Perspectives in diabetes -: Insulin signaling in the central nervous system -: A critical role in metabolic homeostasis and disease from C-elegans to humans

被引:232
作者
Porte, D
Baskin, DG
Schwartz, MW
机构
[1] VA San Diego Hlth Care Syst, La Jolla, CA 92161 USA
[2] Univ Calif San Diego, Div Metab Diabet & Endocrinol, San Diego, CA 92103 USA
[3] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA
[4] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA
[5] Harborview Med Ctr, Seattle, WA USA
关键词
D O I
10.2337/diabetes.54.5.1264
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Insulin and its signaling systems are implicated in both central and peripheral mechanisms governing the ingestion, distribution, metabolism, and storage of nutrients in organisms ranging from worms to humans. Input from the environment regarding the availability and type of nutrients is sensed and integrated with humoral information (provided in part by insulin) regarding the sufficiency of body fat stores. In response to these afferent inputs, neuronal pathways are activated that influence energy flux and nutrient metabolism in the body and ensure reproductive competency. Growing evidence supports the hypothesis that reduced central nervous system insulin signaling from either defective secretion or action contributes to the pathogenesis of common metabolic disorders, including diabetes and obesity, and may therefore help to explain the close association between these two disorders. These considerations implicate insulin action in the brain, an organ previously considered to be insulin independent, as a key determinant of both glucose and energy homeostasis.
引用
收藏
页码:1264 / 1276
页数:13
相关论文
共 109 条
[1]   Insulin and leptin combine additively to reduce food intake and body weight in rats [J].
Air, EL ;
Benoit, SC ;
Clegg, DJ ;
Seeley, RJ ;
Woods, SC .
ENDOCRINOLOGY, 2002, 143 (06) :2449-2452
[2]   ALTERNATIVE PATHWAY OF INSULIN SIGNALING IN MICE WITH TARGETED DISRUPTION OF THE IRS-1 GENE [J].
ARAKI, E ;
LIPES, MA ;
PATTI, ME ;
BRUNING, JC ;
HAAG, B ;
JOHNSON, RS ;
KAHN, CR .
NATURE, 1994, 372 (6502) :186-190
[3]   IMMUNOCYTOCHEMICAL DETECTION OF INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) IN RAT-BRAIN - COLOCALIZATION WITH PHOSPHOTYROSINE [J].
BASKIN, DG ;
SIPOLS, AJ ;
SCHWARTZ, MW ;
WHITE, MF .
REGULATORY PEPTIDES, 1993, 48 (1-2) :257-266
[4]   STAT3 signalling is required for leptin regulation of energy balance but not reproduction [J].
Bates, SH ;
Stearns, WH ;
Dundon, TA ;
Schubert, M ;
Tso, AWK ;
Wang, YP ;
Banks, AS ;
Lavery, HJ ;
Haq, AK ;
Maratos-Flier, E ;
Neel, BG ;
Schwartz, MW ;
Myers, MG .
NATURE, 2003, 421 (6925) :856-859
[5]   The role of leptin→STAT3 signaling in neuroendocrine function:: an integrative perspective [J].
Bates, SH ;
Myers, MG .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2004, 82 (01) :12-20
[6]   Gut hormone PYY3-36 physiologically inhibits food intake [J].
Batterham, RL ;
Cowley, MA ;
Small, CJ ;
Herzog, H ;
Cohen, MA ;
Dakin, CL ;
Wren, AM ;
Brynes, AE ;
Low, MJ ;
Ghatei, MA ;
Cone, RD ;
Bloom, SR .
NATURE, 2002, 418 (6898) :650-654
[7]  
Benoit SC, 2002, J NEUROSCI, V22, P9048
[8]   Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size [J].
Blevins, JE ;
Schwartz, MW ;
Baskin, DG .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2004, 287 (01) :R87-R96
[9]   Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin [J].
Blevins, JE ;
Eakin, TJ ;
Murphy, JA ;
Schwartz, MW ;
Baskin, DG .
BRAIN RESEARCH, 2003, 993 (1-2) :30-41
[10]   Extended longevity in mice lacking the insulin receptor in adipose tissue [J].
Blüher, M ;
Kahn, BB ;
Kahn, CR .
SCIENCE, 2003, 299 (5606) :572-574