Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery

Zuurbier, Coert J.; Hoek, Frans J.; Dijk, J. van; Abeling, N. G. G. M.; Meijers, Joost C. M.; Levels, J.H.M.; Jonge, Evert de; Mol, Bas A.J.M. de; Wezel, Harry B. van

doi:10.1093/bja/aen018

Cited by 27 publications

(13 citation statements)

References 40 publications

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“…Acute hyperglycemia often develops after trauma or major surgery, particularly surgery within the abdominal cavity (40), after severe burn injuries, or sepsis. If untreated, this condition, termed stressinduced hyperglycemia, contributes to mortality and delays healing in postsurgery and patients in intensive care units (41).…”

Section: Discussionmentioning

confidence: 99%

Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

Mullins¹,

Wang

Raje³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Anabolic and catabolic signaling oppose one another in adipose tissue to maintain cellular and organismal homeostasis, but these pathways are often dysregulated in metabolic disorders. Although it has long been established that stimulation of the β-adrenergic receptor inhibits insulin-stimulated glucose uptake in adipocytes, the mechanism has remained unclear. Here we report that β-adrenergic-mediated inhibition of glucose uptake requires lipolysis. We also show that lipolysis suppresses glucose uptake by inhibiting the mammalian target of rapamycin (mTOR) complexes 1 and 2 through complex dissociation. In addition, we show that products of lipolysis inhibit mTOR through complex dissociation in vitro. These findings reveal a previously unrecognized intracellular signaling mechanism whereby lipolysis blocks the phosphoinositide 3-kinase-Akt-mTOR pathway, resulting in decreased glucose uptake. This previously unidentified mechanism of mTOR regulation likely contributes to the development of insulin resistance.A dipose tissue plays an essential role in maintaining wholebody energy homeostasis by storing or releasing nutrients. This balance is controlled by opposing signaling pathways where anabolic processes are activated by insulin (INS) and catabolic actions are activated by catecholamines. An important unanswered question in adipose biology is how catecholamine-induced β-adrenergic signaling opposes insulin-stimulated glucose uptake (1-6). Surprisingly, the underlying mechanism for this wellestablished physiological response in adipocytes is still unknown.When nutrients are plentiful, insulin is released by the pancreas and stimulates the absorption of glucose and fatty acids in adipose tissue, where they are packaged and stored as triacylglycerol (TAG) in cellular lipid droplets. Insulin signaling in adipocytes is mediated by the phosphoinositide 3-kinase (PI3K)-Akt-mTOR pathway. mTOR is a highly conserved serine/threonine protein kinase that functions in either of two distinct multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 is defined primarily by the association of mTOR with raptor, whereas mTORC2 includes mTOR with rictor (7). Importantly, mTORC2 phosphorylation of Akt at S473 is required for Akt activity on AS160, which is necessary for glucose uptake in response to insulin (8-11). Of note, for both mTORC1 and mTORC2, the integrity of these protein complexes is essential for kinase substrate specificity and proper signaling (12, 13).During periods of fasting or stress, catecholamines are released by the sympathetic nervous system to activate lipolysis. Stimulation of the β-adrenergic receptor on adipocytes activates adenylyl cyclase (AC), leading to elevated cAMP and protein kinase A (PKA) activity. PKA initiates lipolysis by direct phosphorylation of hormone-sensitive lipase (HSL) and perilipin (14-16) and indirect activation of adipose triglyceride lipase (ATGL) (17-19). Lipolysis involves hydrolysis of TAG stored in the lipid droplet to produce diacylglycerol (DAG), mo...

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Section: Discussionmentioning

confidence: 99%

Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

Mullins¹,

Wang

Raje³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Immediately after blood sampling, rats were anesthetized in 4% isoflurane and additional blood samples were collected by cardiac puncture for determination of uric acid concentration and total antioxidant capacity. Since inhalational anesthetics are reported to substantially elevate the blood glucose level, separate blood samplings were needed for determination of all the planned parameters [30]. Serum samples were prepared by centrifugation and stored at –70°C until the analyses.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia

Hunyadi

Liktor‐Busa

Márki

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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The leaves of Morus alba L. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each other's important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevant in vitro and in vivo studies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel. In vivo antihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well as in vitro glucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents of M. alba (chlorogenic acid, rutin, isoquercitrin, and loliolide) were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.

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“…Glucose-insulin-potassium (GIK) therapy has been used in myocardial infarction, based on the assumption that GIK lowers circulating FFA levels, which are detrimental during cardiac reperfusion [38]. In experimental models of myocardial infarction and in patients having undergone heart surgery, acute stress promotes elevated serum levels of FFAs within 4-6 h after the insult, and the use of insulin has been shown to reduced those levels [38,39].…”

Section: Discussionmentioning

confidence: 99%

Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

et al. 2012

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Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery

Abstract: Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

Cited by 27 publications

References 40 publications

Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes

Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia

Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

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