Hemorrhage induces the rapid development of hepatic insulin resistance

Ma, Yuchen; Wang, Haichao; Kuebler, Joachim F.; Chaudry, Irshad H.; Messina, Joseph L.

doi:10.1152/ajpgi.00217.2002

Cited by 43 publications

(54 citation statements)

References 57 publications

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“…This increase in fasting glucose is suggestive of insulin resistance and may, in part, be due to a decrease in insulin action in skeletal muscle. In the current studies, the rise in insulin levels varied from animal to animal, resulting in increased insulin levels, but that did not yet reach statistical significance 60 min following hemorrhage ( Figure 2B), as it had by 90 min following hemorrhage (6). Hyperinsulinemia can occur following severe injury.…”

Section: Fasting Serum Glucose Levels Are Increased Following Trauma mentioning

confidence: 56%

“…Protein concentrations were determined (BCA, Pierce, Rockford, IL, USA) and 30 μg/lane of total protein was resolved by SDS-PAGE and transferred to nitrocellulose membranes (6,21,22). The membranes were immunoblotted with anti-phosphoserine-Akt (S473), anti-total Akt, and anti-total ERK1/2 antibodies (Cell Signaling Technology, Beverly, MA, USA); anti-phosphotyrosine-IR (Y972), and anti-phosphotyrosine-IRS-1 (Y612; Invitrogen, Carlsbad, CA, USA); and anti-total IRβ (Santa Cruz Biotechnology, Santa Cruz, CA, USA), also were used.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Hyperinsulinemia can occur following severe injury. However, there appears to be variability depending upon the model used and the time point selected (6,9,25,26). No change or decreases in insulin levels are common early following injury during the "ebb" phase of the injury (27,28).…”

Section: Fasting Serum Glucose Levels Are Increased Following Trauma mentioning

confidence: 99%

“…Thus, traumaalone rats (T0') that were subjected to anesthesia, laparotomy, and catheterization, and then immediately killed were selected as the "baseline" animals in these experiments (6,7). Additional trauma-only groups were subjected to the same procedures and then killed at 30 (T30'), 60 (T60'), and 90 min (T90'), and 5 (T5h) and 24 h (T24h) after catheterization.…”

Section: Experimental Designmentioning

confidence: 99%

“…It is likely that there are multiple possible mechanisms that are disease dependent, and the mechanisms may differ in different insulin target tissues. An acute form of insulin resistance (sometimes called "stress diabetes" or "critical illness diabetes") is observed following severe injuries, surgical trauma, hemorrhage, thermal injury (burn), and sepsis (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). This state of insulin resistance and hyperglycemia can occur rapidly following physical injury, unlike the extended periods often necessary for development of insulin resistance in chronic diseases.…”

Section: Introductionmentioning

confidence: 99%

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Acute, Muscle-Type Specific Insulin Resistance Following Injury

Thompson

Kim

et al. 2008

Mol Med

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Acute insulin resistance can develop following critical illness and severe injury, and the mortality of critically ill patients can be reduced by intensive insulin therapy. Thus, compensating for the insulin resistance in the clinical care setting is important. However, the molecular mechanisms that lead to the development of acute injury/infection-associated insulin resistance are unknown, and the development of acute insulin resistance is much less studied than chronic disease-associated insulin resistance. An animal model of injury and blood loss was utilized to determine whether acute skeletal muscle insulin resistance develops following injury, and surgical trauma in the absence of hemorrhage had little effect on insulin-mediated signaling. However, following hemorrhage, there was an almost complete loss of insulin-induced Akt phosphorylation in triceps, and severely decreased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1. The severity of insulin resistance was similar in triceps and extensor digitorum longus muscles, but was more modest in diaphragm, and there was little change in insulin signaling in cardiac muscle following hemorrhage. Since skeletal muscle is an important insulin target tissue and accounts for much of insulin-induced glucose disposal, it is important to determine its role in injury/infection-induced hyperglycemia. This is the first report of an acute development of skeletal muscle insulin signaling defects. The presented data indicates that the defects in insulin signaling occurred rapidly, were reversible and more severe in some skeletal muscles, and did not occur in cardiac muscle. with insulin resistance, skeletal muscle, adipose tissue, and liver become insulin resistant. However, it is not known which of these three main insulin target tissues become insulin resistant acutely following injury. Since skeletal muscle is a main insulin target tissue, and accounts for approximately 80% of insulin-induced glucose disposal in the human body (19), it is important to understand its role in the acute development of insulin resistance. In the current study, we utilized a rat model of surgical trauma and hemorrhage to determine the development, timing, and muscle selectivity of hemorrhage-induced skeletal muscle insulin resistance. MATERIALS AND METHODS Reagents and MaterialsAll reagents and materials were obtained from Fisher Scientific (Pittsburgh, PA, USA) or Sigma-Aldrich (St. Louis, MO, USA), unless otherwise noted. Animal Model of Surgical Trauma and HemorrhageAll procedures were carried out in accordance with the guidelines set forth in the Guide for the Care and Use of Laboratory Animals and the National Institutes of Health. The experimental protocol was approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham. A model of surgical trauma and hemorrhage in the rat, as previously described (6,7), was used with modifications. Briefly, male SpragueDawley rats received continuous inhalation of low levels of ...

