Detrimental effect of hyperosmolality on insulin-stimulated glucose metabolism in adipose and muscle tissue in vitro

Komjati, M.; Kastner, Gerhard; Waldhäusl, W.; Bratusch-Marrain, P.

doi:10.1016/0885-4505(88)90091-6

Cited by 25 publications

(17 citation statements)

References 16 publications

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“…Thus insulin-induced glucose uptake by rat epididymal fat pads is markedly reduced under hyperosmotic conditions [28]. This was recently supported using 3T3-L1 adipocytes: insulinstimulated glucose uptake and GLUT4 translocation were completely abolished in presence of hyperosmolarity [29].…”

Section: Cell Hydration and Insulin Resistancementioning

confidence: 67%

Cell Hydration and Insulin Signalling

Schliess

Häussinger²

2000

Cell Physiol Biochem

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Changes in cell hydration are critically important for the signalling towards metabolic responses to hormones, substrates and reactive oxygen intermediates. In liver insulin-induced cell swelling is due to a net K⁺-uptake resulting from the concerted activation of Na⁺/K⁺/2Cl^- cotransport, Na⁺/H⁺ exchange and the Na⁺/K⁺-ATPase. Insulin-induced swelling is essential for generating the antiproteolytic response to the hormone, which depends on activation of the MAP-kinase p38. Recent investigations show, that cell swelling induced by either hypoosmolarity or insulin triggers the activation of signalling cascades. Cell swelling by insulin is Ptdins-3-kinase mediated and contributes to the activation of Erk- and p38-type MAP-kinases. Conditions dehydrating insulin target tissues such as hyperosmolarity or amino acid deprivation are frequently associated with insulin resistance. In liver, hyperosmolarity impairs the Ptdins-3-kinase-dependent K⁺ uptake and cell swelling in response to insulin, leading to resistance of MAP-kinases and proteolysis to regulation by insulin. Likewise, a reduction of insulin-induced swelling by the loop diuretics furosemide and bumetanide cause insulin resistance shown by the levels of cell swelling, MAP-kinase activation and proteolysis control. Blockage of the cell volume response to insulin may be the common denominator in dehydration-induced insulin resistance found in clinical settings such as sepsis, burn injury and diabetes mellitus.

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Section: Cell Hydration and Insulin Resistancementioning

confidence: 67%

Cell Hydration and Insulin Signalling

Schliess

Häussinger²

2000

Cell Physiol Biochem

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“…Th ese changes were also seen with only mild deviations of serum sodium from the normal range. By contrast, complications of hypernatraemia and consequent hyperosmolality are manifold, and include decrease in cardiac contractility, decreased glucose utilization, insulin resistance, cognitive impairment and cerebral shrinkage leading to vascular rupture [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Dysnatraemias in the emergency room: Undetected, untreated, unknown?

Arampatzis

Exadaktylos

Buhl

et al. 2011

Wien Klin Wochenschr

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Dysnatraemias are present in almost 1 in 5 patients who presented to the emergency department. Contrarily to patients who are already hospitalized, hypernatraemia was by far more common than hyponatraemia in patients at the emergency department. Surprisingly, patients with hyponatraemia were significantly older than normonatraemic patients while there was no age difference in hypernatraemic patients. Dysnatraemias are common in the emergency room and further studies are indicated to evaluate the causes and the impact on outcome of patients.

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“…However, like several other insulinomimetic agents, hyperosmolarity not only partly activates several insulin-specific biological responses but also induces a state of insulin resistance. Indeed, in rat epididymal fat cells, hyperosmotic stress markedly reduces insulin-induced glucose transport (11). In perfused rat liver, hyperosmolarity impairs insulin-mediated cell swelling and reverses the proteolysis inhibition induced by insulin (12).…”

mentioning

confidence: 97%

Hyperosmotic Stress Inhibits Insulin Receptor Substrate-1 Function by Distinct Mechanisms in 3T3-L1 Adipocytes

Gual¹,

González

Grémeaux

et al. 2003

Journal of Biological Chemistry

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In 3T3-L1 adipocytes, hyperosmotic stress was found to inhibit insulin signaling, leading to an insulin-resistant state. We show here that, despite normal activation of insulin receptor, hyperosmotic stress inhibits both tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphoinositide 3 (PI 3)-kinase activity in response to physiological insulin concentrations. Insulin-induced membrane ruffling, which is dependent on PI 3-kinase activation, was also markedly reduced. These inhibitory effects were associated with an increase in IRS-1 Ser 307 phosphorylation. Furthermore, the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented the osmotic shock-induced phosphorylation of IRS-1 on Ser 307 . The inhibition of mTOR completely reversed the inhibitory effect of hyperosmotic stress on insulin-induced IRS-1 tyrosine phosphorylation and PI 3-kinase activation. In addition, prolonged osmotic stress enhanced the degradation of IRS proteins through a rapamycin-insensitive pathway and a proteasome-independent process. These data support evidence of new mechanisms involved in osmotic stress-induced cellular insulin resistance. Short-term osmotic stress induces the phosphorylation of IRS-1 on Ser 307 by an mTOR-dependent pathway. This, in turn, leads to a decrease in early proximal signaling events induced by physiological insulin concentrations. On the other hand, prolonged osmotic stress alters IRS-1 function by inducing its degradation, which could contribute to the down-regulation of insulin action.Insulin regulates blood glucose levels through multiple regulatory mechanisms such as suppression of endogenous glucose production in liver and stimulation of glucose uptake into muscle and adipocytes (1). Glucose transport in muscle and adipose tissues is caused by the translocation of the glucose transporter Glut 4 from an intracellular pool to the plasma membrane. These biological responses require tyrosine phosphorylation of IRS-1, 1 which, in turn, binds and activates PI 3-kinase. Downstream effectors of PI 3-kinase such as protein kinase B (PKB) or atypical PKC could be involved in Glut 4 translocation (2, 3). Further, it has been recently shown that insulin-induced Glut 4 translocation also requires the activation of the adaptor protein containing PH and SH2 domain (APS)/Cbl-associated protein (CAP)/Cbl/Crk-II/TC10 pathway independent of PI 3-kinase activation (4 -6). Other stimuli, such as osmotic shock, can promote Glut 4 translocation. However, osmotic shock only partly mimics the insulin effect on Glut 4 translocation and glucose uptake. The effect induced by osmotic stress requires the tyrosine phosphorylation of the adaptor protein Grb2-Associated binder-1 and is independent of PI 3-kinase/PKB activation (7-10). We have recently shown that both osmotic shock and insulin share the Crk-II/TC10 pathway to stimulate Glut 4 translocation (10). However, like several other insulinomimetic agents, hyperosmolarity not only partly activates several insulin-specific biologica...

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Detrimental effect of hyperosmolality on insulin-stimulated glucose metabolism in adipose and muscle tissue in vitro

Cited by 25 publications

References 16 publications

Cell Hydration and Insulin Signalling

Cell Hydration and Insulin Signalling

Dysnatraemias in the emergency room: Undetected, untreated, unknown?

Hyperosmotic Stress Inhibits Insulin Receptor Substrate-1 Function by Distinct Mechanisms in 3T3-L1 Adipocytes

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