Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.

Rajkumar, K.; Kršek, Michal; Dheen, S. Thameem; Murphy, LJ

doi:10.1172/jci118982

Cited by 87 publications

(101 citation statements)

References 34 publications

(43 reference statements)

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“…Burn-induced changes in the mRNA expressions of IGF-I and its binding proteins, especially IGFBP-1 and IGFBP-3, have already been shown also to result in similar changes in plasma content of their proteins (41,42). Therefore, increased mRNA expression of IGFBP-1 in liver and muscle may further dampen the activity of already reduced levels of IGF-I through inhibiting its functions (15,56,57). It has been suggested that the increase in skeletal muscle IGFBP-3 mRNA expression, and hence IGFBP-3, may also inhibit IGF-I actions (41,56).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

Balasubramaniam

Joshi²,

Su³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Balasubramaniam A, Joshi R, Su C, Friend LA, Sheriff S, Kagan RJ, James JH. Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx. Am J Physiol Regul Integr Comp Physiol 296: R893-R901, 2009. First published February 11, 2009; doi:10.1152/ajpregu.00015.2008.-We previously determined that ghrelin synthesis was downregulated after burn injury and that exogenous ghrelin retained its ability both to stimulate food intake and to restore plasma growth hormone levels in burned rats. These observations and the finding that anabolic hormones can attenuate skeletal muscle catabolism led us to investigate whether ghrelin could attenuate burn-induced skeletal muscle protein breakdown in rats. These studies were performed in young rats (50 -60 g) 24 h after ϳ30% total body surface area burn injury. Burn injury increased total and myofibrillar protein breakdown in extensor digitorum longus (EDL) muscles assessed by in vitro tyrosine and 3-methyl-histidine release, respectively. Continuous 24-h administration of ghrelin (0.2 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 ) significantly inhibited both total and myofibrillar protein breakdown in burned rats. Ghrelin significantly attenuated burninduced changes in mRNA expression of IGFBP-1 and IGFBP-3 in liver. In EDL, ghrelin attenuated the increases in mRNA expression of the binding proteins, but had no significant effect on reduced expression of IGF-I. Ghrelin markedly reduced the elevated mRNA expression of TNF-␣ and IL-6 in EDL muscle that occurred after burn. Moreover, ghrelin normalized plasma glucocorticoid levels, which were elevated after burn. Expression of the muscle-specific ubiquitinligating enzyme (E3) ubiquitin ligases MuRF1 and MAFbx were markedly elevated in both EDL and gastrocnemius and were normalized by ghrelin. These results suggest that ghrelin is a powerful anticatabolic compound that reduces skeletal muscle protein breakdown through attenuating multiple burn-induced abnormalities.

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Section: Discussionmentioning

confidence: 99%

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

Balasubramaniam

Joshi²,

Su³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Error bars represent SE; *P Ͻ 0.05 for unpaired t-test. indicative of mild insulin resistance (36). This genetic mutation also causes glucose intolerance later in life (13).…”

Section: Discussionmentioning

confidence: 99%

Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I

Salmon

Lerner

Ikeno

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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The extension of lifespan due to reduced insulin-like growth factor 1 (IGF-I) signaling in mice has been proposed to be mediated through alterations in metabolism. Previously, we showed that mice homozygous for an insertion in the Igf1 allele have reduced levels of IGF-I, are smaller, and have an extension of maximum lifespan. Here, we tested whether this specific reduction of IGF-I alters glucose metabolism both on normal rodent chow and in response to high-fat feeding. We found that female IGF-I-deficient mice were lean on a standard rodent diet but paradoxically displayed an insulin-resistant phenotype. However, these mice gained significantly less weight than normal controls when placed on a high-fat diet. In control animals, insulin response was significantly impaired by high-fat feeding, whereas IGF-I-deficient mice showed a much smaller shift in insulin response after high-fat feeding. Gluconeogenesis was also elevated in the IGF-I-deficient mice relative to controls on both normal and high-fat diet. An analysis of metabolism and respiratory quotient over 24 h indicated that the IGF-I-deficient mice preferentially utilized fatty acids as an energy source when placed on a high-fat diet. These results indicate that reduction in the circulating and tissue IGF-I levels can produce a metabolic phenotype in female mice that increases peripheral insulin resistance but renders animals resistant to the deleterious effects of high-fat feeding.

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“…Distinguishing between these possibilities in vivo will require additional studies involving the systemic administration of non-IGF-binding mutants of IGFBP-3. Hyperglycemia has been convincingly demonstrated after the injection of IGFBP-1 (21) in rats and in transgenic mice, which overexpress IGFBP-1 (22), however, an IGF-dependent mechanism for this phenomena has been postulated.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein-3 Induces Insulin Resistance in Adipocytes In Vitro and in Rats In Vivo

et al. 2007

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Insulin-like growth factor binding protein (IGFBP)-3 binds to IGF and modulates their actions and also possesses intrinsic activities. We investigated its effects on insulin action and found that when IGFBP-3 was added to fully differentiated 3T3-L1 adipocytes in culture, insulin-stimulated glucose transport was significantly inhibited to 60% of control in a time-and dose-dependent manner. Tumor necrosis factor (TNF)-␣ treatment also inhibited glucose transport to the same degree as IGFBP-3 and, in addition, increased IGFBP-3 levels 3-fold. Co-treatment with TNF-␣ and IGFBP-3 antisense partially prevented the inhibitory effect of TNF-␣ on glucose transport, indicating a role for IGFBP-3 in cytokine-induced insulin resistance. Insulin-stimulated phosphorylation of the insulin receptor was markedly decreased by IGFBP-3 treatment. IGFBP-3 treatment suppressed adiponectin expression in 3T3-L1 adipocytes. Infusion of IGFBP-3 to Sprague-Dawley rats for 3 h decreased peripheral glucose uptake by 15% compared with controls as well as inhibiting glycogen synthesis. Systemic administration of IGFBP-3 to rats for 7 d resulted in a dramatic 40% decrease in peripheral glucose utilization and glycogen synthesis. These in vitro and in vivo findings demonstrate that IGFBP-3 has potent insulin-antagonizing capability and suggest a role for IGFBP-3 in cytokine-induced insulin resistance and other mechanisms involved in the development of type-2 diabetes. (Pediatr Res 61: 159-164, 2007)

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Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.

Cited by 87 publications

References 34 publications

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I

Insulin-Like Growth Factor Binding Protein-3 Induces Insulin Resistance in Adipocytes In Vitro and in Rats In Vivo

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