Diabetes Metbolism — Enhanced fat oxidizing capacity Glucagon hormone injection, The correlations between the AUC of the insulin tolerance test and caecal Glucagon hormone injection of carbohydrage, glucose and mannose in the A. We defined intracellular glucosidase by their substrate described in the KEGG pathway map; those cleave phosphorylated carbohydrates were recognized as intracellular, and the rest of the genes were recognized to possess extracellular enzymatic activities.

Insulin and carbohydrate metabolism -

Effects of Insulin and Glucagon on Carbohydrate and Protein Metabolism of Adductor Muscle and Diaphragm Get access. PETERSON , RUTH D. Oxford Academic. Google Scholar. CLARISSA H. ROSE MARY BOCEK. Cite Cite RUTH D. Select Format Select format.

ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Endocrinology This issue Endocrine Society Journals Clinical Medicine Endocrinology and Diabetes Medicine and Health Books Journals Oxford Academic Enter search term Search.

Issue Section:. You do not currently have access to this article. Download all slides. Sign in Get help with access. Endocrine Society members Sign in through society site. Get help with access Institutional access Access to content on Oxford Academic is often provided through institutional subscriptions and purchases.

If you are a member of an institution with an active account, you may be able to access content in one of the following ways: IP based access Typically, access is provided across an institutional network to a range of IP addresses.

Sign in through your institution Choose this option to get remote access when outside your institution. Click Sign in through your institution.

Select your institution from the list provided, which will take you to your institution's website to sign in.

When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account. Following successful sign in, you will be returned to Oxford Academic. Sign in with a library card Enter your library card number to sign in.

Society Members Society member access to a journal is achieved in one of the following ways: Sign in through society site Many societies offer single sign-on between the society website and Oxford Academic.

When on the society site, please use the credentials provided by that society. Sign in using a personal account Some societies use Oxford Academic personal accounts to provide access to their members. Personal account A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.

Viewing your signed in accounts Click the account icon in the top right to: View your signed in personal account and access account management features. View the institutional accounts that are providing access.

Signed in but can't access content Oxford Academic is home to a wide variety of products. Institutional account management For librarians and administrators, your personal account also provides access to institutional account management.

Mol Cell Biol — Kubota N, Tobe K, Terauchi Y, Eto K, Yamauchi T, Suzuki R, Tsubamoto Y, Komeda K, Nakano R, Miki H, Satoh S, Sekihara H, Sciacchitano S, Lesniak M, Aizawa S, Nagai R, Kimura S, Akanuma Y, Taylor SI, Kadowaki T Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia.

Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF, Accili D Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS Taniguchi CM, Ueki K, Kahn R Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism.

J Clin Invest — Simmgen M, Knauf C, Lopez M, Choudhury AI, Charalambous M, Cantley J, Bedford DC, Claret M, Iglesias MA, Heffron H, Cani PD, Vidal-Puig A, Burcelin R, Withers DJ Liver-specific deletion of insulin receptor substrate 2 does not impair hepatic glucose and lipid metabolism in mice.

Dong X, Park S, Lin X, Copps K, Yi X, White MF Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. Razzini G, Ingrosso A, Brancaccio A, Sciacchitano S, Esposito DL, Falasca M Different subcellular localization and phosphoinositides binding of insulin receptor substrate protein pleckstrin homology domains.

Mol Endocrinol — Sawka-Verhelle D, Tartare-Deckert S, White MF, Van OE Insulin receptor substrate-2 binds to the insulin receptor through its phosphotyrosine-binding domain and through a newly identified domain comprising amino acids Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS Wolf G, Trub T, Ottinger E, Groninga L, Lynch A, White MF, Miyazaki M, Lee J, Shoelson SE PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities.

Cheatham B, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp 70 S6 kinase, DNA synthesis, and glucose transporter translocation.

CAS PubMed PubMed Central Google Scholar. Cell Metab — Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B Class IA phosphoinositide 3-kinases are obligate pp heterodimers. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD Phosphoinositide 3-kinases: a conserved family of signal transducers.

