Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase. Hunter RW, Hughey CC, Lantier L, Sundelin EI, Peggie M, Zeqiraj E, Sicheri F, Jessen N, Wasserman DH, Sakamoto K (2018) Nat Med 24: 1395-1406 Insulin signaling in alpha cells modulates glucagon secretion in vivo. Kawamori D, Kurpad AJ, Hu J, Liew CW, Shih JL, Ford EL, Herrera PL, Polonsky KS, McGuinness OP, Kulkarni RN (2009) Cell Metab 9: 350-61 Evidence that the brain of the conscious dog is insulin sensitive. Davis SN, Colburn C, Dobbins R, Nadeau S, Neal D, Williams P, Cherrington AD (1995) J Clin Invest 95: 593-602 Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis. Winnick JJ, Kraft G, Gregory JM, Edgerton DS, Williams P, Hajizadeh IA, Kamal MZ, Smith M, Farmer B, Scott M, Neal D, Donahue EP, Allen E, Cherrington AD (2016) J Clin Invest 126: 2236-48 Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs. Rivera N, Ramnanan CJ, An Z, Farmer T, Smith M, Farmer B, Irimia JM, Snead W, Lautz M, Roach PJ, Cherrington AD (2010) J Clin Invest 120: 4425-35 Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia. Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM, Kaestner KH (2001) Genes Dev 15: 1706-15 Opposing actions of Arx and Pax4 in endocrine pancreas development. Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P (2003) Genes Dev 17: 2591-603 Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP (2002) Am J Hum Genet 70: 604-11 Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW (2008) EMBO J 27: 1017-28 Central versus peripheral glucose sensing and the response to hypoglycemia. Cherrington AD (2008) Diabetes 57: 1158-9 Prevention of overt hypoglycemia during exercise: stimulation of endogenous glucose production independent of hepatic catecholamine action and changes in pancreatic hormone concentration. Coker RH, Koyama Y, Denny JC, Camacho RC, Lacy DB, Wasserman DH (2002) Diabetes 51: 1310-8 Effect of vagal cooling on the counterregulatory response to hypoglycemia induced by a low dose of insulin in the conscious dog. Cardin S, Jackson PA, Edgerton DS, Neal DW, Coffey CS, Cherrington AD (2001) Diabetes 50: 558-64 Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Gloyn AL, Noordam K, Willemsen MA, Ellard S, Lam WW, Campbell IW, Midgley P, Shiota C, Buettger C, Magnuson MA, Matschinsky FM, Hattersley AT (2003) Diabetes 52: 2433-40 Insulin sensitively controls the glucagon response to mild hypoglycemia in the dog. Igawa K, Mugavero M, Shiota M, Neal DW, Cherrington AD (2002) Diabetes 51: 3033-42 Pancreatic response to mild non-insulin-induced hypoglycemia does not involve extrinsic neural input. Sherck SM, Shiota M, Saccomando J, Cardin S, Allen EJ, Hastings JR, Neal DW, Williams PE, Cherrington AD (2001) Diabetes 50: 2487-96 Alpha- and beta-cell responses to small changes in plasma glucose in the conscious dog. Flattem N, Igawa K, Shiota M, Emshwiller MG, Neal DW, Cherrington AD (2001) Diabetes 50: 367-75 In the absence of counterregulatory hormones, the increase in hepatic glucose production during insulin-induced hypoglycemia in the dog is initiated in the liver rather than the brain. Connolly CC, Myers SR, Neal DW, Hastings JR, Cherrington AD (1996) Diabetes 45: 1805-13 The effects of differing insulin levels on the hormonal and metabolic response to equivalent hypoglycemia in normal humans. Davis SN, Goldstein RE, Jacobs J, Price L, Wolfe R, Cherrington AD (1993) Diabetes 42: 263-72 Counterregulation during hypoglycemia is directed by widespread brain regions. Frizzell RT, Jones EM, Davis SN, Biggers DW, Myers SR, Connolly CC, Neal DW, Jaspan JB, Cherrington AD (1993) Diabetes 42: 1253-61 Relationship between decrements in glucose level and metabolic response to hypoglycemia in absence of counterregulatory hormones in the conscious dog. Connolly CC, Adkins-Marshall BA, Neal DW, Pugh W, Jaspan JB, Cherrington AD (1992) Diabetes 41: 1308-19 Hypoglycemia in IDDM. Cryer PE, Binder C, Bolli GB, Cherrington AD, Gale EA, Gerich JE, Sherwin RS (1989) Diabetes 38: 1193-9 Role of brain in counterregulation of insulin-induced hypoglycemia in dogs. Biggers DW, Myers SR, Neal D, Stinson R, Cooper NB, Jaspan JB, Williams