The evaluation of insulin as a metabolic signal influencing behavior via the brain

Woods, Stephen C.; Chavez, Mark; Park, Collin R.; Riedy, Christine A.; Kaiyala, Karl J.; Richardson, Ralph D.; Figlewicz, Dianne P.; Schwartz, Michael W.; Porte, Daniel; Seeley, Randy J.

doi:10.1016/0149-7634(95)00044-f

Cited by 120 publications

(61 citation statements)

References 30 publications

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“…At the behavioral level, insulin/IR has been implicated in at least two major brain functions: feeding behavior (3,24) and cognition, including learning and memory (25). A role for insulin/IR in learning and memory is supported by several findings.…”

supporting

confidence: 48%

Brain Insulin Receptors and Spatial Memory

Zhao

Hui

et al. 1999

Journal of Biological Chemistry

481

154

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supporting

confidence: 48%

Brain Insulin Receptors and Spatial Memory

Zhao

Hui

et al. 1999

Journal of Biological Chemistry

481

154

View full text Add to dashboard Cite

“…These effects of leptin are thought to be largely mediated by hypothalamic neuropeptide systems regulating energy balance (Woods et al 1998;Schwartz et al 1999). Thus, leptin, along with insulin which also has direct actions in the CNS to regulate food intake and energy expenditure (Schwartz et al 1994;Woods et al 1996), functions as a negative feedback signal to the CNS to regulate energy balance (Fig. 1).…”

Section: Discovery Of Leptin and Effects On Food Intakementioning

confidence: 99%

Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

2000

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Adipose tissue performs complex metabolic and endocrine functions. Among the endocrine products produced by adipose tissue are tumour necrosis factor α, interleukin 6, acylationstimulating protein and leptin. The present review will focus primarily on mechanisms regulating leptin production and leptin action, and the implications of this regulation in the control of energy balance. Leptin acts in the central nervous system where it interacts with a number of hypothalamic neuropeptide systems to regulate feeding behaviour and energy expenditure. The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance. Insulin is the major regulator of leptin production by adipose tissue. Insulin infusions increase circulating leptin concentrations in human subjects. Plasma leptin levels are markedly decreased in insulin-deficient diabetic rodents, and the low leptin levels contribute to diabetic hyperphagia. Based on in vitro studies, the effect of insulin to stimulate leptin production appears to involve increased glucose metabolism. Blockade of glucose transport or glycolysis inhibits leptin expression and secretion in isolated adipocytes. Evidence suggests that anaerobic metabolism of glucose to lactate does not stimulate leptin production. Alterations in insulin-mediated glucose metabolism in adipose tissue are likely to mediate the effects of energy restriction to decrease, and refeeding to increase, circulating leptin levels. Changes in glucose metabolism may also explain the observation that high-fat meals lower 24 h circulating leptin levels relative to high-carbohydrate meals in human subjects, suggesting a mechanism that may contribute to the effects that high-fat diets have in promoting increased energy intake, weight gain and obesity. The decreased circulating leptin observed during energy restriction is related to increased sensations of hunger in human subjects. Thus, decreases in leptin during energyrestricted weight-loss regimens may contribute to the strong propensity for weight regain. A better understanding of the precise mechanisms regulating leptin production and leptin action may lead to new approaches for managing obesity.

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“…The hypothesis of the first experiment was that increasing levels of hyperinsulinemia would lead a decrease in mesoaccumbens DA. This rationale emerged from the extensive series of studies that have shown that chronic (i.e., several days) or acute [17] third ventricle insulin administration reduces daily food intake and results in a decrease in body weight via insulin's action on the arcuate nucleus of the hypothalamus [18][19][20][21]. Based on this research and since hyperdopaminergic conditions have been reported to stimulate food intake [22,23], a similar catabolic role, that is a decrease in DA should be observed in the mesoaccumbens DA system in response to short-term elevations in plasma insulin levels.…”

Section: Introductionmentioning

confidence: 99%

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Bello

Hajnal

2006

Physiology & Behavior

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Dopaminergic systems have been implicated in diabetes and obesity. Notwithstanding, the most basic relationship between dopamine and plasma insulin as well as glucose levels yet remains unknown. The present experiments were designed to investigate the effects of acute hyperinsulinemia on basal dopamine levels in the nucleus accumbens of the rat under chloral hydrate anesthesia using acute microdialysis in combination with the hyperinsulinemic-glycemic clamping procedure. In Experiment 1, each rat was infused with one of three concentrations of insulin (2.4, 4.8, or 9.6 mU/ kg per min) while plasma glucose levels were maintained at euglycemia (∼5.5 mmol/L). Dopamine, dihydroxyphenylacetic acid and homovanillic acid were not significantly different from baseline during either the clamp or post clamp periods for all insulin concentrations. In Experiment 2, rats were infused with the highest concentration of insulin (9.6 mU/kg per min) and plasma glucose levels were maintained at either hypoglycemia (∼3 mmol/L) or hyperglycemia (∼14 mmol/L). Dopamine was elevated at 100 min (+113% above basal levels) and 120 min (+117%) in the hypoglycemic condition and at 120 min (+121%) in the hyperglycemic condition. In the hyperglycemic post clamp period, homovanillic acid was decreased below basal levels (approximately -32%). These results together suggest that short-term blood glucose deviations coupled with acute hyperinsulinemia affect the mesoaccumbens dopamine system.

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The evaluation of insulin as a metabolic signal influencing behavior via the brain

Cited by 120 publications

References 30 publications

Brain Insulin Receptors and Spatial Memory

Brain Insulin Receptors and Spatial Memory

Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

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