Elevated NEFA levels impair glucose effectiveness by increasing net hepatic glycogenolysis

Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D (1984) Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects. J Clin Invest 74:1238–1246

DeFronzo RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687

Nagasaka S, Tokuyama K, Kusaka I et al (1999) Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach. Diabetes 48:1054–1060

Hawkins M, Gabriely I, Wozniak R, Reddy K, Rossetti L, Shamoon H (2002) Glycemic control determines hepatic and peripheral glucose effectiveness in type 2 diabetic subjects. Diabetes 51:2179–2189

Mevorach M, Giacca A, Aharon Y, Hawkins M, Shamoon H, Rossetti L (1998) Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus. J Clin Invest 102:744–753

Nielsen MF, Basu R, Wise S, Caumo A, Cobelli C, Rizza RA (1998) Normal glucose-induced suppression of glucose production but impaired stimulation of glucose disposal in type 2 diabetes: evidence for a concentration-dependent defect in uptake. Diabetes 47:1735–1747

Antras-Ferry J, Le Bigot G, Robin P, Robin D, Forest C (1994) Stimulation of phosphoenolpyruvate carboxykinase gene expression by fatty acids. Biochem Biophys Res Commun 203:385–391

Williamson JR, Kreisberg RA, Felts PW (1966) Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A 56:247–254

Kehlenbrink S, Tonelli J, Koppaka S, Chandramouli V, Hawkins M, Kishore P (2009) Inhibiting gluconeogenesis prevents fatty acid-induced increases in endogenous glucose production. Am J Physiol Endocrinol Metab 297:E165–E173

Kishore P, Tonelli J, Koppaka S et al (2006) Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes. Diabetes 55:1761–1768

Hawkins M, Tonelli J, Kishore P et al (2003) Contribution of elevated free fatty acid levels to the lack of glucose effectiveness in type 2 diabetes. Diabetes 52:2748–2758

Kishore P, Li W, Tonelli J, et al (2010) Adipocyte-derived factors potentiate nutrient-induced production of plasminogen activator inhibitor-1 by macrophages. Sci Transl Med 2: 20ra15

Finegood DT, Bergman RN, Vranic M (1987) Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates. Diabetes 36:914–924

Balent B, Goswami G, Goodloe G et al (2002) Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects. Ann N Y Acad Sci 967:535–543

Brooker HR, Mareci TH, Mao JT (1987) Selective Fourier transform localization. Magn Reson Med 5:417–433

Rossetti L, Chen W, Hu M, Hawkins M, Barzilai N, Efrat S (1997) Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele. Am J Physiol 273:E743–E750

Hovorka R, Jayatillake H, Rogatsky E, Tomuta V, Hovorka T, Stein DT (2007) Calculating glucose fluxes during meal tolerance test: a new computational approach. Am J Physiol Endocrinol Metab 293:E610–E619

Basu R, Barosa C, Basu A et al (2011) Transaldolase exchange and its effects on measurements of gluconeogenesis in humans. Am J Physiol Endocrinol Metab 300:E296–E303

Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996) Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest 98:378–385

Kishore P, Boucai L, Zhang K et al (2011) Activation of KATP channels suppresses glucose production in humans. J Clin Invest 121:4916–4920

Sikuler E, Polio J, Groszmann RJ, Hendler R (1987) Glucagon and insulin metabolism in a portal-hypertensive rat model. Am J Physiol 253:G110–G115

Jenssen T, Nurjhan N, Consoli A, Gerich JE (1990) Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration. J Clin Invest 86:489–497

Petersen KF, Laurent D, Rothman DL, Cline GW, Shulman GI (1998) Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans. J Clin Invest 101:1203–1209

Rossetti L, Giaccari A, Barzilai N, Howard K, Sebel G, Hu M (1993) Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes. J Clin Invest 92:1126–1134

Sindelar DK, Chu CA, Venson P, Donahue EP, Neal DW, Cherrington AD (1998) Basal hepatic glucose production is regulated by the portal vein insulin concentration. Diabetes 47:523–529

Aiston S, Andersen B, Agius L (2003) Glucose 6-phosphate regulates hepatic glycogenolysis through inactivation of phosphorylase. Diabetes 52:1333–1339

Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD (1988) Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 37:1020–1024

van de Werve G, Lange A, Newgard C, Mechin MC, Li Y, Berteloot A (2000) New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system. Eur J Biochem 267:1533–1549

Lam TK, van de Werve G, Giacca A (2003) Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites. Am J Physiol Endocrinol Metab 284:E281–E290

Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, Kraegen EW (1997) Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes 46:1768–1774

Roden M, Stingl H, Chandramouli V et al (2000) Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans. Diabetes 49:701–707

Stingl H, Krššák M, Krebs M et al (2001) Lipid-dependent control of hepatic glycogen stores in healthy humans. Diabetologia 44:48–54

Boden G, Chen X, Capulong E, Mozzoli M (2001) Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes. Diabetes 50:810–816

Shah P, Vella A, Basu A et al (2003) Elevated free fatty acids impair glucose metabolism in women. Diabetes 52:38–42

DeFronzo RA, Abdul-Ghani MA (2011) Preservation of beta-cell function: the key to diabetes prevention. J Clin Endocrinol Metab 96:2354–2366

Krssak M, Brehm A, Bernroider E et al (2004) Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes 53:3048–3056

Kacerovsky M, Jones J, Schmid AI et al (2011) Postprandial and fasting hepatic glucose fluxes in long-standing type 1 diabetes. Diabetes 60:1752–1758

Cline GW, Rothman DL, Magnusson I, Katz LD, Shulman GI (1994) 13C-nuclear magnetic resonance spectroscopy studies of hepatic glucose metabolism in normal subjects and subjects with insulin-dependent diabetes mellitus. J Clin Invest 94:2369–2376

Hwang JH, Perseghin G, Rothman DL et al (1995) Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. J Clin Invest 95:783–787

Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG (1990) Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322:223–228

Agius L (2008) Glucokinase and molecular aspects of liver glycogen metabolism. Biochem J 414:1–18

Agius L, Peak M, Newgard CB, Gomez-Foix AM, Guinovart JJ (1996) Evidence for a role of glucose-induced translocation of glucokinase in the control of hepatic glycogen synthesis. J Biol Chem 271:30479–30486

Clore JN, Stillman J, Sugerman H (2000) Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes. Diabetes 49:969–974

Caro JF, Triester S, Patel VK, Tapscott EB, Frazier NL, Dohm GL (1995) Liver glucokinase: decreased activity in patients with type II diabetes. Horm Metab Res 27:19–22

Seoane J, Gomez-Foix AM, O’Doherty RM, Gomez-Ara C, Newgard CB, Guinovart JJ (1996) Glucose 6-phosphate produced by glucokinase, but not hexokinase I, promotes the activation of hepatic glycogen synthase. J Biol Chem 271:23756–23760