Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats

Malabu, Usman H.; McCarthy, H. D.; McKibbin, P.E.; Williams, Gareth

doi:10.1016/0196-9781(92)90013-s

Cited by 51 publications

(14 citation statements)

References 30 publications

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“…An important stimulus to NPY synthesis, transport, and release in the hypothalamus may be insulin deficiency. Plasma insulin levels are low in all the above conditions that apparently stimulate hypothalamic NPY, whereas peripheral insulin administration reduces the rise in hypothalamic NPY and NPY mRNA levels in diabetes or fasting (15,23,(29)(30)(31). Insulin crosses the blood-brain barrier and may interact with insulin receptors on neurons in the ARC (28), and insulin may inhibit NPY gene expression directly (30,31).…”

Section: Discussionmentioning

confidence: 94%

“…By contrast, food restriction that normalizes glycemia without correcting insulin deficiency does not reduce hypothalamic NPY levels in diabetic rats (15). Furthermore, peripheral insulin administration increases NPY levels in the ARC of fasted rats (29), and intracerebroventricular injection of insulin reduces NPY mRNA levels in the ARC of fasted rats (30,31). Overall, these findings argue that insulin deficiency is a specific stimulus to NPY synthesis and release in the hypothalamus (27,28,32) and that insulin may act directly to inhibit NPY gene expression (28,30,31).…”

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confidence: 90%

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Effects of Chronic Vanadate Administration in the STZ-Induced Diabetic Rat: The Antihyperglycemic Action of Vanadate Is Attributable Entirely to Its Suppression of Feeding

Dryden

McCarthy

et al. 1994

Diabetes

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Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 90%

Effects of Chronic Vanadate Administration in the STZ-Induced Diabetic Rat: The Antihyperglycemic Action of Vanadate Is Attributable Entirely to Its Suppression of Feeding

Dryden

McCarthy

et al. 1994

Diabetes

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“…We have hypothesized that NPY feeding systems may be rendered refractory in TB rats as a result of ammonia-induced inhibition of adenosine 3', 5'-cyclic monophosphate (42), which is the second messenger for NPY in the neurochemical cascade leading to increased feeding (44). Insulin may also be involved in this feeding mechanism, because recent experiments suggest that peripheral administration of insulin will reduce hypothalamic NPY concentrations (45), perhaps as a result of increased release. Further research is clearly needed, however, to substantiate the many hypotheses associated with this theory of cancer anorexia.…”

Section: Discussionmentioning

confidence: 98%

Insulin reverses ammonia‐induced anorexia and experimental cancer anorexia

Chance

Thomas

Fischer

1994

Nutrition and Cancer

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Previous experiments suggest that experimental cancer-induced anorexia is associated with hyperammonemia and that daily injections of insulin may attenuate the anorexia for several days. In the present study, we determined whether similar daily insulin treatments would correct anorexia induced by the infusion of ammonium salts and compared this feeding response with that of insulin-treated tumor-bearing (TB) rats. Daily treatment of control and anorectic TB rats with systemically administered insulin for six days increased feeding in all control rats and 40% of the TB rats. All insulin-treated groups exhibited equal degrees of hypoglycemia irrespective of anorexia. Basal concentrations of lactate and glucagon were elevated in saline-treated TB rats. Plasma lactate levels were normalized by insulin treatment, whereas glucagon was normalized only in the TB rats that fed to insulin and increased further in TB rats that did not feed to insulin. Elevated hypothalamic tyrosine was reduced in insulin-treated TB rats that ate, and 5-hydroxy-indoleacetic acid was increased further when the rats did not eat. Insulin also blocked anorexia resulting from the intravenous infusion of ammonium salts. Hypothalamic concentrations of tyrosine and tryptophan were increased by the ammonia infusion and reduced significantly in insulin-treated infused rats. These results indicate that insulin treatment can reverse experimental cancer-induced anorexia and hyperammonemia-induced anorexia. Neurochemical changes associated with these treatments are also similar, but not identical.

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“…However, other studies which manipulated plasma insulin also suggest that physiological circulating insulin levels can exert reciprocal effects on hypothalamic NPY activity. Careful systemic insulin treatment lowers hypothalamic NPY and NPY mRNA levels to normal in diabetic rats [81,85] and also attenuates the rise in NPY levels induced in the ARC by food deprivation [144]. Further work has confirmed that the diabetes-induced increases in NPY levels in the ARC and elsewhere are related to insulin deficiency rather than hyperglycaemia; NPY levels did not fall (and indeed rose even higher) when glycaemia was normalized without increasing plasma insulin concentrations, by restricting the diabetic rats' food intake 1871.…”

Section: Insulin and Insulin Deficiencymentioning

confidence: 99%

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Dryden

Frankish

Wang

et al. 1994

Eur J Clin Investigation

123

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Abstract. Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [ 13 (similar estimates probably apply to Western Europe).Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach.This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.

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Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats

Cited by 51 publications

References 30 publications

Effects of Chronic Vanadate Administration in the STZ-Induced Diabetic Rat: The Antihyperglycemic Action of Vanadate Is Attributable Entirely to Its Suppression of Feeding

Effects of Chronic Vanadate Administration in the STZ-Induced Diabetic Rat: The Antihyperglycemic Action of Vanadate Is Attributable Entirely to Its Suppression of Feeding

Insulin reverses ammonia‐induced anorexia and experimental cancer anorexia

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

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