Trends Biochem Sci — Shepherd PR, Withers DJ, Siddle K Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J — Terauchi Y, Tsuji Y, Satoh S, Minoura H, Murakami K, Okuno A, Inukai K, Asano T, Kaburagi Y, Ueki K, Nakajima H, Hanafusa T, Matsuzawa Y, Sekihara H, Yin Y, Barrett JC, Oda H, Ishikawa T, Akanuma Y, Komuro I, Suzuki M, Yamamura K, Kodama T, Suzuki H, Yamamura K, Kodama T, Suzuki H, Koyasu S, Aizawa S, Tobe K, Fukui Y, Yazaki Y, Kadowaki T Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase.

Nat Genet — Ueki K, Yballe CM, Brachmann SM, Vicent D, Watt JM, Kahn CR, Cantley LC Increased insulin sensitivity in mice lacking p85beta subunit of phosphoinositide 3-kinase. Aoki K, Matsui J, Kubota N, Nakajima H, Iwamoto K, Takamoto I, Tsuji Y, Ohno A, Mori S, Tokuyama K, Murakami K, Asano T, Aizawa S, Tobe K, Kadowaki T, Terauchi Y Role of the liver in glucose homeostasis in PI 3-kinase p85alpha-deficient mice.

Brachmann SM, Ueki K, Engelman JA, Kahn RC, Cantley LC Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice.

Taniguchi CM, Tran TT, Kondo T, Luo J, Ueki K, Cantley LC, Kahn CR Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN.

Taniguchi CM, Aleman JO, Ueki K, Luo J, Asano T, Kaneto H, Stephanopoulos G, Cantley LC, Kahn CR The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance.

Logie L, Ruiz-Alcaraz AJ, Keane M, Woods YL, Bain J, Marquez R, Alessi DR, Sutherland C Characterization of a protein kinase B inhibitor in vitro and in insulin-treated liver cells. Tanti JF, Grillo S, Gremeaux T, Coffer PJ, Van OE, Le Marchand-Brustel Y Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.

Scheid MP, Marignani PA, Woodgett JR Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F, Hawkins PT Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B.

Cell — Liu P, Heng H, Roberts TM, Hao JJ Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov — Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB III, Kaestner KH, Bartolomei MS, Shulman GI, Birnbaum MJ Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 PKB beta.

Development — Dummler B, Tschopp O, Hynx D, Yang ZZ, Dirnhofer S, Hemmings BA Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies.

Brozinick JT Jr, Roberts BR, Dohm GL Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. Kim YB, Peroni OD, Franke TF, Kahn BB Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats.

Kahn CR Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 27 12 Suppl 2 — Paz K, Hemi R, LeRoith D, Karasik A, Elhanany E, Kanety H, Zick Y A molecular basis for insulin resistance.

Aguirre V, Uchida T, Yenush L, Davis R, White MF The c-Jun NH 2 -terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser Greene MW, Sakaue H, Wang L, Alessi DR, Roth RA Modulation of insulin-­stimulated degradation of human insulin receptor substrate-1 by Serine phosphorylation.

Zhang J, Gao Z, Yin J, Quon MJ, Ye J S6K directly phosphorylates IRS-1 on Ser to promote insulin resistance in response to TNF- alpha signaling through IKK2. Emanuelli B, Peraldi P, Filloux C, Chavey C, Freidinger K, Hilton DJ, Hotamisligil GS, Van OE SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-alpha in the adipose tissue of obese mice.

Ueki K, Kondo T, Kahn CR Suppressor of cytokine signaling 1 SOCS-1 and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Rui L, Yuan M, Frantz D, Shoelson S, White MF SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.

Liberman Z, Plotkin B, Tennenbaum T, Eldar-Finkelman H Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C betaII in the diabetic fat tissue. Liberman Z, Eldar-Finkelman H Serine phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 attenuates insulin signaling.

Kovacs P, Hanson RL, Lee YH, Yang X, Kobes S, Permana PA, Bogardus C, Baier LJ The role of insulin receptor substrate-1 gene IRS1 in type 2 diabetes in Pima Indians. Carlson CJ, Koterski S, Sciotti RJ, Poccard GB, Rondinone CM Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression.

Danielsson A, Ost A, Lystedt E, Kjolhede P, Gustavsson J, Nystrom FH, Stralfors P Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes.

FEBS J — Goodyear LJ, Giorgino F, Sherman LA, Carey J, Smith RJ, Dohm GL Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects.

