Role of the glucopyranose ring in the elicitation of feeding.
To relate the structural characteristics of the glucose pyranose ring to feeding elicitation, biochemically and structurally similar glucose analogues were investigated to determine if they could elicit short- or long-term effects on food intake in rats. Testing solutions were infused once into unrestrained and unanesthetised rats through a chronically indwelling cannula in the third ventricle. D-Glucose markedly decreased meal size in doses from 6 to 24 mumol, but it's epimers, D-mannose, D-allose and D-galactose, did not affect food intake. Among the glucose analogues modified at C-2, rats treated with 12 mumol D-glucosamine ate a much larger size of meal than those with 12 mumol halogenglucoses or 24 mumol 2-deoxy-D-glucose, while 2-fluoro-2-deoxy-D-glucose with 2-chloro-2-deoxy-D-glucose induced a more potent feeding than 2-deoxyglucose. Glucosamine also induced hyperglycaemia, but did not affect plasma insulin. Activity of glucose, sensitive neurons in the lateral hypothalamus was increased by electro-osmotic application of 2-deoxyglucose or glucosamine, and the reciprocity was observed on neurons of the ventromedial hypothalamus. One-aminoglucose (beta-D-glucopyranosylamine), which is an aminoglucose analogue modified on C-1, increased meal size and more potently prolonged the duration of the meal compared to 1-deoxyglucose (1,5-anhydroglucitol). Together with the behavioural and structural characteristics of glucose analogues, a hydroxyl group on C-1 or C-2 is involved in feeding elicitation. The magnitude of the effect can be partly explained by the chemical concept of 'inductive effect'.
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
T
T
Sakata
K
K
Fujimoto
K
K
Kurata
H
H
Etou
K
K
Fukagawa
Y
Y
Okabe
K
K
Ookuma
D000818:Animals; D004435:Eating / Q000187:drug effects*; D005947:Glucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D005947:Glucose