Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans

Fruehwald‐Schultes, Bernd; Kern, Werner; Born, Jan; Fehm, H. L.; Peters, Achim

doi:10.1038/sj.ijo.0801695

Cited by 43 publications

(30 citation statements)

References 20 publications

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“…28 (2005) metabolism, may also suppress fat catabolism, and dominance of the fed state may drive insulin secretion, thereby favouring fat deposition. The association of visceral adiposity with hyperinsulinaemia is well recognized, though the exact mechanisms of this relationship are controversial (Bjorntorp 1997;Fruehwald-Schultes 2001;Goran 1997). Furthermore, reduction in skeletal muscle mass may be associated with reduced peripheral insulin sensitivity (Poehlman et al 2000).…”

Section: Discussionmentioning

confidence: 98%

Body composition in young adults with inborn errors of protein metabolism—A pilot study

Wilcox

Strauss

Francis

et al. 2004

J of Inher Metab Disea

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The natural history of inborn errors of protein metabolism and the long-term effects of prescribed semisynthetic therapeutic diets are largely unknown. We assessed body composition, measuring body-fat mass and distribution, fat-free mass, total body protein, total body potassium, bone density and skeletal muscle mass, in young adults (age > 18 years; 6 female, 5 male) with inborn errors of protein metabolism maintained on long-term low-protein diets, compared with controls. Female patients were significantly shorter (159.4 cm vs 169.2 cm, p = 0.013) and had higher BMI (25.3 vs 22.0 kg/m2, p < 0.05), abdominal to gluteal circumference ratio (0.84 vs 0.73, p = 0.011), percentage body fat (42.3% vs 29.5%, p < 0.005) and ratio of central to peripheral body fat (1.15 vs 0.86, p < 0.05) than controls. Male patients had lower height-adjusted total body bone mineral content (0.9 vs 1.02 g/m2, p < 0.04) and skeletal muscle mass (31.1 vs 36.3 kg, p < 0.04) than controls. Compared with controls, patients'nitrogen index was significantly lower (0.91 vs 1.03, p < 0.01), consistent with lower total body protein. Potassium index was significantly higher (121.2% vs 110.4%, p < 0.03), consistent with higher body cell mass, or intracellular water. Documentation of body composition in larger patient series is important to elucidate whether these results reflect increased risks (hence opportunities for prevention) of bone disease, metabolic syndrome and cardiovascular disease in this population.

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Section: Discussionmentioning

confidence: 98%

Body composition in young adults with inborn errors of protein metabolism—A pilot study

Wilcox

Strauss

Francis

et al. 2004

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Likewise, serum cortisol levels were higher during the high-or low-insulin condition. Similarly, during the euglycemic clamp, serum cortisol levels slightly increased in the high-insulin condition, while they decreased in the low-insulin condition [37] . In the previous trial, cortisol concentrations have been increased from baseline during hyperinsulinemic-euglycemic clamp experiments in animals and in humans [39] .…”

