Hypothalamic orexin expression: modulation by blood glucose and feeding

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 11; pp. 2132 - 2137
• Main Authors: CAI, X. J, WIDDOWSON, P. S, HARROLD, J, WILSON, S, BUCKINGHAM, R. E, ARCH, J. R. S, TADAYYON, M, CLAPHAM, J. C, WILDING, J, WILLIAMS, G
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-11-1999
• Subjects: Animals; Biological and medical sciences; Blood Glucose - physiology; Deoxyglucose - pharmacology; Diabetes Mellitus, Experimental - metabolism; Eating - physiology; Fasting - physiology; Feeding. Feeding behavior; Food Deprivation - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hyperphagia - metabolism; Hypoglycemia - chemically induced; Hypoglycemia - metabolism; Hypothalamic Area, Lateral - metabolism; Insulin - pharmacology; Intracellular Signaling Peptides and Proteins; Leptin - pharmacology; Male; Neurons - metabolism; Neuropeptides - genetics; Orexins; Protein Precursors - genetics; Rats; Rats, Sprague-Dawley; Rats, Wistar; Transcription, Genetic; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Feeding behavior; Peptides; Rat; Rodentia; Central nervous system; Glucose; Hypothalamus; Gene expression; Vertebrata; Mammalia; Metabolic precursor; Restricted diet; Nutritional status; Glycemia; Brain (vertebrata)
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.11.2132

Hypothalamic orexin expression: modulation by blood glucose and feeding.
X J Cai ,
P S Widdowson ,
J Harrold ,
S Wilson ,
R E Buckingham ,
J R Arch ,
M Tadayyon ,
J C Clapham ,
J Wilding and
G Williams
Department of Medicine, University of Liverpool, UK.
Abstract
Orexins (hypocretins), novel peptides expressed in specific neurons of the lateral hypothalamic area (LHA), stimulate feeding
when injected intracerebroventricularly. We investigated their role in feeding in the rat by measuring hypothalamic prepro-orexin
mRNA levels under contrasting conditions of increased hunger. Prepro-orexin mRNA levels increased significantly after 48 h
of fasting (by 90-170%; P < 0.05) and after acute (6 h) hypoglycemia when food was withheld (by 90%; P < 0.02). By contrast,
levels were unchanged during chronic food restriction, streptozotocin-induced diabetes, hypoglycemia when food was available,
voluntary overconsumption of palatable food, or glucoprivation induced by systemic 2-deoxy-D-glucose. Orexin expression was
not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose
in the absence of food. Orexins may participate in the short-term regulation of energy homeostasis by initiating feeding in
response to falls in glucose and terminating it after food ingestion. The LHA is known to contain neurons that are stimulated
by falls in circulating glucose but inhibited by feeding-related signals from the viscera; orexin neurons may correspond to
this neuronal population.