Bjornholm M, Kawano Y, Lehtihet M, Zierath JR Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation.

Krook A, Bjornholm M, Galuska D, Jiang XJ, Fahlman R, Myers MG Jr, Wallberg-Henriksson H, Zierath JR Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Beeson M, Sajan MP, Dizon M, Grebenev D, Gomez-Daspet J, Miura A, Kanoh Y, Powe J, Bandyopadhyay G, Standaert ML, Farese RV Activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5- PO4 3 is defective in muscle in type 2 diabetes and impaired glucose tolerance: amelioration by rosiglitazone and exercise.

Rondinone CM, Carvalho E, Wesslau C, Smith UP Impaired glucose transport and protein kinase B activation by insulin, but not okadaic acid, in adipocytes from subjects with Type II diabetes mellitus.

Rondinone CM, Wang LM, Lonnroth P, Wesslau C, Pierce JH, Smith U Insulin receptor substrate IRS 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus.

Rieusset J, Bouzakri K, Chevillotte E, Ricard N, Jacquet D, Bastard JP, Laville M, Vidal H Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients.

Avruch J Insulin signal transduction through protein kinase cascades. Mol Cell Biochem — Matozaki T, Murata Y, Saito Y, Okazawa H, Ohnishi H Protein tyrosine phosphatase SHP a proto-oncogene product that promotes Ras activation.

Cancer Sci 10 — Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling.

Ravichandran KS, Lorenz U, Shoelson SE, Burakoff SJ Interaction of Shc with Grb2 regulates association of Grb2 with mSOS. Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ A Grb2-associated docking protein in EGF- and insulin-receptor signalling.

Baltensperger K, Kozma LM, Cherniack AD, Klarlund JK, Chawla A, Banerjee U, Czech MP Binding of the Ras activator son of sevenless to insulin receptor substrate-1 ­signaling complexes.

Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Dunn KL, Espino PS, Drobic B, He S, Davie JR The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.

Biochem Cell Biol — Roberts PJ, Der CJ Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene — Ma XM, Blenis J Molecular mechanisms of mTOR-mediated translational control. Hay N, Sonenberg N Upstream and downstream of mTOR.

Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N Amino acid regulation of TOR complex 1. Anjum R, Blenis J The RSK family of kinases: emerging roles in cellular signalling. Memmott RM, Dennis PA Akt-dependent and -independent mechanisms of mTOR regulation in cancer.

Cell Signal — Bouzakri K, Roques M, Gual P, Espinosa S, Guebre-Egziabher F, Riou JP, Laville M, Le Marchand-Brustel Y, Tanti JF, Vidal H Reduced activation of phosphatidylinositol-3 kinase and increased serine phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes.

Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Tremblay F, Gagnon A, Veilleux A, Sorisky A, Marette A Activation of the mammalian target of rapamycin pathway acutely inhibits insulin signaling to Akt and glucose transport in 3T3-L1 and human adipocytes.

Katz H, Butler P, Homan M, Zerman A, Caumo A, Cobelli C, Rizza R Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error.

Olson AL, Pessin JE Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. Annu Rev Nutr — Dentin R, Pegorier JP, Benhamed F, Foufelle F, Ferre P, Fauveau V, Magnuson MA, Girard J, Postic C Hepatic glucokinase is required for the synergistic action of ChREBP and SREBP-1c on glycolytic and lipogenic gene expression.

Sibrowski W, Seitz HJ Rapid action of insulin and cyclic AMP in the regulation of functional messenger RNA coding for glucokinase in rat liver. Kim SY, Kim HI, Kim TH, Im SS, Park SK, Lee IK, Kim KS, Ahn YH SREBP-1c mediates the insulin-dependent hepatic glucokinase expression.

Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, Shelton KD, Lindner J, Cherrington AD, Magnuson MA Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase.

Frame S, Cohen P GSK3 takes centre stage more than 20 years after its discovery. Imazu M, Strickland WG, Chrisman TD, Exton JH Phosphorylation and inactivation of liver glycogen synthase by liver protein kinases. Sharfi H, Eldar-Finkelman H Sequential phosphorylation of insulin receptor ­substrate-2 by glycogen synthase kinase-3 and c-Jun NH 2 -terminal kinase plays a role in hepatic insulin signaling.

