Diabetes, Vol 48, Issue 2 287-291, Copyright © 1999 by American Diabetes Association

ARTICLES

Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats

Y Minokoshi, MS Haque and T Shimazu
Department of Medical Biochemistry, Ehime University School of Medicine, Japan. minokosh@m.ehime-u.ac.jp

We studied the effects of microinjection of leptin into the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) on glucose uptake in peripheral tissues in unanesthetized rats. The rate of glucose uptake was assessed in vivo by 2-[3H]deoxyglucose incorporation. Single injection of leptin into VMH increased glucose uptake in brown adipose tissue (BAT), heart, skeletal muscles, and spleen but not in white adipose tissue or skin. On the other hand, microinjection of leptin into LH had little effect on glucose uptake in those tissues. The plasma concentrations of glucose and insulin were unaltered by intrahypothalamic injection of leptin into either VMH or LH. Among skeletal muscles, the increase in glucose uptake induced by intrahypothalamic injection of leptin was greater in the soleus than in the extensor digitorum longus. Likewise, the increased glucose uptake in the gastrocnemius in response to leptin was more prominent in the red part than in the white part of the tissue. When surgical sympathetic denervation of the interscapular BAT was performed, the enhanced glucose uptake by BAT in response to intrahypothalamic leptin was completely suppressed. These findings suggest that intrahypothalamic injection of leptin preferentially increases glucose uptake by some peripheral tissues through activation of the VMH-sympathetic (or its neighboring medial hypothalamus-sympathetic) nervous system, thereby contributing to the maintenance of energy balance.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. J. Morton Hypothalamic leptin regulation of energy homeostasis and glucose metabolism J. Physiol., September 1, 2007; 583(2): 437 - 443. [Abstract] [Full Text] [PDF]

				M Mitchell, D T Armstrong, R L Robker, and R J Norman Adipokines: implications for female fertility and obesity Reproduction, November 1, 2005; 130(5): 583 - 597. [Abstract] [Full Text] [PDF]

				S. R. Ladyman and D. R. Grattan Suppression of Leptin Receptor Messenger Ribonucleic Acid and Leptin Responsiveness in the Ventromedial Nucleus of the Hypothalamus during Pregnancy in the Rat Endocrinology, September 1, 2005; 146(9): 3868 - 3874. [Abstract] [Full Text] [PDF]

				T. Alquier and B. B. Kahn Peripheral Signals Set the Tone for Central Regulation of Metabolism Endocrinology, September 1, 2004; 145(9): 4022 - 4024. [Full Text] [PDF]

				A. Kalsbeek, S. La Fleur, C. Van Heijningen, and R. M. Buijs Suprachiasmatic GABAergic Inputs to the Paraventricular Nucleus Control Plasma Glucose Concentrations in the Rat via Sympathetic Innervation of the Liver J. Neurosci., September 1, 2004; 24(35): 7604 - 7613. [Abstract] [Full Text] [PDF]

				C. Perrin, C. Knauf, and R. Burcelin Intracerebroventricular Infusion of Glucose, Insulin, and the Adenosine Monophosphate-Activated Kinase Activator, 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside, Controls Muscle Glycogen Synthesis Endocrinology, September 1, 2004; 145(9): 4025 - 4033. [Abstract] [Full Text] [PDF]

				I. Leclerc, W. W. Woltersdorf, G. da Silva Xavier, R. L. Rowe, S. E. Cross, G. S. Korbutt, R. V. Rajotte, R. Smith, and G. A. Rutter Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E1023 - E1031. [Abstract] [Full Text] [PDF]

				C. Perez, C. Fernandez-Galaz, T. Fernandez-Agullo, C. Arribas, A. Andres, M. Ros, and J. M. Carrascosa Leptin Impairs Insulin Signaling in Rat Adipocytes Diabetes, February 1, 2004; 53(2): 347 - 353. [Abstract] [Full Text]

				R. Burcelin, M. Uldry, M. Foretz, C. Perrin, A. Dacosta, M. Nenniger-Tosato, J. Seydoux, S. Cotecchia, and B. Thorens Impaired Glucose Homeostasis in Mice Lacking the {alpha}1b-Adrenergic Receptor Subtype J. Biol. Chem., January 9, 2004; 279(2): 1108 - 1115. [Abstract] [Full Text] [PDF]

