title: Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system.
abstract: OBJECTIVE
  The effects of insulins detemir (Det) and glargine (Glar) on endogenous glucose production (EGP) and net hepatic glucose output (NHGO) were compared.
  
  
  METHODS
  Arteriovenous difference and tracer ([3-(3) H]glucose) techniques were employed during a two-step hyperinsulinemic euglycaemic clamp in conscious dogs (6 groups, n = 5-6/group). After equilibration and basal sampling (0-120 min), somatostatin was infused and basal glucagon was replaced intraportally. Det or Glar was infused via portal vein (Po), peripheral vein (IV), or bilateral carotid and vertebral arteries (H) at 0.1 and 0.3 mU/kg/min (low Insulin; Glar vs. Det, respectively, 120-420 min) and 4× the low insulin rate (high insulin; 420-540 min).
  
  
  RESULTS
  NHGO and EGP were suppressed and glucose R(d) and infusion rate were stimulated similarly by Det and Glar at both Low and high insulin with each infusion route. Non-esterified fatty acid (NEFA) concentrations during low insulin were 202 ± 37 versus 323 ± 75 µM in DetPo and GlarPo (p < 0.05) and 125 ± 39 versus 263 ± 48 µM in DetIV and GlarIV, respectively (p < 0.05). In DetH versus GlarH, pAkt/Akt (1.7 ± 0.2 vs. 1.0 ± 0.2) and pSTAT3/STAT3 (1.4 ± 0.2 vs. 1.0 ± 0.1) were significantly increased in the liver but not in the hypothalamus.
  
  
  CONCLUSIONS
  Det and Glar have similar net effects on acute regulation of hepatic glucose metabolism in vivo regardless of delivery route. Portal and IV detemir delivery reduces circulating NEFA to a greater extent than glargine, and head detemir infusion enhances molecular signalling in the liver. These findings indicate a need for further examination of Det's central and hepatic effects.
authors.affiliation: Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. genie.moore@vanderbilt.edu
authors.forename: M C
authors.initials: MC
authors.lastname: Moore
authors.forename: M S
authors.initials: MS
authors.lastname: Smith
authors.forename: M K
authors.initials: MK
authors.lastname: Turney
authors.forename: S
authors.initials: S
authors.lastname: Boysen
authors.forename: P E
authors.initials: PE
authors.lastname: Williams
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir