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Dissecting the actions of widely used diabetes drugs

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  1. Miller, R.A. et al. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature advance online publication, doi:10.1038/nature11808 (6 January 2013).

  2. Jiang, G. & Zhang, B.B. Glucagon and regulation of glucose metabolism. Am. J. Physiol. Endocrinol. Metab. 284, E671–E678 (2003).

    Article  CAS  Google Scholar 

  3. Foretz, M. et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J. Clin. Invest. 120, 2355–2369 (2010).

    Article  CAS  Google Scholar 

  4. Unger, R.H. & Cherrington, A.D. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 122, 4–12 (2012).

    Article  CAS  Google Scholar 

  5. Braaten, J.T., Faloona, G.R. & Unger, R.H. The effect of insulin on the alpha-cell response to hyperglycemia in long-standing alloxan diabetes. J. Clin. Invest. 53, 1017–1021 (1974).

    Article  CAS  Google Scholar 

  6. Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001).

    Article  CAS  Google Scholar 

  7. Randle, P.J. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab. Rev. 14, 263–283 (1998).

    CAS  PubMed  Google Scholar 

  8. Shah, P. et al. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 85, 4053–4059 (2000).

    CAS  PubMed  Google Scholar 

  9. Cho, Y.M. et al. Targeting the glucagon receptor family for diabetes and obesity therapy. Pharmacol. Ther. 135, 247–278 (2012).

    Article  CAS  Google Scholar 

  10. Prince, M.J. Short-term treatment with glucagon receptor antagonist LY2409021 effectively reduces fasting blood glucose (FBG) and HbA(1c) in patients with type 2 diabetes mellitus. Diabetologia 54, S86 (2011).

    Google Scholar 

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Competing interests

A.D.C. is a consultant for Merck, Eli Lilly and Novo Nordisk. He also receives research support from Novo Nordisk and Eli Lilly. The other authors declare no conflict of interest.

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Dissecting the actions of widely used diabetes drugs. Nat Med 19, 272–273 (2013).

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