal and euglycemic hyperinsulinemic (insulin infusion rate, 54 pmol · kg−1 · min−1) clamp conditions in obese insulin-resistant rats, male Zucker fatty rats, which had been acutely administered a subcutaneous injection of BDNF (20 mg/kg) (n = 9, BDNF) or vehicle (n = 8, vehicle). Under the basal condition, acute administration of BDNF did not affect the blood glucose level, plasma insulin level, rate of glucose disappearance (Rd), and endogenous glucose production (EGP). Under the clamp condition, the glucose infusion rate (GIR) was significantly higher in BDNF than in vehicle (mean ± SD, 61.4 ± 19.1 v 41.4 ± 4.9 μmol · kg−1 · min−1, P <.05). There was no significant difference in Rd and EGP between the 2 groups under the clamp condition, but the insulin-mediated suppression ratio of endogenous glucose production in BDNF was significantly greater than in vehicle (48.9 ± 22.2 v 22.4% ± 20.6%, P <.05). In BDNF, mRNA expressions of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were comparable to those of vehicle, while hepatic glucokinase (GK) mRNA expression was significantly higher (1.57 ± 0.33 v 1.03 ± 0.17, P <.05). We conclude that BDNF mainly improves hepatic insulin resistance in obese insulin-resistant rats, probably by affecting the hepatic GK flux. Copyright 2003, Elsevier Science (USA). All rights reserved.