Hyperinsulin Response to Oral Leucine in Obesity and Acromegaly

Johnson, S. R.; Karam, John H.; Levin, Seymour R.; Grodsky, Gerold M.; Forsham, Peter H.

doi:10.1210/jcem-37-3-431

Cited by 16 publications

(4 citation statements)

References 15 publications

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“…In healthy lean individuals oral administration of leucine induces postprandial hyperinsulinemia especially in combination with increased glucose intake [33,34]. In obese subjects, oral administration of leucine induces exaggerated and prolonged postprandial hyperinsulinemia without significant changes of blood glucose levels [34-36]. In children, daily intake of 53 g milk protein, but not of 53 g meat induced hyperinsulinemia and insulin resistance under fasting conditions [10].…”

Section: Introductionmentioning

confidence: 99%

Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

et al. 2013

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Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual’s pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals.

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Section: Introductionmentioning

confidence: 99%

Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

et al. 2013

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“…Infusion of an amino acid mixture to healthy men resulted in elevation of plasma amino acids, hyperinsulinemia and marked activation of S6K1 with increased inhibitory IRS-1 phosphorylation [192] (Figure 2). In comparison to normal subjects, oral doses of leucine (0,2 g/kg) stimulated exaggerated insulin release and induced basal hyperinsulinemia in obese patients [193]. …”

Section: Introductionmentioning

confidence: 99%

The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer

et al. 2012

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Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

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“…5 Characterization of this hyperinsulinism suggests that it consists predominantly of biologically active insulin 6 of normal molecular size 78 whose elevated levels in obese patients represent hypersecretion rather than impaired clearance. 910 This hypersecretion of insulin in obese patients is a consequence of the obesity, since it becomes normal on reducing to normal weight 11 and can be acquired in normal subjects made obese after forced feeding.…”

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confidence: 99%

“Staircase” Glucose Stimulation of Insulin Secretion in Obesity: Measure of Beta-cell Sensitivity and Capacity

et al. 1974

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A special glucose infusion test was used to provide successive steplike increments of glucose stimulation in six normal-weight and seven obese subjects. This "staircase" method of glucose infusion demonstrates that insulin responds in "spike" fashion despite maintenance of a continuous, fixed, submaximal glucose stimulation. Further, the "spike" response recurs as the glucose concentration is stepped up.Obese subjects showed an exaggeration of both the first phase "spike" pattern and the more gradual second phase of insulin release. Mathematical analysis of early phase insulin release indicates that obese persons have greater total amounts of insulin available for release at all glucose concentrations than do normals, yet the proportion of totally available insulin released to a given glucose stimulus is not increased in obesity.These findings imply that the early phase, hyperinsulin response to glucose in obesity is due to a greater quantity of insulin available for release rather than to an increased sensitivity of the beta cell to glucose. DIABETES 23:763-70, September, 1974.In obese patients abnormally high levels of circulating insulin have been found under basal conditions and after pancreatic stimulation with practically all known insulin stimulators, including glucose, 1 tolbutamide, 2 glucagon, 3 arginine, 4 and leucine. 5 Characterization of this hyperinsulinism suggests that it consists predominantly of biologically active insulin 6 of normal molecular size 78 whose elevated levels in obese patients represent hypersecretion rather than impaired clearance. 910 This hypersecretion of insulin in obese patients is a consequence of the obesity, since it becomes normal on reducing to normal weight 11 and can be acquired in normal subjects made obese after forced feeding. 12 The mechanism underlying this hypersecretion of insulin has not yet been determined. It has been attributed to some unknown signal for beta-cell hyperse-

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Hyperinsulin Response to Oral Leucine in Obesity and Acromegaly

Cited by 16 publications

References 15 publications

Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer

“Staircase” Glucose Stimulation of Insulin Secretion in Obesity: Measure of Beta-cell Sensitivity and Capacity

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