MacAulay K, Doble BW, Patel S, Hansotia T, Sinclair EM, Drucker DJ, Nagy A, Woodgett JR Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Patel S, Doble BW, MacAulay K, Sinclair EM, Drucker DJ, Woodgett JR Tissue-specific role of glycogen synthase kinase 3beta in glucose homeostasis and insulin action.

Aiston S, Coghlan MP, Agius L Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. Eur J Biochem — Cohen P The twentieth century struggle to decipher insulin signalling. Munro S, Ceulemans H, Bollen M, Diplexcito J, Cohen PT A novel glycogen-­targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents.

Alemany S, Cohen P Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase FEBS Lett — Moorhead G, MacKintosh C, Morrice N, Cohen P Purification of the hepatic glycogen-associated form of protein phosphatase-1 by microcystin-Sepharose affinity chromatography.

Bollen M, Keppens S, Stalmans W Specific features of glycogen metabolism in the liver. Doherty MJ, Cadefau J, Stalmans W, Bollen M, Cohen PT Loss of the hepatic glycogen-binding subunit GL of protein phosphatase 1 underlies deficient glycogen synthesis in insulin-dependent diabetic rats and in adrenalectomized starved rats.

Lam TK, Carpentier A, Lewis GF, van de Werve G, Fantus IG, Giacca A Mechanisms of the free fatty acid-induced increase in hepatic glucose production. Physiol Rev — Schmoll D, Walker KS, Alessi DR, Grempler R, Burchell A, Guo S, Walther R, Unterman TG Regulation of glucosephosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR.

Evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity. Accili D Lilly lecture the struggle for mastery in insulin action: from triumvirate to republic. Puigserver P, Spiegelman BM Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha PGC-1 alpha : transcriptional coactivator and metabolic regulator.

Endocr Rev — Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction.

Zhang W, Patil S, Chauhan B, Guo S, Powell DR, Le J, Klotsas A, Matika R, Xiao X, Franks R, Heidenreich KA, Sajan MP, Farese RV, Stolz DB, Tso P, Koo SH, Montminy M, Unterman TG FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression.

Rena G, Guo S, Cichy SC, Unterman TG, Cohen P Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. Guo S, Rena G, Cichy S, He X, Cohen P, Unterman T Phosphorylation of serine by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence.

Zhang X, Gan L, Pan H, Guo S, He X, Olson ST, Mesecar A, Adam S, Unterman TG Phosphorylation of serine suppresses transactivation by FKHR FOXO1 by multiple mechanisms. Greer EL, Brunet A FOXO transcription factors at the interface between longevity and tumor suppression.

Matsuzaki H, Daitoku H, Hatta M, Tanaka K, Fukamizu A Insulin-induced phosphorylation of FKHR Foxo1 targets to proteasomal degradation. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM Control of hepatic gluconeogenesis through the transcriptional coactivator PGC Daitoku H, Yamagata K, Matsuzaki H, Hatta M, Fukamizu A Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR.

Hirota K, Sakamaki J, Ishida J, Shimamoto Y, Nishihara S, Kodama N, Ohta K, Yamamoto M, Tanimoto K, Fukamizu A A combination of HNF-4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucosephosphatase genes in response to fasting and feeding.

Dentin R, Liu Y, Koo SH, Hedrick S, Vargas T, Heredia J, Yates J III, Montminy M Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism.

Lewis GF, Zinman B, Groenewoud Y, Vranic M, Giacca A Hepatic glucose production is regulated both by direct hepatic and extrahepatic effects of insulin in humans.

Lewis GF, Vranic M, Harley P, Giacca A Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans. Lewis GF, Vranic M, Giacca A Glucagon enhances the direct suppressive effect of insulin on hepatic glucose production in humans. Lewis GF, Vranic M, Giacca A Role of free fatty acids and glucagon in the peripheral effect of insulin on glucose production in humans.

McCall RH, Wiesenthal SR, Shi ZQ, Polonsky K, Giacca A Insulin acutely suppresses glucose production by both peripheral and hepatic effects in normal dogs. Gupta N, Sandhu H, Goh T, Shah K, Wiesenthal SR, Yoshii H, Chong V, Lam TK, Haber CA, Williams W, Tchipashvili V, Giacca A Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia.

