115
Views
12
CrossRef citations to date
0
Altmetric
Perspective

Obesity, insulin resistance, Type 2 diabetes and free fatty acids

Pages 499-505 | Published online: 10 Jan 2014

References

  • Bray GA. Medical consequences of obesity. J. Clin. Endocrinol. Metab.89, 2583–2589 (2004).
  • Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes46, 3–10 (1997).
  • Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. JAMA294, 334–341 (2005).
  • Weyer C, Funahashi T, Tanaka et al. Hypoadiponectinemia in obesity and Type 2 diabetes: a close association with insulin resistance and hyperinsulinemia. J. Clin. Endocrinol. Metab.88, 1930–1935 (2001).
  • Yang WS, Lee WJ, Funahashi T et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J. Clin. Endocrinol. Metab.86, 3815–3819 (2001).
  • Reaven GM, Hollenbeck C, Jeng C-Y, Wu MS, Chen YD. Measurement of plasma glucose, free fatty acid, lactate and insulin for 24 h in patients with NIDDM. Diabetes37, 1020–1024 (1988).
  • Boden G, Jadali F, White J et al. Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J. Clin. Invest.88, 960–966 (1991).
  • Santomauro AT, Boden G, Silva ME et al. Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes48, 1836–1841 (1999).
  • Bjorntorp P, Bergman H, Varnauskas E. Plasma free fatty acid turnover in obesity. Acta. Med. Scand.185, 351–356 (1969).
  • Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM. Influence of body fat distribution on free fatty acid metabolism obesity. J. Clin. Invest.83, 1168–1173 (1989).
  • Boden G, Cheung P, Stein TP, Kresge K, Mozzoli M. FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis. Am. J. Physiol.283, E12–E19 (2002).
  • Baron AD. Insulin resistance and vascular function. J. Diabetes Complications16, 92–102 (2002).
  • Zeng G, Nystrom FH, Ravichandran LV et al. Roles for insulin receptor, PI3-kinase and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation101, L1539–L1545 (2000).
  • Steinberg HO, Tarshoby M, Monestel R et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J. Clin. Invest.100, 1230–1239 (1997).
  • Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose-fatty acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet1, 785–789 (1963).
  • Boden G, Chen X. Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. J. Clin. Invest.96, 1261–1268 (1995).
  • Dresner A, Laurent D, Marcucci M et al. Effects of free fatty acids on glucose transport and IRS-1 associated phosphatidylinositol 3-kinase activity. J. Clin. Invest.103, 253–259 (1999).
  • Boden G, Lebed B, Schatz M, Homko C, Semieux S. Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes50, 1612–1617 (2001).
  • Itani SI, Ruderman NB, Schmieder, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes51, 2005–2011 (2002).
  • Farese R. Diabetes Mellitus: a Fundamental and Clinical Text. LeRoith D, Taylor SI, Olefsky JM (Eds). Philadelphia, Lippincott, 239–251 (2000).
  • Yu C, Chen Y, Cline GW et al. Mechanism by which fatty acids inhibit activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem.277, 50230–50236 (2002).
  • Boden G, She P, Mozzoli M et al. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver. Diabetes54, 3458–3465 (2005).
  • Inoguchi T, Li P, Umeda F et al. 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. Diabetes49, 1939–1945 (2000).
  • Benjamin SM, Valdez R, Geiss LS, Rolka DB, Narayan KM. Estimated number of adults with prediabetes in the US in 2000: opportunities for prevention. Diabetes Care26, 645–649 (2003).
  • Boden G. Free fatty acids and insulin secretion in humans. Current Diabetes Reports5, 167–170 (2005).
  • Crespin SR, Greenough WB, Steinberg D. Stimulation of insulin secretion by longchain free fatty acids. J. Clin. Invest.52, 1979–1984 (1973).
