Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Pharmacology |
| Vol/bind | 451 |
| Udgave nummer | 2 |
| Sider (fra-til) | 217-25 |
| Antal sider | 8 |
| ISSN | 0014-2999 |
| Status | Udgivet - 2002 |
Bibliografisk note
Keywords: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Hypoglycemic Agents; Insulin; Male; Peptide Fragments; Protein Precursors; Swine, MiniatureBiblioteksadgang?
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I: European Journal of Pharmacology, Bind 451, Nr. 2, 2002, s. 217-25.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - NN2211: a long-acting glucagon-like peptide-1 derivative with anti-diabetic effects in glucose-intolerant pigs.
AU - Ribel, Ulla
AU - Larsen, Marianne O
AU - Rolin, Bidda
AU - Carr, Richard D
AU - Wilken, Michael
AU - Sturis, Jeppe
AU - Westergaard, Lisbet
AU - Deacon, Carolyn F
AU - Knudsen, Lotte Bjerre
N1 - Keywords: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Hypoglycemic Agents; Insulin; Male; Peptide Fragments; Protein Precursors; Swine, Miniature
PY - 2002
Y1 - 2002
N2 - Glucagon-like peptide-1 (GLP-1) is an effective anti-diabetic agent, but its metabolic instability makes it therapeutically unsuitable. This study investigated the pharmacodynamics of a long-acting GLP-1 derivative (NN2211: (Arg(34)Lys(26)-(N- epsilon -(gamma-Glu(N-alpha-hexadecanoyl)))-GLP-1(7-37)), after acute and chronic treatment in hyperglycaemic minipigs. During hyperglycaemic glucose clamps, NN2211 (2 micrograms kg(-1) i.v.) treated pigs required more (P < 0.005) glucose than control animals (5.8 +/- 2.1 vs. 2.9 +/- 1.8 mg kg(-1) min(-1)). Insulin excursions were higher (P < 0.01) after NN2211 (15,367 +/- 5,438 vs. 9,014 +/- 2,952 pmol l(-1) min), and glucagon levels were suppressed (P < 0.05). Once-daily injections of NN2211 (3.3 micrograms kg(-1) s.c.) reduced the glucose excursion during an oral glucose tolerance test, to 59 +/- 15% of pre-treatment values by 4 weeks (P < 0.05), without measurable changes in insulin responses. Fructosamine concentrations were unaltered by vehicle, but decreased (from 366 +/- 187 to 302 +/- 114 micromol l(-1), P = 0.14) after 4 weeks of NN2211. Gastric emptying was reduced (P < 0.05) by NN2211. NN2211 acutely increases glucose utilization during a hyperglycaemic glucose clamp and chronic treatment results in better daily metabolic control. Therefore, NN2211, a GLP-1 derivative that can be administered once daily, holds promise as a new anti-diabetic drug with a minimal risk of hypoglycaemia.
AB - Glucagon-like peptide-1 (GLP-1) is an effective anti-diabetic agent, but its metabolic instability makes it therapeutically unsuitable. This study investigated the pharmacodynamics of a long-acting GLP-1 derivative (NN2211: (Arg(34)Lys(26)-(N- epsilon -(gamma-Glu(N-alpha-hexadecanoyl)))-GLP-1(7-37)), after acute and chronic treatment in hyperglycaemic minipigs. During hyperglycaemic glucose clamps, NN2211 (2 micrograms kg(-1) i.v.) treated pigs required more (P < 0.005) glucose than control animals (5.8 +/- 2.1 vs. 2.9 +/- 1.8 mg kg(-1) min(-1)). