Novel PEGylated basal insulin LY2605541 has a preferential hepatic effect on glucose metabolism

Diabetes

Volumn 63, Issue 2, 2014, Pages 494-504

  Moore, Mary Courtney ^a   Smith, Marta S ^a   Sinha, Vikram P ^b   Beals, John M ^b   Michael, M Dodson ^b   Jacober, Scott J ^b   Cherrington, Alan D ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; GLUCAGON; GLUCOSE; GLYCEROL; HUMAN INSULIN; INSULIN PEGLISPRO; SOMATOSTATIN; STAT3 PROTEIN; TRIACYLGLYCEROL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DRUG BLOOD LEVEL; GLUCAGON BLOOD LEVEL; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; INFUSION RATE; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN TREATMENT; LIMIT OF DETECTION; LIVER; LIVER BLOOD FLOW; LIVER FUNCTION; NONHUMAN; PORTAL VEIN BLOOD FLOW; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TRIACYLGLYCEROL BLOOD LEVEL; WESTERN BLOTTING;

ANIMALS; BLOOD GLUCOSE; DOGS; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN LISPRO; INSULINS; LACTIC ACID; LIVER; POLYETHYLENE GLYCOLS;

EID: 84893090167     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db13-0826     Document Type: Article

References (55)

1. Little S, Shaw J, Home P. Hypoglycemia rates with basal insulin analogs. Diabetes Technol Ther 2011;13(Suppl. 1):S53-S64
2. Bolli GB, Andreoli AM, Lucidi P. Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era. Diabetes Technol Ther 2011;13(Suppl. 1):S43-S52
3. Simon AC, DeVries JH. The future of basal insulin supplementation. Diabetes Technol Ther 2011;13(Suppl. 1):S103-S108
4. Heise T, Nosek L, Bøttcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab 2012;14:944-950
5. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res 2012;29:2104-2114
6. Birkeland KI, Home PD, Wendisch U, et al. Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care 2011;34:661-665
7. Bode BW, Buse JB, Fisher M, et al.; BEGIN Basal-Bolus Type 1 Trial Investigators. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med 2013;30:1293-1297
8. Pandyarajan V, Weiss MA. Design of non-standard insulin analogs for the treatment of diabetes mellitus. Curr Diab Rep 2012;12:697-704
9. Beals JM, Cutler GB, Doyle B, et al. PEGylated insulin lispro compounds. International Patent Application WO 2009/1521128 A1. 17 Dec 2009
10. Hansen RJ, Cutler GB Jr, Vick A, et al. LY2605541: leveraging hydrodynamic size to develop a novel basal insulin (Abstract). Diabetes 2012;61 (Suppl. 1):A228
11. Sinha VP, Howey DC, Soon DKW, et al. Single-dose pharmacokinetics (PK) and glucodynamics (GD) of the novel, long-acting basal insulin LY2605541 in healthy subjects (Abstract). Diabetes 2012;61(Suppl. 1):A273
12. Heise T, Howey DC, Sinha VP, Choi SL, Mace KF. Steady-state pharmacokinetics (PK) and glucodynamics (GD) of the novel, long-acting basal insulin LY2605541 dosed once-daily (QD) in patients with type 2 diabetes mellitus (T2DM). Diabetes 2012;61(Suppl. 1):A256
13. Bergenstal RM, Rosenstock J, Arakaki RF, et al. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care 2012;35:2140-2147
14. Rosenstock J, Bergenstal RM, Blevins TC, et al. Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study. Diabetes Care 2013;36:522-528
15. McGuinness OP, Fugiwara T, Murrell S, et al. Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog. Am J Physiol 1993;265:E314-E322
16. Wasserman DH, Lacy DB, Bracy D, Williams PE. Metabolic regulation in peripheral tissues and transition to increased gluconeogenic mode during prolonged exercise. Am J Physiol 1992;263:E345-E354
17. Winnick JJ, An Z, Moore MC, et al. A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin. Am J Physiol Endocrinol Metab 2009;297:E358-E366
18. Galassetti P, Chu CA, Neal DW, Reed GW, Wasserman DH, Cherrington AD. A negative arterial-portal venous glucose gradient increases net hepatic glucose uptake in euglycemic dogs. Am J Physiol 1999;277:E126-E134
19. Moore MC, Rossetti L, Pagliassotti MJ, et al. Neural and pancreatic influences on net hepatic glucose uptake and glycogen synthesis. Am J Physiol 1996;271:E215-E222
20. Ramnanan CJ, Saraswathi V, Smith MS, et al. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs. J Clin Invest 2011;121:3713-3723
21. Galassetti P, Shiota M, Zinker BA, Wasserman DH, Cherrington AD. A negative arterial-portal venous glucose gradient decreases skeletal muscle glucose uptake. Am J Physiol 1998;275:E101-E111
22. Edgerton DS, Ramnanan CJ, Grueter CA, et al. Effects of insulin on the metabolic control of hepatic gluconeogenesis in vivo. Diabetes 2009;58: 2766-2775
23. Mari A, Stojanovska L, Proietto J, Thorburn AW. A circulatory model for calculating non-steady-state glucose fluxes. Validation and comparison with compartmental models. Comput Methods Programs Biomed 2003;71: 269-281
24. Chap Z, Ishida T, Chou J, et al. First-pass hepatic extraction and metabolic effects of insulin and insulin analogues. Am J Physiol 1987;252:E209-E217
25. Sindelar DK, Balcom JH, Chu CA, Neal DW, Cherrington AD. A comparison of the effects of selective increases in peripheral or portal insulin on hepatic glucose production in the conscious dog. Diabetes 1996;45:1594-1604
26. Sindelar DK, Chu CA, Venson P, Donahue EP, Neal DW, Cherrington AD. Basal hepatic glucose production is regulated by the portal vein insulin concentration. Diabetes 1998;47:523-529
27. Coate KC, Kraft G, Lautz M, Smith M, Neal DW, Cherrington AD. A high-fat, high-fructose diet accelerates nutrient absorption and impairs net hepatic glucose uptake in response to a mixed meal in partially pancreatectomized dogs. J Nutr 2011;141:1643-1651
28. Sönksen PH, Russell-Jones D, Jones RH. Growth hormone and diabetes mellitus. A review of sixty-three years of medical research and a glimpse into the future? Horm Res 1993;40:68-79
29. Hopkins KD, Russell-Jones DL, Lehmann ED, Wheeler MJ, Sönksen PH. Intraperitoneal insulin affects insulin-like growth factor binding protein-1 in a well-controlled type I diabetic patient. Diabetes Care 1993;16:1404-1405
30. Shojaee-Moradie F, Powrie JK, Sundermann E, et al. Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans. Diabetes Care 2000;23:1124-1129
31. Avogaro A, Beltramello P, Gnudi L, et al. Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients. Evidence for a critical role of free fatty acids. Diabetes 1993;42: 1626-1634
32. Fanelli C, Calderone S, Epifano L, et al. Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans. J Clin Invest 1993;92:1617-1622
33. Lucidi P, Rossetti P, Porcellati F, et al. Mechanisms of insulin resistance after insulin-induced hypoglycemia in humans: the role of lipolysis. Diabetes 2010;59:1349-1357
34. Rivera N, Ramnanan CJ, An Z, et al. Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs. J Clin Invest 2010;120: 4425-4435
35. Connolly CC, Myers SR, Neal DW, Hastings JR, Cherrington AD. 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. Diabetes 1996;45:1805-1813
36. Jackson PA, Cardin S, Coffey CS, et al. Effect of hepatic denervation on the counterregulatory response to insulin-induced hypoglycemia in the dog. Am J Physiol Endocrinol Metab 2000;279:E1249-E1257
37. Jackson PA, Pagliassotti MJ, Shiota M, Neal DW, Cardin S, Cherrington AD. Effects of vagal blockade on the counterregulatory response to insulininduced hypoglycemia in the dog. Am J Physiol 1997;273:E1178-E1188
38. Rebrin K, Steil GM, Mittelman SD, Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest 1996;98:741-749
39. Sindelar DK, Chu CA, Rohlie M, Neal DW, Swift LL, Cherrington AD. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 1997;46:187-196
40. Moore MC, Smith MS, Turney MK, Boysen S, Williams PE. Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system. Diabetes Obes Metab 2011;13: 832-840
41. Linnebjerg H, Choi SL, Lam ECQ, Mace KF, Hodgson TS, Sinha VP. Pharmacokinetics (PK) of the novel, long-acting basal insulin LY2605541 in subjects with varying degrees of renal function (Abstract). Diabetes 2012; 61(Suppl. 1):A296
42. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol 2009;9(Suppl. 1):S3
43. Owens RA, Lockwood JF, Dunbar JD, et al. In vitro characterisation of novel basal insulin LY2605541: reduced mitogenicity and IGF-IR binding. Diabetologia 2012;55:120
44. Banks WA. Brain meets body: the blood-brain barrier as an endocrine interface. Endocrinology 2012;153:4111-4119
45. Banks WA, Broadwell RD. Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin, and albumin: pharmacokinetic and morphological assessments. J Neurochem 1994;62: 2404-2419
46. Broadwell RD, Sofroniew MV. Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol 1993;120:245-263
47. Kurtzhals P, Havelund S, Jonassen I, Kiehr B, Ribel U, Markussen J. Albumin binding and time action of acylated insulins in various species. J Pharm Sci 1996;85:304-308
48. Banks WA, Morley JE, Lynch JL, Lynch KM, Mooradian AD. Insulin detemir is not transported across the blood-brain barrier. Peptides 2010;31:2284-2288
49. Hennige AM, Sartorius T, Tschritter O, et al. Tissue selectivity of insulin detemir action in vivo. Diabetologia 2006;49:1274-1282
50. Inoue H, Ogawa W, Asakawa A, et al. Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. Cell Metab 2006;3:267-275
51. Ramnanan CJ, Kraft G, Smith MS, et al. Interaction between the central and peripheral effects of insulin in controlling hepatic glucose metabolism in the conscious dog. Diabetes 2013;62:74-84
52. Ramnanan CJ, Edgerton DS, Rivera N, et al. Molecular characterization of insulin-mediated suppression of hepatic glucose production in vivo. Diabetes 2010;59:1302-1311
53. Satake S, Moore MC, Igawa K, et al. Direct and indirect effects of insulin on glucose uptake and storage by the liver. Diabetes 2002;51:1663-1671
54. Baker M, Parton T. Kinetic determinants of hepatic clearance: plasma protein binding and hepatic uptake. Xenobiotica 2007;37:1110-1134
55. Braet F, Wisse E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp Hepatol 2002;1:1