  • Hennes MMI, Dua A, Kissebah AH. Effects of free fatty acids and glucose on splanchnic insulin dynamics. Diabetes46, 57–62 (1997).
  • Balent B, Goswami G, Goodloe G et al. Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects. Ann. NY. Acad. Sci.967, 535–543 (2002).
  • Brown AJ, Jupe S, Briscoe CP. A family of fatty acid binding receptors. DNA Cell Biol.24, 54–61 (2005).
  • Boden G, Chen X, Rosner J, Barton M. Effects of a 48-h fat infusion on insulin secretion and glucose utilization. Diabetes44, 1239–1242 (1995).
  • Jensen CB, Storgaard H, Holst JJ, Dela F, Madsbad S, Vaag AA. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men. J. Clin. Endocrinol. Metab.88, 2775–2783 (2003).
  • Kashyap S, Belfort R, Gastaldelli A et al. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop Type 2 diabetes. Diabetes52, 2461–2474 (2003).
  • Boden G, Chen X, Iqbal N. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetes and nondiabetic subjects. Diabetes47, 1609–1612 (1998).
  • Dobbins RL, Chester MW, Daniels MB, McGarry DJ, Stein DT. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. Diabetes47, 1613–1618 (1998).
  • Boden G, Soeldner JS, Gleason RE, Marble A. Elevated serum human growth hormone and decreased serum insulin in prediabetic males after intravenous tolbutamide and glucose. J. Clin. Invest.47, 729–739 (1968).
  • Stogaard H, Jensen CB, Vaag A et al. Insulin secretion after short- and long-term low grade free fatty acid infusion in men with increased risk of developing Type 2 diabetes. Metabolism52, 885–894 (2003).
  • Boden G, Chen X. Effects of fatty acids and ketone bodies on basal insulin secretion in Type 2 diabetes. Diabetes48, 577–583 (1999).
  • Hirose H, Lee YH, Inman LR, Nagasawa Y, Johnson JH, Unger RH. Defective fatty acid mediated β-cell compensation in Zucker diabetic fatty rats. J. Biol. Chem.271, 5633–5637 (1996).
  • Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes44, 863–870 (1995).
  • El-Assaad W, Buteau J, Peyot ML et al. Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death. Endocrinology144, 4154–4163 (2003).
  • Tataranni PA, Ortega E. A burning question. Does an adipokines-induced activation of the immune system mediate the effect of overnutrition on Type 2 diabetes? Diabetes54, 917–927 (2005).
  • Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and system insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med.11, 183–190 (2005).
  • Xu H, Barnes GT, Yang Q et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest.112, 1821–1830 (2003).
  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest.112, 1796–1808 (2003).
  • Fuccella LM, Goldaniga G, Lovisolo P et al. Inhibition of lipolysis by nicotinic acid and by acipimox. Clin. Pharmacol. Ther.28, 790–795 (1980).
  • Chen X, Iqbal N, Boden G. The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects. J. Clin. Invest.103, 365–372 (1999).
  • Boden G, Cheung P, Mozzoli M, Fried SK. Effect of thiazolidinediones on glucose and fatty acid metabolism in patients with Type 2 diabetes. Metabolism52, 753–759 (2003).
  • Boden G, Homko C, Mozzoli M, Showe LC, Nichols C, Cheung P. Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes54, 880–885 (2005).
  • Ghazzi MN, Perez JE, Antonucci TK et al. Cardiac and glycemic benefits of troglitazone treatment in NIDDM: the Troglitazone Study Group. Diabetes46, 433–439 (1997).
  • Maggs DG, Buchanan TA, Burant CF et al. Metabolic effects of troglitazone monotherapy in Type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med.128, 176–185 (1998).
  • Mayerson AB, Hundal RS, Dufour S. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with Type 2 diabetes. Diabetes51, 797–802 (2002).
  • Berger J, Moller DE. The mechanisms of action of PPARs. Ann. Rev. Med.53, 409–435 (2002).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.