Infusion of β-Endorphin Improves Insulin Resistance in Fructose-fed Rats

Su, Chin-Hui; Chang, Y.-Y.; Pai, Hui-Ching; Liu, I.-M.; Lo, Chia-Ying; Cheng, Juei‐Tang

doi:10.1055/s-2004-825763

Cited by 33 publications

(31 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Sham-burned rats were immersed in lukewarm water. Analgesics affect not only insulin sensitivity (9,35,49) but also Akt/PKB and ERK activities (35). The responsiveness to opioids is also altered by burn injury (27,38).…”

Section: Methodsmentioning

confidence: 99%

Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle

Sugita

Kaneki²,

Sugita³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

The molecular bases underlying burn-or critical illness-induced insulin resistance still remain unclarified. Muscle protein catabolism is a ubiquitous feature of critical illness. Akt/PKB plays a central role in the metabolic actions of insulin and is a pivotal regulator of hypertrophy and atrophy of skeletal muscle. We therefore examined the effects of burn injury on insulin-stimulated Akt/PKB activation in skeletal muscle. Insulin-stimulated phosphorylation of Akt/PKB was significantly attenuated in burned compared with sham-burned rats. Insulin-stimulated Akt/PKB kinase activity, as judged by immune complex kinase assay and phosphorylation status of the endogenous substrate of Akt/PKB, glycogen synthase kinase-3␤ (GSK-3␤), was significantly impaired in burned rats. Furthermore, insulin consistently failed to increase the phosphorylation of p70 S6 kinase, another downstream effector of Akt/PKB, in rats with burn injury, whereas phosphorylation of p70 S6 kinase was increased by insulin in controls. The protein expression of Akt/PKB, GSK-3␤, and p70 S6 kinase was unaltered by burn injury. However, insulin-stimulated activation of ERK, a signaling pathway parallel to Akt/PKB, was not affected by burn injury. These results demonstrate that burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle and suggest that attenuated Akt/PKB activation may be involved in deranged metabolism and muscle wasting observed after burn injury.protein kinase B; glycogen synthase kinase-3␤; insulin resistance FUNCTIONAL AND METABOLIC ABERRATIONS associated with critical illness such as burn injury include hypermetabolic response, increased protein catabolism, insulin resistance, and muscle wasting. Muscle wasting in critically ill patients leads to muscle weakness, resulting in hypoventilation, difficulties in weaning off respirators, decreased mobilization, prolonged rehabilitation and hospitalization, and even death (2, 3, 4, 6). Insulin resistance is a well-known phenomenon of critical illness and has long been considered to play a cardinal role in the derangements of metabolism and muscle wasting. Binding of insulin to its receptor results in activation of insulin receptor (IR) tyrosine kinase, which in turn phosphorylates the IR substrates (IRSs). Phosphorylation at the tyrosine residues of IRS-1 and IRS-2 transduces signal from IR to phosphatidylinositol 3-kinase (PI3K) (1, 4).A Ser/Thr protein kinase, Akt/PKB, is a major downstream effector of the IR-IRS-PI3K pathway. Akt/PKB is activated by phosphorylation of Thr 308 and Ser 473 residues of the kinase (8, 46, 52). The phosphorylation of Akt/PKB is dependent on phosphatidylinositol 3,4,5-triphosphate, a product of PI3K. Akt/PKB drives a major portion of the PI3K-mediated metabolic actions of insulin. Akt/PKB is required for insulinstimulated glucose uptake and glycogen synthesis (53). Akt/ PKB also promotes protein synthesis via activation of the mTOR-p70 S6 kinase pathway (19). Glycogen synthase kinase-3␤ (GSK-3␤), a negative regulator of glycogen synthase...

show abstract

Section: Methodsmentioning

confidence: 99%

Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle

Sugita

Kaneki²,

Sugita³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Fructosefeeding increases the activity of PI3-kinase (3) and has recently been shown to alter the phosphorylation of the regulatory subunit of PI3-kinase (45) in rat skeletal muscle. Therefore, we hypothesized that the PI3-kinase/Akt signaling pathway plays a major role in the fructose-induced upregulation of GLUT5 activity.…”

mentioning

confidence: 99%

Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway

Cui¹,

Schlesier²,

Fisher³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Cui, Xue-Lin, Anna M. Schlesier, Elda L. Fisher, Carla Cerqueira, and Ronaldo P. Ferraris. Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway. Am J Physiol Gastrointest Liver Physiol 288: G1310 -G1320, 2005. First published February 3, 2005 doi:10.1152/ajpgi.00550.2004.-Expression of rat glucose transporter-5 (GLUT5) is tightly regulated during development. Expression and activity are low throughout the suckling and weaning stages, but perfusion of the small intestinal lumen with fructose solutions during weaning precociously enhances GLUT5 activity and expression. Little is known, however, about the signal transduction pathways involved in the substrate-induced precocious GLUT5 development. We found that wortmannin and LY-294002, inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) specifically inhibited the increase in fructose uptake rate and brushborder GLUT5 protein abundance but not GLUT5 mRNA abundance. Perfusion of EGF, an activator of PI3-kinase, also resulted in a marked wortmannin-inhibitable increase in fructose uptake. Perfusion of fructose for 4 h increased cytosolic immunostaining of phosphatidylinositol-3,4,5-triphosphate (PIP 3), the primary product of PI3-kinase, mainly in the mid-to upper-villus regions in which the brush-border membrane also stained strongly with GLUT5. Perfusion of glucose for 4 h had little effect on fructose or glucose uptake and PIP 3 or GLUT5 staining. SH-5, an Akt inhibitor, prevented the increase in fructose uptake and GLUT5 protein induced by fructose solutions, and had no effect on glucose uptake. The PI3-kinase/Akt signaling pathway may be involved in the synthesis and/or recruitment to the brush border of GLUT5 transporters by luminal fructose in the small intestine of weaning rats. Increases in fructose transport during the critical weaning period when rats are shifting to a new diet may be modulated by several signaling pathways whose cross talk during development still needs to be elucidated. development; glucose; intestine; epidermal growth factor; mucosa BECAUSE OF DRAMATIC INCREASES in consumption of soft drinks and fruit juices, per capita consumption of fructose in the United States has increased by 10 times in 30 yr to almost 60 g fructose per day (4, 39). Paralleling this remarkable increase in fructose consumption is an alarming increase in incidence of obesity and in prevalence of type II diabetes (4,14). What makes this correlation disturbing is that per capita fructose consumption in very young children has increased faster than that of the general population and in the 1980s was already ϳ30 -40 g fructose per day representing 10% of their energy intake (39). The top 10th percentile of subjects in all age groups typically consume approximately two times more fructose, exposing this particular age group (1-6 yr of age) to potential metabolic derangements caused by excessive fructose consumption. There are very few studies on physiological adaptations to excessive fructose consumpti...

show abstract

“…In fact, β-endorphin can reverse insulin action by an activation of opioid μ-receptors to enhance the PI3-kinase/ Akt activity [8]. Thus, activation of opioid μ-receptor conferred a beneficial effect on insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin resistance is described as the reduced response of peripheral tissues to insulin [7]. Infusion of β-endorphin may improve insulin resistance in fructose-rich chow-fed rats [8]. Indeed, the induction of insulin resistance was more rapid in opioid μ-receptor knock-out mice than in wild-type mice [9].…”

Section: Introductionmentioning

confidence: 99%

Activation of opioid μ-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells

Tzeng

Liu²

2005

Diabetologia

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis: This study investigated the role of opioid μ-receptor activation in the improvement of insulin resistance. Methods: Myoblast C 2 C 12 cells were cultured with IL-6 to induce insulin resistance. Radioactive 2-deoxyglucose (2-DG) uptake was used to evaluate the effect of loperamide on insulin-stimulated glucose utilisation. Protein expression and phosphorylation in insulinsignalling pathways were detected by immunoblotting. Results: The insulin-stimulated 2-DG uptake was reduced by IL-6. Loperamide reversed this uptake, and the uptake was inhibited by blockade of opioid μ-receptors. Insulin resistance induced by IL-6 was associated with impaired expression of the insulin receptor (IR), IR tyrosine autophosphorylation, IRS-1 protein content and IRS-1 tyrosine phosphorylation. Also, an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase, Akt serine phosphorylation and the protein of glucose transporter subtype 4 were observed in insulin resistance. Loperamide reversed IL-6-induced decrement of these insulin signals. Conclusions/interpretation: Opioid μ-receptor activation may improve IL-6-induced insulin resistance through modulation of insulin signals to reverse the responsiveness of insulin. This provides a new target in the treatment of insulin resistance.

show abstract

Infusion of β-Endorphin Improves Insulin Resistance in Fructose-fed Rats

Cited by 33 publications

References 23 publications

Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle

Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle

Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway

Activation of opioid μ-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells

Contact Info

Product

Resources

About