Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat.
Galanin-like peptide (GALP) is produced in a small population of neurons in the arcuate nucleus of the hypothalamus, and leptin stimulates the hypothalamic expression of GALP mRNA. Because insulin and leptin share common signaling pathways in the brain, we reasoned that GALP neurons might also be responsive to changes in circulating concentrations of insulin. To test this hypothesis, we first studied the effect of insulin deficiency on the expression of GALP by comparing levels of GALP mRNA between normal and diabetic animals. Streptozotocin-induced diabetes was associated with a significant reduction in the expression of GALP mRNA, which was reversed by treatment with either insulin or leptin. Second, we examined the effect of insulin administered directly into the brain on the expression of GALP mRNA in fasted rats. Hypothalamic levels of GALP mRNA were lower in animals after a 48-h fast, and central treatment with insulin reversed this effect. These results suggest that GALP neurons are direct targets for regulation by insulin and implicate these cells for a role in the metabolic and behavioral sequelae of type 1 diabetes.
Fraley
Gregory S
GS
Department of Physiology & Biophysics, University of Washington School of Medicine, 1959 NE Pacific Street, HSB G-424, Seattle, WA 98195-7290, USA.
Scarlett
Jarrad M
JM
Shimada
Issei
I
Teklemichael
Dawit N
DN
Acohido
Blake V
BV
Clifton
Donald K
DK
Steiner
Robert A
RA
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D044089:Galanin-Like Peptide / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020542:Third Ventricle; D013997:Time Factors
D044089:Galanin-Like Peptide; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger