Kazuo Kurata

D-glucose suppression of eating after intra-third ventricle infusion in rat

To clarify the hypophagic action of D-glucose, meal size, postprandial intermeal interval and eating rate were analyzed after infusion of glucose into the third cerebroventricle. The effects of glucose structure modification on feeding modulation were examined by comparing the effects of glucose to those of its epimers, D-mannose, D-allose and D-galactose. Glucose, infused in doses of 6 to 24 mumol, dose relatedly reduced meal size, but did not change other meal parameters. The minimum dose of glucose to induce feeding suppression was between three and 6 mumol. The epimers, at doses of 24 mumol, did not affect food intake or body weight. Drinking patterns and ambulatory activity were not changed by glucose infusion. These findings were consistent with neuronal activity observed in the ventromedial hypothalamic nucleus.

Charting of Daily Weight Pattern Reinforces Maintenance of Weight Reduction in Moderately Obese Patients

To maintain reduced body weight by behavioral therapy in moderately obese patients, body weight was measured four times daily and charted in a weekly graph. Seventy-two female patients with simple obesity were divided into two groups: 55 patients with appliance of charting of weight pattern (group-I), and 17 patients without the charting (group-II). The percentage of patients followed for 2 years was different between group-I (87%) and group-II (65%) during 2 years after completion of weight reduction therapy interviews (p less than 0.05). Forty-eight of group-I patients succeeded in decreasing their weight by 15.2 +/- 1.5 (mean +/- SEM) kg during the 6.5 +/- 0.8 months of the therapy interviews. They were followed up for 3.8 years with no rebound weight gain. Eleven patients in group-II also succeeded in decreasing their weight by 16.8 +/- 1.9 kg during 7.8 +/- 1.3 months but their body weight rebounded by 9.0 kg during the 2-year followup period. Twelve of 15 male patients with weight charting maintained reduced weight during 4.3 years. It was easier and more effective for obese patients to maintain weight graphs for the longer period than to record no weight graphs. Obese patients could themselves monitor irregular weight patterns produced by overeating and correct the irregularities in food intake and daily lifestyles. This seems to explain why the illustration of daily fluctuations of weight measurements was useful for long-term maintenance of weight reduction.

Administration of D-glucosamine into the third cerebroventricle induced feeding accompanied by hyperglycemia in rats.

D-glucosamine, 2-amino-2-deoxy-D-glucose, is known to be an endogenous glucose analogue and to antagonize glucose uptake and metabolism. The present experiments were aimed to clarify effects of glucosamine and related chemical substances on ingestive behavior, as well as its direct effects on hypothalamic neurons. Infusion of 24 mumole glucosamine into the third cerebroventricle induced feeding within 30 min in 5 rats out of 7 tested, accompanied by increased ambulatory activity. No periprandial drinking was observed. Plasma glucose level increased, peaking at 30 min after the injection. Plasma insulin level tended to increase, but not significantly. Electrophoretic application of glucosamine activated glucose-sensitive neurons in the lateral hypothalamus and suppressed glucoreceptors in the ventromedial hypothalamus. These facts, together with other reported results, suggest that glucosamine can modulate physiological feeding and that carbon 2 of the glucose molecule is important in feeding modulation by glucose analogues.

Structural evaluation of glucose analogues on feeding elicitation in rat

The effects of 12-mumol doses of the glucose analogues glucosamine, 2-fluoroglucose, 2-chloroglucose, 2-deoxyglucose (which were modified at carbon 2 of the glucopyranose ring), 1-aminoglucose and 1-deoxyglucose (modified at carbon 1), on feeding behavior and plasma glucose, insulin, and glycerol were examined after infusion into the rat third cerebroventricle. Plasma glucose and glycerol levels were elevated by glucosamine or 1-aminoglucose. Plasma insulin levels were unchanged by these analogues. Feeding was induced in 62% to 87% of the rats tested after infusion of glucosamine, 2-fluoroglucose, 2-chloroglucose, 2-deoxyglucose, 1-aminoglucose, or 1-deoxyglucose (mean meal size in responding rats, 43.9, 25.8, 22.7, 16.0, 42.3, and 3.8 pellets, respectively). The order of potency to induce feeding was amino, halogen, and hydrogen groups. These data reinforced the concept that the potency of glucose analogues to induce feeding depends on substituents at carbon 1 and carbon 2 of the glucopyranose ring.

Differential Mechanisms of Feeding Modulation Induced by Amino Sugars in Rats

Abstract The present study examined and compared the effects of N-acetylglucosamine and 1-deoxy-N-acetylglucosamine on feeding behavior with those of glucosamine and 1-deoxyglu-cosamine. Infusion of 12 μmole N-acetylglucosamine and 24 μmole 1-deoxy-N-acetylglucosamine into the rat third cerebroventricle did not affect the feeding behavior. However, oral administration of 1200 μmole N-acetylglucosamine elicited feeding and 2400 μmole 1-deoxy-N-acetylglucosamine markedly suppressed feeding. These effects were abolished by truncal vagotomy. Both glucosamine and 1-deoxyglucosamine affected feeding by intra-third cerebroventricular and oral administration. These findings indicate that N-acetyl amino sugars modulate feeding behavior peripherally through the vagal afferent nerve.

Characteristics of psychomotor performance and time cognition in moderately obese patients

To clarify adherence of obese subjects to external food-relevant stimuli, we examined time cognition and psychomotor functioning of the obese under noneating conditions in the present study. Matched on the basis of age, sex, height, intelligence quotient and education, 13 moderately, but adult-onset obese (mean obesity index +/- SEM, 53.9 +/- 5.0% by Matsukis method) and 13 normal weight subjects (-6.3 +/- 2.3%) were tested. Obese females were slower than normal weight control subjects in alternate tapping of two metal plates (p less than 0.01) and in transfer of a dowel (p less than 0.05). Normal subjects were slightly but significantly (p less than 0.05) more efficient in a self-cued traverse movement test, whereas the obese subjects were very much less efficient in the self-cued than in the externally-cued test. These findings suggest that evaluation of deficits of the obese must consider other factors in addition to simple physical slowness due to fattening. In time cognition tests, cognitive levels of the obese were more accurate when initiated by time cues than when they were self-cued (p less than 0.01). The results indicate that obese (even after adult-onset) may exhibit impairment in internal time cognition when deprived of external modulating time cues.

Structural characteristics of endogenous sugar acids and relations to feeding modulation.

Structural specificity among short-chain organic acids for effects on feeding behavior, blood glucose and insulin was investigated by infusion of 1 exogenous and 6 endogenous derivatives into the rat third cerebral ventricle. Glyceric acid (GEA) (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 3,4,5-trihydroxypentanoic acid gamma-lactone (3,4,5-TP) (2.50 mumol) decreased food intake for, at most, 24 h. These acids depressed the size of the first meal after infusion, but did not affect latency to the first meal, eating speed, drinking or ambulation. Infusion of 2,4-dihydroxybutanoic acid gamma-lactone (2,4-DB) (1.25 mumol), 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP), and an exogenous compound, 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2,4,5,6-TH) (2.50 mumol), induced transient initial feeding which was not necessarily accompanied by periprandial drinking. Ambulation was concomitantly increased. Of these organic acids, 3,4-DB and 2,4,5-TP were most potent in their effects on feeding. Hyperglycemia was induced by 2.50 mumol 3,4-DB leaving insulin unaffected; 2.50 mumol 2,4,5-TP caused hypoglycemia, with a persistent but not significant rise in insulin. The results suggest that slight structural differences of endogenous organic acids, in particular the positions of hydroxyl groups on the lactone ring of 4-butanolide, may be important in feeding modulation by conveying intrinsically reciprocal signals to neurons involved in feeding and satiety.

Effect of an amino group at carbon 2 of 1-deoxyglucose analogues on anorexia in the rat

A steric hindering group at carbon 2 of 1-deoxyglucose analogues was introduced by epimerization, deoxidation and substitution of a hydroxyl group with either an acetamido or a fluoro group. Injection of this analogue into the rat third cerebroventricle attenuated the feeding suppression produced by 1-deoxyglucose. In contrast, the replacement of a hydroxyl group at carbon 2 with an amino group produced anorexia of the same magnitude as that produced by 1-deoxyglucose. Amination at carbon 2 was more potent than that at carbon 3, 4 or 6. These results indicate that an amino group at carbon 2 of the glucose molecule is important to reinforce the feeding suppression caused by 1-deoxyglucose analogues.