PE, Cherrington AD, Frizzell RT (1989) Diabetes 38: 7-16 Stimulation of glucose production through hormone secretion and other mechanisms during insulin-induced hypoglycemia. Frizzell RT, Hendrick GK, Brown LL, Lacy DB, Donahue EP, Carr RK, Williams PE, Parlow AF, Stevenson RW, Cherrington AD (1988) Diabetes 37: 1531-41 Role of gluconeogenesis in sustaining glucose production during hypoglycemia caused by continuous insulin infusion in conscious dogs. Frizzell RT, Hendrick GK, Biggers DW, Lacy DB, Donahue DP, Green DR, Carr RK, Williams PE, Stevenson RW, Cherrington AD (1988) Diabetes 37: 749-59 Contribution of the liver and extrasplanchnic tissues to the hypoglycemic action of dichloroacetate in the conscious dog. Diamond MP, Suhrer JH, Williams PE, Lacy WW, Cherrington AD (1982) Diabetes 31: 326-32 Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. Joy NG, Tate DB, Younk LM, Davis SN (2015) Diabetes 64: 2571-80 Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes. Gregory JM, Kraft G, Scott MF, Neal DW, Farmer B, Smith MS, Hastings JR, Allen EJ, Donahue EP, Rivera N, Winnick JJ, Edgerton DS, Nishimura E, Fledelius C, Brand CL, Cherrington AD (2015) Diabetes 64: 3439-51 Risk of Hypoglycemia Following Hospital Discharge in Patients With Diabetes and Acute Kidney Injury. Hung AM, Siew ED, Wilson OD, Perkins AM, Greevy RA, Horner J, Abdel-Kader K, Parr SK, Roumie CL, Griffin MR, Ikizler TA, Speroff T, Matheny ME (2018) Diabetes Care 41: 503-512 Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor. Harlan DM (2016) Diabetes Care 39: 1072-4 Mutants of glucokinase cause hypoglycaemia- and hyperglycaemia syndromes and their analysis illuminates fundamental quantitative concepts of glucose homeostasis. Davis EA, Cuesta-Muñoz A, Raoul M, Buettger C, Sweet I, Moates M, Magnuson MA, Matschinsky FM (1999) Diabetologia 42: 1175-86 Risk of hypoglycemia following intensification of metformin treatment with insulin versus sulfonylurea. Roumie CL, Min JY, Greevy RA, Grijalva CG, Hung AM, Liu X, Elasy T, Griffin MR (2016) CMAJ 188: E104-E112 Hypoglycemia-associated autonomic failure in healthy humans: comparison of two vs three periods of hypoglycemia on hypoglycemia-induced counterregulatory and symptom response 5 days later. Moheet A, Kumar A, Eberly LE, Kim J, Roberts R, Seaquist ER (2014) J Clin Endocrinol Metab 99: 664-70 The effects of insulin on the counterregulatory response to equivalent hypoglycemia in patients with insulin-dependent diabetes mellitus. Davis SN, Goldstein RE, Price L, Jacobs J, Cherrington AD (1993) J Clin Endocrinol Metab 77: 1300-7 Islet auto-transplantation into an omental or splenic site results in a normal beta cell but abnormal alpha cell response to mild non-insulin-induced hypoglycemia. Gustavson SM, Rajotte RV, Hunkeler D, Lakey JR, Edgerton DS, Neal DW, Snead WL, Penaloza AR, Cherrington AD (2005) Am J Transplant 5: 2368-77 Effects of hypoglycemia on functional magnetic resonance imaging response to median nerve stimulation in the rat brain. Kennan RP, Jacob RJ, Sherwin RS, Gore JC (2000) J Cereb Blood Flow Metab 20: 1352-9 Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Park SK, Dadak AM, Haase VH, Fontana L, Giaccia AJ, Johnson RS (2003) Mol Cell Biol 23: 4959-71 Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner. Suzuki R, Tobe K, Terauchi Y, Komeda K, Kubota N, Eto K, Yamauchi T, Azuma K, Kaneto H, Taguchi T, Koga T, German MS, Watada H, Kawamori R, Wright CV, Kajimoto Y, Kimura S, Nagai R, Kadowaki T (2003) J Biol Chem 278: 43691-8 Exendin-(9-39) corrects fasting hypoglycemia in SUR-1-/- mice by lowering cAMP in pancreatic beta-cells and inhibiting insulin secretion. De León DD, Li C, Delson MI, Matschinsky FM, Stanley CA, Stoffers DA (2008) J Biol Chem 283: 25786-93 Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism. Niswender KD, Shiota M, Postic C, Cherrington AD, Magnuson MA (1997) J Biol Chem 272: 22570-5 Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice. Irimia JM, Meyer CM, Peper CL, Zhai L, Bock CB, Previs SF, McGuinness OP, DePaoli-Roach A, Roach PJ (2010) J Biol Chem 285: 12851-61
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