Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone

Nyberg, Gudrun; Boström, S.; Smith, Ulf

doi:10.1530/acta.0.0950129

Cited by 19 publications

(10 citation statements)

References 15 publications

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“…A long-term elevation of the circulating levels ofgrowth hormone may induce a state of insulin resistance (32,33). Furthermore, long-term exposure of human adipocytes to growth hormone in vitro markedly reduced the basal and insulinstimulated rates ofglucose metabolism (34,35). However, there is probably no direct effect of the circulating growth hormone level on insulin action on adipose tissue in acromegaly, since we observed similar insulin effects in acromegaly patients with high and low growth hormone levels.…”

Section: Discussionmentioning

confidence: 62%

Insulin action in human adipose tissue in acromegaly.

Bolinder¹,

Östman²,

Werner³

et al. 1986

J. Clin. Invest.

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The mechanisms underlying insulin resistance in acromegaly were investigated. Adipose tissue was obtained from nine patients with acromegaly who had in vivo insulin resistance and from 14 matched healthy control subjects. Receptor binding and the antilipolytic effect of insulin were determined in isolated fat cells. Insulin-induced glucose oxidation at a physiological hexose concentration was investigated in fat segments. In fat cells obtained from acromegaly patients after an overnight fast, insulin binding at low hormone concentrations was significantly reduced by 20-30%, insulin-induced antilipolysis was unchanged, but glucose oxidation was unresponsive to insulin. Since it has recently been observed that glucose feeding may rapidly modify insulin action in human adipocytes, fat cells were also obtained 60 min after an 100-g oral glucose load. In this situation, insulin binding at low hormone concentrations was further reduced to one-half of that in the control group, and the sensitivity of insulin-induced antilipolysis was markedly decreased in acromegaly. It is concluded that, in the fasting state, the action of insulin on glucose utilization but not on lipolysis is impaired in adipose tissue of acromegalic patients because of a postreceptor defect. After glucose ingestion, the resistance to insulin in acromegaly is further enhanced and antilipolysis is also impaired. Altered coupling between receptor and effector alone or in combination with an additional decrease in receptor binding may explain the enhancement of insulin resistance. These mechanisms may be essential factors in the pathogenesis of insulin resistance in acromegaly.

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Section: Discussionmentioning

confidence: 62%

Insulin action in human adipose tissue in acromegaly.

Bolinder¹,

Östman²,

Werner³

et al. 1986

J. Clin. Invest.

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“…Human adipocytes, like rat adipocytes, are target cells for GH [2-71. However, only the insulinantagonistic effect of hGH has been demonstrated in human fat cells [5] while rat fat cells respond with both an initial insulin-like and a subsequent insulin-antagonistic effect [6,7].…”

Section: Discussion Hgh (= 100%)mentioning

confidence: 99%

Specific binding of human growth hormone but not insulin‐like growth factors by human adipocytes

et al. 1986

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Binding of human GH (hGH) and insulin-like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24°C was reached at 120 min and half-maximal specific binding at 6-8 ng/ml. Apparent K, was 2.1 x log M-l and B,,, 7.3 x 10 -ii M/lo6 cells. The human fat cell growth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated.Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species. Growth hormone InsulinInsulin-like growth factor Adipocyte

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“…in 5). Studies showing direct actions of GH in adipose cells or tissue include: kinetic studies in pigs, which demonstrated that GH-induced insulin resistance results predominantly from reduced incorporation of glucose into adipose tissue (6,7); studies in 3T3-L1 and 3T3-F442A adipocytes showing that GH inhibits insulin action on glucose transport and lipid accumulation (5,8); and studies in human adipose tissue and adipocytes showing that GH reduces the incorporation of glucose into triglycerides (9). It has been proposed that GH-induced insulin resistance in adipocytes is caused by a mechanism involving the phosphoinositide (PI) 3-kinase signaling pathway (10).…”

mentioning

confidence: 99%

Growth Hormone Regulation of p85α Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue

et al. 2007

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Phosphoinositide (PI) 3-kinase is involved in insulin-mediated effects on glucose uptake, lipid deposition, and adiponectin secretion from adipocytes. Genetic disruption of the p85␣ regulatory subunit of PI 3-kinase increases insulin sensitivity, whereas elevated p85␣ levels are associated with insulin resistance through PI 3-kinase-dependent and -independent mechanisms. Adipose tissue plays a critical role in the antagonistic effects of growth hormone (GH) on insulin actions on carbohydrate and lipid metabolism through changes in gene transcription. The objective of this study was to assess the role of the p85␣ subunit of PI 3-kinase and PI 3-kinase signaling in GH-mediated insulin resistance in adipose tissue. To do this, p85␣ mRNA and protein expression and insulin receptor substrate (IRS)-1-associated PI 3-kinase activity were measured in white adipose tissue (WAT) of mice with GH excess, deficiency, and sufficiency. Additional studies using 3T3-F442A cells were conducted to confirm direct effects of GH on free p85␣ protein abundance. We found that p85␣ expression 1) is decreased in WAT from mice with isolated GH deficiency, 2) is increased in WAT from mice with chronic GH excess, 3) is acutely upregulated in WAT from GH-deficient and -sufficient mice after GH administration, and 4) is directly upregulated by GH in 3T3-F442A adipocytes. The insulininduced increase in PI 3-kinase activity was robust in mice with GH deficiency, but not in mice with GH excess. In conclusion, GH regulates p85␣ expression and PI 3-kinase activity in WAT and provides a potential explanation for 1) the insulin hypersensitivity and associated obesity and hyperadiponectinemia of GH-deficient mice and 2) the insulin resistance and associated reduced fat mass and hypoadiponectinemia of mice with GH excess. Diabetes

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Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone

Cited by 19 publications

References 15 publications

Insulin action in human adipose tissue in acromegaly.

Insulin action in human adipose tissue in acromegaly.

Specific binding of human growth hormone but not insulin‐like growth factors by human adipocytes

Growth Hormone Regulation of p85α Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue

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