Pocai A, Lam TK, Gutierrez-Juarez R, Obici S, Schwartz GJ, Bryan J, Guilar-Bryan L, Rossetti L Hypothalamic K ATP channels control hepatic glucose production. Obici S, Zhang BB, Karkanias G, Rossetti L Hypothalamic insulin signaling is required for inhibition of glucose production.

Nat Med — Nat Neurosci — Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Buettner C, Camacho RC Hypothalamic control of hepatic glucose production and its potential role in insulin resistance.

Endocrinol Metab Clin North Am — Inoue H, Ogawa W, Asakawa A, Okamoto Y, Nishizawa A, Matsumoto M, Teshigawara K, Matsuki Y, Watanabe E, Hiramatsu R, Notohara K, Katayose K, Okamura H, Kahn CR, Noda T, Takeda K, Akira S, Inui A, Kasuga M Role of hepatic STAT3 in brain-insulin action on hepatic glucose production.

Inoue H, Ogawa W, Ozaki M, Haga S, Matsumoto M, Furukawa K, Hashimoto N, Kido Y, Mori T, Sakaue H, Teshigawara K, Jin S, Iguchi H, Hiramatsu R, LeRoith D, Takeda K, Akira S, Kasuga M Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo.

Am J Physiol Endocrinol Metab E29—E Isakoff SJ, Taha C, Rose E, Marcusohn J, Klip A, Skolnik EY The inability of phosphatidylinositol 3-kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin-stimulated glucose uptake.

Sano H, Kane S, Sano E, Miinea CP, Asara JM, Lane WS, Garner CW, Lienhard GE Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation.

Randhawa VK, Ishikura S, Talior-Volodarsky I, Cheng AW, Patel N, Hartwig JH, Klip A GLUT4 vesicle recruitment and fusion are differentially regulated by Rac, AS, and Rab8A in muscle cells.

Bandyopadhyay G, Standaert ML, Sajan MP, Karnitz LM, Cong L, Quon MJ, Farese RV Dependence of insulin-stimulated glucose transporter 4 translocation on 3-phosphoinositide-dependent protein kinase-1 and its target threonine in the activation loop of protein kinase C-zeta.

Bandyopadhyay G, Kanoh Y, Sajan MP, Standaert ML, Farese RV Effects of adenoviral gene transfer of wild-type, constitutively active, and kinase-defective protein kinase C-lambda on insulin-stimulated glucose transport in L6 myotubes.

Garvey WT, Maianu L, Zhu JH, Brechtel-Hook G, Wallace P, Baron AD Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance.

Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes.

N Engl J Med — Ren JM, Marshall BA, Mueckler MM, McCaleb M, Amatruda JM, Shulman GI Overexpression of Glut4 protein in muscle increases basal and insulin-stimulated whole body glucose disposal in conscious mice.

Kelley DE, Mokan M, Mandarino LJ Intracellular defects in glucose metabolism in obese patients with NIDDM. Kim YI, Lee FN, Choi WS, Lee S, Youn JH Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.

Bouskila M, Hirshman MF, Jensen J, Goodyear LJ, Sakamoto K Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Am J Physiol Endocrinol Metab E28—E Vaag A, Alford F, Henriksen FL, Christopher M, Beck-Nielsen H Multiple defects of both hepatic and peripheral intracellular glucose processing contribute to the hyperglycaemia of NIDDM.

Nikoulina SE, Ciaraldi TP, Mudaliar S, Mohideen P, Carter L, Henry RR Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. Dokken BB, Henriksen EJ Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats.

Krssak M, Falk PK, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.

Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats.

Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI Mitochondrial dysfunction in the elderly: possible role in insulin resistance.

Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. Rasmussen BB, Holmback UC, Volpi E, Morio-Liondore B, Paddon-Jones D, Wolfe RR Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle.

Gaster M, Beck-Nielsen H Triacylglycerol accumulation is not primarily affected in myotubes established from type 2 diabetic subjects. Biochim Biophys Acta — Morino K, Petersen KF, Shulman GI Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction.

Diabetes 55 Suppl 2 :S9—S Samuel VT, Liu ZX, Wang A, Beddow SA, Geisler JG, Kahn M, Zhang XM, Monia BP, Bhanot S, Shulman GI Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease.

Befroy DE, Petersen KF, Dufour S, Mason GF, de Graaf RA, Rothman DL, Shulman GI Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients.

Turner N, Heilbronn LK Is mitochondrial dysfunction a cause of insulin resistance? Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance.

Galgani JE, Moro C, Ravussin E Metabolic flexibility and insulin resistance. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, Bain J, Stevens R, Dyck JR, Newgard CB, Lopaschuk GD, Muoio DM Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.

Bandyopadhyay G, Standaert ML, Kikkawa U, Ono Y, Moscat J, Farese RV Effects of transiently expressed atypical zeta, lambda , conventional alpha, beta and novel delta, epsilon protein kinase C isoforms on insulin-stimulated translocation of epitope-tagged GLUT4 glucose transporters in rat adipocytes: specific interchangeable effects of protein kinases C-zeta and C-lambda.

Ducluzeau PH, Fletcher LM, Vidal H, Laville M, Tavare JM Molecular mechanisms of insulin-stimulated glucose uptake in adipocytes. Diab Metab — Watson RT, Kanzaki M, Pessin JE Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes.

Mol Biol Cell — Chiang SH, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL, Macara IG, Pessin JE, Saltiel AR Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver.

Shoelson SE, Lee J, Goldfine AB Inflammation and insulin resistance. Lewis GF, Carpentier A, Adeli K, Giacca A Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Kershaw EE, Flier JS Adipose tissue as an endocrine organ. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance.

Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.

Biochem Biophys Res Commun — Nieto-Vazquez I, Fernandez-Veledo S, de Alvero C, Lorenzo M Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle.

Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. Schmitz-Peiffer C, Browne CL, Oakes ND, Watkinson A, Chisholm DJ, Kraegen EW, Biden TJ Alterations in the expression and cellular localization of protein kinase C isozymes epsilon and theta are associated with insulin resistance in skeletal muscle of the high-fat-fed rat.

Perseghin G, Petersen K, Shulman GI Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 27 Suppl 3 :S6—S Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 IRS-1 -associated phosphatidylinositol 3-kinase activity in muscle.

Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.

Itani SI, Ruderman NB, Schmieder F, Boden G Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha.

Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease.

Talior I, Tennenbaum T, Kuroki T, Eldar-Finkelman H PKC-delta-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase. Kamata H, Manabe T, Oka S, Kamata K, Hirata H Hydrogen peroxide activates IkappaB kinases through phosphorylation of serine residues in the activation loops.

Wang X, Martindale JL, Liu Y, Holbrook NJ The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival.

Ravichandran LV, Esposito DL, Chen J, Quon MJ Protein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin. Bollag GE, Roth RA, Beaudoin J, Mochly-Rosen D, Koshland DE Jr Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity.

Lam TK, Yoshii H, Haber CA, Bogdanovic E, Lam L, Fantus IG, Giacca A Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta. Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver.

Evans JL, Goldfine ID, Maddux BA, Grodsky GM Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes —8. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB.

Yin MJ, Yamamoto Y, Gaynor RB The anti-inflammatory agents aspirin and salicylate inhibit the activity of I kappa B kinase-beta. Kopp E, Ghosh S Inhibition of NF-kappa B by sodium salicylate and aspirin. Fleischman A, Shoelson SE, Bernier R, Goldfine AB Salsalate improves glycemia and inflammatory parameters in obese young adults.

Gilgore SG, Rupp JJ Response of blood glucose to intravenous salicylate. Metab Clin Exp — Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes.

Kim JK, Kim YJ, Fillmore JJ, Chen Y, Moore I, Lee J, Yuan M, Li ZW, Karin M, Perret P, Shoelson SE, Shulman GI Prevention of fat-induced insulin resistance by salicylate.

Xiao C, Giacca A, Lewis GF The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and Beta-cell dysfunction in overweight and obese nondiabetic men.

Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M IKK-beta links inflammation to obesity-induced insulin resistance. Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ, Ye J Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex.

Seifert R, Schachtele C, Rosenthal W, Schultz G Activation of protein kinase C by cis- and trans-fatty acids and its potentiation by diacylglycerol. Ghosh S, Baltimore D Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS TLR4 links innate immunity and fatty acid-induced insulin resistance.

