Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system

• Published in: Diabetes, obesity & metabolism Vol. 13; no. 9; pp. 832 - 840
• Main Authors: Moore, M. C., Smith, M. S., Turney, M. K., Boysen, S., Williams, P. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2011; Wiley Subscription Services, Inc
• Subjects: AKT protein; Animals; Arteries; Blood Glucose - drug effects; Central nervous system; Central Nervous System - drug effects; Central Nervous System - metabolism; Central Nervous System - pathology; Diabetes mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Dogs; Fatty acids; Glucagon; Glucose; Glucose Clamp Technique; Glucose metabolism; Head; hepatic glucose production; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Hypothalamus; Insulin; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - pharmacology; insulin analogues; Insulin Detemir; Insulin Glargine; insulin signalling; insulin therapy; Insulin, Long-Acting; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Obesity; Portal vein; Sampling; Somatostatin; STAT3; Stat3 protein; Tracers; Vertebrae
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2011.01418.x

Aims: 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 ([3‐3H]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 Rd 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.