				A. J. Marsh, M. A.P. Fontes, S. Killinger, D. B. Pawlak, J. W. Polson, and R. A.L. Dampney Cardiovascular Responses Evoked by Leptin Acting on Neurons in the Ventromedial and Dorsomedial Hypothalamus Hypertension, October 1, 2003; 42(4): 488 - 493. [Abstract] [Full Text] [PDF]

				J. Y. Jeon, V. J. Harber, and R. D. Steadward Leptin response to short-term fasting in sympathectomized men: role of the SNS Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E634 - E640. [Abstract] [Full Text] [PDF]

				J. Y. Jeon, R. D. Steadward, G. D. Wheeler, G. Bell, L. McCargar, and V. Harber Intact Sympathetic Nervous System Is Required for Leptin Effects on Resting Metabolic Rate in People with Spinal Cord Injury J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 402 - 407. [Abstract] [Full Text] [PDF]

				R. B. CEDDIA, H. A. KOISTINEN, J. R. ZIERATH, and G. SWEENEY Analysis of paradoxical observations on the association between leptin and insulin resistance FASEB J, August 1, 2002; 16(10): 1163 - 1176. [Abstract] [Full Text] [PDF]

				S. HIDAKA, H. YOSHIMATSU, S. KONDOU, Y. TSURUTA, K. OKA, H. NOGUCHI, K. OKAMOTO, H. SAKINO, Y. TESHIMA, T. OKEDA, et al. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats FASEB J, April 1, 2002; 16(6): 509 - 518. [Abstract] [Full Text] [PDF]

				R. Burcelin, V. Crivelli, A. Dacosta, A. Roy-Tirelli, and B. Thorens Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E834 - E842. [Abstract] [Full Text] [PDF]

				S. U. Devaskar, R. Anthony, and W. Hay Jr. Ontogeny and insulin regulation of fetal ovine white adipose tissue leptin expression Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R431 - R438. [Abstract] [Full Text] [PDF]

				A. M. Madiehe, L. Lin, C. White, H. D. Braymer, G. A. Bray, and D. A. York Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R2048 - R2058. [Abstract] [Full Text] [PDF]

				G. Sweeney, J. Keen, R. Somwar, D. Konrad, R. Garg, and A. Klip High Leptin Levels Acutely Inhibit Insulin-Stimulated Glucose Uptake without Affecting Glucose Transporter 4 Translocation in L6 Rat Skeletal Muscle Cells Endocrinology, November 1, 2001; 142(11): 4806 - 4812. [Abstract] [Full Text] [PDF]

				T. Shiuchi, H. Nakagami, M. Iwai, Y. Takeda, T.-X. Cui, R. Chen, Y. Minokoshi, and M. Horiuchi Involvement of Bradykinin and Nitric Oxide in Leptin-Mediated Glucose Uptake in Skeletal Muscle Endocrinology, February 1, 2001; 142(2): 608 - 612. [Abstract] [Full Text] [PDF]

				J. R. Levy, J. Lesko, R. J. Krieg Jr., R. A. Adler, and W. Stevens Leptin responses to glucose infusions in obesity-prone rats Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1088 - E1096. [Abstract] [Full Text] [PDF]

				V. A. Boundy and A. H. Cincotta Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R505 - R514. [Abstract] [Full Text] [PDF]

				K. Matsumura, I. Abe, T. Tsuchihashi, and M. Fujishima Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1314 - R1320. [Abstract] [Full Text] [PDF]

				A. H. Cincotta, S. Luo, Y. Zhang, Y. Liang, K. G. Bina, T. L. Jetton, and P. W. D. Scislowski Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2000; 278(2): R435 - R444. [Abstract] [Full Text] [PDF]

				J. E. Schneider and D. Zhou Interactive effects of central leptin and peripheral fuel oxidation on estrous cyclicity Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R1020 - R1024. [Abstract] [Full Text] [PDF]

				P. T. Schwartz, B. Perez-Villamil, A. Rivera, R. Moratalla, and M. Vallejo Pancreatic Homeodomain Transcription Factor IDX1/IPF1 Expressed in Developing Brain Regulates Somatostatin Gene Transcription in Embryonic Neural Cells J. Biol. Chem., June 16, 2000; 275(25): 19106 - 19114. [Abstract] [Full Text] [PDF]