| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita, 879-5593 Japan
3Correspondence: Department of Internal Medicine I, School of Medicine, Oita Medical University, Idaigaoka, Hasama, Oita, 879-5593 Japan. E-mail: SAKATA{at}oita-med.ac.jp
We examined the effects of chronic centrally administered leptin on the glucose metabolism of streptozotocin-induced diabetic (STZ-D) rats, a model for insulin-dependent diabetes mellitus. When 3 µg ·rat-1 · day-1 of leptin was infused into the third ventricle for 6 consecutive days (STZ-LEP), STZ-D rats became completely euglycemic. The effect was not seen when the same dosage was administered s.c. Centrally administered leptin did not affect peripheral insulin levels. The feeding volume of STZ-LEP rats was suppressed to the level of non-STZ-D control rats. No improvement of hyperglycemia was noted when STZ-D rats were pair-fed to match the feeding volume of STZ-LEP rats. Thus, the euglycemia of STZ-LEP rats cannot be due to the decreased feeding volume. In the STZ-D rat, glucokinase mRNA, a marker of glycolysis, is down-regulated whereas glucose-6-phosphatase mRNA, a marker of gluconeogenesis, and glucose transporter (GLUT) 2, which is implicated in the release of glucose from liver, are up-regulated. GLUT4, uncoupling protein (UCP) 1, and UCP3 were down-regulated in brown adipose tissue. These parameters returned to normal upon central infusion of leptin. GLUT4 was not down-regulated in the skeletal muscle of STZ-D rats; however, fatty acid binding protein and carnitine palmitoyltransferase I, markers for utilization and ß-oxidation of fatty acids, were up-regulated and restored when the rats were treated with leptin. The increase and subsequent decrease of fatty acid utilization suggests a decrease of glucose uptake in the skeletal muscle of STZ-D rats, which was restored upon central leptin administration. We conclude that centrally infused leptin does not control serum glucose by regulating feeding volume or elevating peripheral insulin, but by regulating hepatic glucose production, peripheral glucose uptake, and energy expenditure. The present study indicates the possibility of future development of a new class of anti-diabetic agents that act centrally and independent of insulin action.—Hidaka, S., Yoshimatsu, H., Kondou, S., Tsuruta, Y., Oka, K., Noguchi, H., Okamoto, K., Sakino, H., Teshima, Y., Okeda, T., Sakata, T. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats.
Key Words: STZ-induced insulin-deficient diabetes • glucose transporters • uncoupling proteins • anti-diabetic drugs
This article has been cited by other articles:
|
|
 |
|
  X. Yu, B.-H. Park, M.-Y. Wang, Z. V. Wang, and R. H. Unger Making insulin-deficient type 1 diabetic rodents thrive without insulin PNAS, September 16, 2008; 105(37): 14070 - 14075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, C. M Wernette, R. L Judd, K. W Huggins, and B D. White Guanethidine treatment does not block the ability of central leptin administration to decrease blood glucose concentrations in streptozotocin-induced diabetic rats J. Endocrinol., September 1, 2008; 198(3): 541 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Housley, J. T. Rodgers, N. D. Udeshi, T. J. Kelly, J. Shabanowitz, D. F. Hunt, P. Puigserver, and G. W. Hart O-GlcNAc Regulates FoxO Activation in Response to Glucose J. Biol. Chem., June 13, 2008; 283(24): 16283 - 16292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. da Silva, L. S. Tallam, J. Liu, and J. E. Hall Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1275 - R1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tanaka, S. Hidaka, H. Masuzaki, S. Yasue, Y. Minokoshi, K. Ebihara, H. Chusho, Y. Ogawa, T. Toyoda, K. Sato, et al. Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation Parallels Metabolic Phenotype in Leptin Transgenic Mice Under Dietary Modification Diabetes, August 1, 2005; 54(8): 2365 - 2374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gutierrez-Juarez, S. Obici, and L. Rossetti Melanocortin-independent Effects of Leptin on Hepatic Glucose Fluxes J. Biol. Chem., November 26, 2004; 279(48): 49704 - 49715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Lam, J. T. Lewis, A. T. Cheung, C. T. Luk, J. Tse, J. Wang, M. Bryer-Ash, J. K. Kolls, and T. J. Kieffer Leptin Increases Hepatic Insulin Sensitivity and Protein Tyrosine Phosphatase 1B Expression Mol. Endocrinol., June 1, 2004; 18(6): 1333 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. da Silva, J. J. Kuo, and J. E. Hall Role of Hypothalamic Melanocortin 3/4-Receptors in Mediating Chronic Cardiovascular, Renal, and Metabolic Actions of Leptin Hypertension, June 1, 2004; 43(6): 1312 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Fraley, J. M. Scarlett, I. Shimada, D. N. Teklemichael, B. V. Acohido, D. K. Clifton, and R. A. Steiner Effects of Diabetes and Insulin on the Expression of Galanin-Like Peptide in the Hypothalamus of the Rat Diabetes, May 1, 2004; 53(5): 1237 - 1242. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
