Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.

Boden, Guenther; Chen, Xinhua; Kolaczynski, Jerzy W.; Polansky, Marcia

doi:10.1172/jci119621

Cited by 264 publications

(169 citation statements)

References 36 publications

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“…This general pattern has been confirmed in adolescent girls [69], young men [33] and lean [70] and obese [71] adults. Some reports describe earlier nadirs at 0900 hours [72,73], although the overall pattern is similar (Fig.…”

Section: Leptin Diurnal Rhythm and Pulsatilitymentioning

confidence: 53%

“…These data suggest that the effect of insulin on serum leptin concentrations depends on the patient's previous nutritional state. Hyperinsulinaemia (about 900 pmol/l) increased serum leptin concentrations after 8 h in a dose-dependent manner in lean men but hyperglycaemia or high-plasma fatty acid concentrations did not affect leptin [33].…”

Section: Regulation Of Leptin By Insulinmentioning

confidence: 83%

“…Although serum betahydroxybutyrate increases fivefold over baseline during 60 h of fasting and is inversely correlated with serum leptin concentrations, there was no association between serum leptin and glucose, insulin or fatty acid concentrations [31]. Further, plasma free fatty acid concentrations themselves do not appear to regulate leptin concentration [32,33].…”

Section: Leptin Regulation By Fasting Refeeding and Overfeedingmentioning

confidence: 92%

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Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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OverviewPositional cloning of the defective gene in genetically obese ob/ob mice identified leptin as the long-sought hormone that communicates information about adipocyte metabolism to the brain [1]. Supplying leptin to genetically deficient ob/ob mice increases metabolic rate, body temperature and general activity and decreases food intake, body weight and adiposity [1±4]. Additionally, the importance of leptin to reproduction has been highlighted by the lack of sexual maturation in people who are genetically deficient in leptin [5] or the leptin receptor [6]. Although many of leptin's effects are centrally mediated, there is growing evidence that peripheral leptin receptors mediate leptin's proliferative effects on haemopoietic cells [7] and its anti-lipogenic effects on muscle and pancreatic islets [8,9].Because leptin has a critical role in regulating energy metabolism, adipose stores and body weight, questions have been raised concerning the control of leptin synthesis and secretion and the function of leptin in controlling satiety and food intake. Basal or fasting leptin values are higher in women than men, increase during the course of pregnancy and, in both healthy adults and those with Type II (non-insulindependent) diabetes mellitus, are strongly correlated with per cent body fat or BMI [10,11] and adipose tissue mass [12±15]. Despite these strong correlations, people with similar degrees of adiposity have circulating leptin concentrations that vary considerably. Thus, factors other than adipocyte size and fat content must influence leptin production. Further, the regulation of leptin's diurnal pattern of secretion is still to be explained.In this review we summarize current data, primarily from human studies, that address the nutritional controls on leptin synthesis and secretion and point out fruitful areas for future study. Excellent recent reviews should be consulted for information on the leptin receptor, other aspects of leptin's effects, and the relation of leptin to other hormones that regulate food intake and energy expenditure [16±22]. Leptin regulation by fasting, refeeding and overfeedingFasting and refeeding. During short-term energy restriction, plasma leptin concentrations decrease much more than the amount of weight or adipose tissue lost. For example, lean and obese adults who fasted for 52 to 96 h lost less than 4 % of body weight but the leptin concentrations decreased 54 to 72 % [23±25]. In careful long-term studies of lean and obese people who were either losing weight or maintaining a defined weight loss, leptin concentrations were lower during the period of loss than the period of weight maintenance at the same body composition [26]. After a 4 day fast followed by an additional 6 days of fasting during which an intravenous infusion of 5 % glucose was given, leptin increased 80 % within the first 24 h, even though glucose provided only 338 kcal/day [25]. Although it is possible that the previous 4 day fast confounded these results [27], taken together, these studies suggest that ...

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Section: Leptin Diurnal Rhythm and Pulsatilitymentioning

confidence: 53%

Section: Regulation Of Leptin By Insulinmentioning

confidence: 83%

Section: Leptin Regulation By Fasting Refeeding and Overfeedingmentioning

confidence: 92%

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Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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“…The present results, together with these data, indicate that circulating leptin is susceptible to decline, presumably dependent on the decrease in serum insulin. In contrast, the prevailing observations from human studies suggest that leptin secretion is rather robust against the acute stimulation by insulin, as mentioned in the introduction [2, [7][8][9]. These characteristics of the relationship between insulin and leptin in humans seem favorable to gain and maintain body fat, together with the well-described "leptin resistance" in obesity.…”

Section: Discussionmentioning

confidence: 99%

“…This postprandial increase might be attributed to the direct action of insulin, and is thought to participate in regulating food intake and energy expenditure in rodents [1]. In contrast, leptin mRNA expression can be enhanced in human adipocytes only after incubation with insulin for longer than 72 hrs [2,7], and prolonged and supraphysiological insulinemia is necessary to significantly increase serum leptin in healthy subjects [2] and in type 1 diabetic patients with ketoacidosis or ketosis [8,9]. These results suggest that leptin secretion is robust against stimu-lation by insulin in humans.…”

mentioning

confidence: 99%

Crucial Role of Insulin in Leptin Maintenance. Profound Decrease in Serum Leptin by Octreotide Acetate in Insulinoma Subjects.

Nakamura¹,

Nagasaka²,

Ishikawa³

et al. 2000

Endocr J

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Abstract. To further clarify the relationship between insulin and leptin, time course changes in plasma glucose, serum insulin and leptin levels were analyzed after subcutaneous administration of 100 pg octreotide acetate in two insulinoma subjects. Octreotide acetate induced a prompt decrease in serum insulin level, accompanied with an increase in plasma glucose in both patients. Following the decrease in serum insulin level, serum leptin concentrations were profoundly decreased by 66% and 44%, 8-12 hrs after octreotide injection; that is, the concentrations decreased from 41.1 to 13.8 ng/ml in patient 1, and from 17.5 to 9.8 ng/ml in patient 2. Daily profiles of plasma glucose, serum insulin and leptin without octreotide administration did not show such alterations in these indexes in patient 1. These data show that circulating leptin may be susceptible to decline dependent on the decrease in serum insulin, suggesting that insulin plays a crucial role in the maintenance of leptin secretion in humans.

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Leptin: A Metabolic Perspective

Penn

Rooks

Harris

2007

Handbook of Contemporary Neuropharmacology

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The history of discovery of leptin is given and current knowledge on the factors that regulate ob gene expression and leptin protein secretion is summarized. The chapter focuses on the metabolic effects of leptin, the pathways involved in the suppression of food intake and stimulation of energy expenditure are described. The role of central activation of sympathetic outflow to peripheral tissues, compared with direct effects of leptin on insulin‐sensitive tissues, in mediating metabolic responses to leptin is discussed. Recent work elucidating the cellular basis for the shift in metabolism of adipose and non‐adipose tissue to lipid oxidation and triglyceride depletion is reviewed.

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Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.

Cited by 264 publications

References 36 publications

Nutritional regulation of leptin in humans

Nutritional regulation of leptin in humans

Crucial Role of Insulin in Leptin Maintenance. Profound Decrease in Serum Leptin by Octreotide Acetate in Insulinoma Subjects.

Leptin: A Metabolic Perspective

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