Section: Discussionmentioning

confidence: 99%

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Saraç¹,

Saygılı²,

Ozgen³

et al. 2006

Gynecol Obstet Invest

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Background: Idiopathic hirsutism (IH) is the second most common cause of hirsutism, after polycystic ovary syndrome and occurs in about 15% of hirsute women. There are not many studies showing whether patients with IH also have insulin resistance. In the present study, we aimed to investigate the insulin sensivity in IH with non-obese and changing hormone levels during the hyperinsulinemic-euglycemic clamp. Methods: Twenty (20) non-obese women with IH (Group I) ranging in age from 20 to 30 (mean 25 ± 5) years were studied. Hirsutism in women with normal testosterone (T) levels and regular menstrual cycles is as defined IH. Twenty (20) healthy women (mean age 23 ± 2 years) (Group II) were included in this study as the control group. Insulin sensitivity was assessed with modified euglycemic insulin clamp technique. Samples of prolactin, luteinizing hormone (LH), follicle-stimulating hormone, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, cortisol, estradiol, progesterone, 17-OH progesterone (17-OHP), total T, and free T (FT) were obtained at baseline and at 2nd hour during clamp. Results: Steady-state (120 min) glucose disposal rates were higher in Group II than Group I (7.51 ± 0.83 vs. 5.76 ± 1.89 mg/kg/min). Mean FT, ACTH, cortisol, LH, prolactin and 17-OHP levels were found to have decreased statistically significantly (p < 0.05) in Group I. Mean FT, ACTH, and prolactin levels were found to have decreased statistically significantly (p < 0.05) in Group II during the clamp. Mean baseline levels of FT, LH and prolactin were greater in women with hirsutism than in the control subjects (p < 0.05). Insulin mediated glucose disposal was lower in the normal weight women with IH than in those without hirsutism. Conclusions: Mean FT, 17-OHP and dehydroepiandrosterone sulfate levels decreased during euglcemic-hyperinsulinemic clamp in IH.

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“…A hiperinsulinemia poderia ter uma influência estimulatória na atividade do eixo HHA. Evidências têm indicado um efeito estimulatório agudo da insulina durante clamp euglicêmico em homens saudáveis (34). Já foi demonstrado que a insulina atravessa a barreira hematoencefálica (35), e a presença de alta densidade de receptores de insulina na hipófise suporta esta idéia (36).…”

Section: A Síndrome Metabólica E O Sistema Nervoso Simpáticounclassified

Aspectos neuroendócrinos da síndrome metabólica

Matos

Moreira

Guedes

2003

Arq Bras Endocrinol Metab

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Arq Bras Endocrinol Metab vol 47 nº 4 Agosto 2003 410 RESUMOA síndrome metabólica (SM) é caracterizada por alterações no metabolismo glicídico, obesidade, hipertensão e dislipidemia. Estas alterações metabólicas interrelacionam-se com diversos eixos endócrinos controlados pelo hipotálamo e pela hipófise. A obesidade central parece relacionar-se a uma hiperativação do eixo hipotálamo-hipófise-adrenal, como também do sistema nervoso simpático, que poderia levar a um quadro de hipercortisolismo sub-clínico e hipertensão arterial. A SM é também um estado de hipo-somatotropismo relativo relacionado à gordura visceral. Além disso, níveis elevados de ácidos graxos livres e a hiperinsulinemia, secundários à resistência insulínica, estão relacionadas a um bloqueio do eixo somatotrófico. Em homens, a SM relaciona-se a um hipogonadismo tanto por diminuição de gonadotrofinas como por inibição direta da produção de testosterona. Já nas mulheres, existe um excesso de produção de androgênios, principalmente relacionado à hiperinsulinemia, aumento da atividade da aromatase e da liberação de LH. Desta forma, a SM é um estado relacionado a importantes modificações nos mecanismos de feedback responsáveis pelo correto funcionamento dos eixos neuroendócrinos. The metabolic syndrome (MS) is characterized by alterations in carbohydrate metabolism, obesity, hypertension and dislipidemia. These metabolic alterations interfere with some endocrine axes controlled by the hypothalamus and the pituitary. Central obesity might be associated to a state of subclinical hypercortisolism and hypertension, secondary to an activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. MS is also a state of relative hyposomatotropism, probably related to visceral fat. Furthermore, high levels of free fat acids and hyperinsulinemia, secondary to insulin resistance, can contribute to a blockade of the somatotropic axis. In men, MS is related to a state of hypogonadism caused by impairment in gonadotropin secretion and testosterone production. Women exhibit excessive androgen production, secondary to hyperinsulinemia, high levels of LH and to an increase in aromatase activity. In summary, MS is a condition linked to important modifications in feedback mechanisms responsible for the correct functioning of the neuroendocrine axes.

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Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans

Cited by 43 publications

References 20 publications

Body composition in young adults with inborn errors of protein metabolism—A pilot study

Body composition in young adults with inborn errors of protein metabolism—A pilot study

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Aspectos neuroendócrinos da síndrome metabólica

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