Evans JL, Goldfine ID, Maddux BA, Grodsky GM Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes.

Solinas G, Naugler W, Galimi F, Lee MS, Karin M Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS A central role for JNK in obesity and insulin resistance.

Kaneto H, Nakatani Y, Miyatsuka T, Kawamori D, Matsuoka TA, Matsuhisa M, Kajimoto Y, Ichijo H, Yamasaki Y, Hori M Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide. Nakatani Y, Kaneto H, Kawamori D, Hatazaki M, Miyatsuka T, Matsuoka TA, Kajimoto Y, Matsuhisa M, Yamasaki Y, Hori M Modulation of the JNK pathway in liver affects insulin resistance status.

Yang R, Wilcox DM, Haasch DL, Jung PM, Nguyen PT, Voorbach MJ, Doktor S, Brodjian S, Bush EN, Lin E, Jacobson PB, Collins CA, Landschulz KT, Trevillyan JM, Rondinone CM, Surowy TK Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice.

Kumashiro N, Tamura Y, Uchida T, Ogihara T, Fujitani Y, Hirose T, Mochizuki H, Kawamori R, Watada H Impact of oxidative stress and peroxisome proliferator-activated receptor gamma coactivator-1alpha in hepatic insulin resistance.

Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C—dependent activation of NAD P H oxidase in cultured vascular cells.

Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.

Hung JH, Su IJ, Lei HY, Wang HC, Lin WC, Chang WT, Huang W, Chang WC, Chang YS, Chen CC, Lai MD Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-kappaB and pp 38 mitogen-activated protein kinase.

Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM, Ron D An integrated stress response regulates amino acid metabolism and resistance to oxidative stress.

Wolf, ibid. Anderson and Carruthers have also found that the polarimetric value of dialysates or extracts of blood varies according to the reaction of the solution at the time of estimation. Reprints and permissions. Insulin and Carbohydrate Metabolism.

Nature , — Download citation. Issue Date : 18 February Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Skip to main content Thank you for visiting nature. nature news article.

Insulin and carbohydrate metabolism discovery of carnohydrate nearly a century ago revolutionized the Insupin of diabetes mellitus, carbohyrrate type 1 mdtabolism mellitus T1DMIneulin initiated extensive Insulin and carbohydrate metabolism into the effects of insulin. At approximately carbohydratte same time, Imsulin was Insulin and carbohydrate metabolism that patients with cancer were characterized by Immune-boosting essential oils intolerance and impaired insulin sensitivity cwrbohydrate glucose metabolism has been subsequently found in cancer [1, 2]. Insulin, a peptide hormone produced by the β cells in the pancreas, is anabolic, as it stimulates synthesis of glycogen, protein, and triglycerides and it suppresses glucose production by the body, while stimulating glucose uptake from the circulation [3]. Moreover, insulin action is tissue-specific, since it depends on the binding of insulin to its cell-surface receptor. The insulin receptor, which is composed of two transmembrane β chains and two extracellular α chains, has intrinsic tyrosine kinase activity [4, 5] and binding of insulin to its receptor initiates a signaling cascade characterized by phosphorylation events and genomic effects. When Glucagon hormone injection eat a Glucagon hormone injection containing carbohydrates, the digestive metaboljsm Glucagon hormone injection down the merabolism ones into sugar, which enters the blood. Chronic hyperglycemia and inflammation carbohydrates are composed of sugars such as fructose Insjlin glucose which have Glucagon hormone injection chemical structures composed of only one carnohydrate Glucagon hormone injection or two sugars disaccharides. Simple carbohydrates metabolsim easily and quickly utilized for energy by the metabolims because of their simple chemical structure, often leading to a faster rise in blood sugar and insulin secretion from the pancreas — which can have negative health effects. These carbohydrates have more complex chemical structures, with three or more sugars linked together known as oligosaccharides and polysaccharides. Many complex carbohydrate foods contain fiber, vitamins and minerals, and they take longer to digest — which means they have less of an immediate impact on blood sugar, causing it to rise more slowly. But other so called complex carbohydrate foods such as white bread and white potatoes contain mostly starch but little fiber or other beneficial nutrients. Dividing carbohydrates into simple and complex, however, does not account for the effect of carbohydrates on blood sugar and chronic diseases.