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Section: Fasting Serum Glucose Levels Are Increased Following Trauma mentioning

confidence: 56%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Fasting Serum Glucose Levels Are Increased Following Trauma mentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute, Muscle-Type Specific Insulin Resistance Following Injury

Thompson

Kim

et al. 2008

Mol Med

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Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression

Keeton

et al. 2005

Breast Cancer Res Treat

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The structure of the Gene 33 protein suggests that it plays a role in intracellular signaling and Gene 33 is induced by many mitogenic and stressful stimuli. Previously, we found that Gene 33 expression is significantly induced by retinoic acid (RA), insulin and synergistically by both in a liver-derived cell line. In the present study, we investigated the basal expression and regulation of Gene 33 in multiple human breast cancer cell lines. These cell lines expressed different levels of Gene 33 protein, but Gene 33 protein was not regulated by RA or insulin, either alone, or in combination. However, epidermal growth factor (EGF) induced Gene 33 expression in SK-BR-3 cells and this induction was inhibited by co-treatment with RA. There was a strong correlation between endogenous basal Gene 33 expression and doubling time. Exogenous expression of Gene 33 in MCF-7 cells did not affect cell cycle distribution, but inhibited apoptosis and specifically increased the level of Poly(ADP-ribose) Polymerase (PARP-1) protein. This suggests that Gene 33 promotes breast cancer cell growth by an anti-apoptotic rather than a mitogenic effect, possibly involving up-regulation of PARP-1.

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Insulin regulation of growth hormone receptor gene expression: involvement of both the PI-3 kinase and MEK/ERK signaling pathways

Bennett

Keeton

et al. 2007

Endocr

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The mechanism(s) of insulin's effects on growth hormone receptor (GHR) gene expression are poorly understood. Using rat hepatoma cells, we have previously shown that insulin treatment reduces GHR mRNA and protein in a time- and concentration-dependent manner, at least in part via down-regulation of GHR transcription. The present study determines whether the phosphatidylinositol-3 kinase (PI-3 kinase) and mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways are involved in mediating these effects of insulin. Inhibition of the PI-3 kinase pathway partially blocked insulin's reduction of GHR mRNA, as did inhibition of the MEK/ERK pathway, resulting in higher GHR mRNA levels. Inhibition of both pathways was necessary to completely block insulin effects. Similar results were obtained for GHR protein. Collectively, these data suggest that insulin signaling via either the PI-3 kinase or MEK/ERK pathway may result in partial reduction of GHR gene expression, whereas signaling via both pathways may be required to achieve the full insulin effect.

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Hemorrhage induces the rapid development of hepatic insulin resistance

Cited by 43 publications

References 57 publications

Acute, Muscle-Type Specific Insulin Resistance Following Injury

Acute, Muscle-Type Specific Insulin Resistance Following Injury

Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression

Insulin regulation of growth hormone receptor gene expression: involvement of both the PI-3 kinase and MEK/ERK signaling pathways

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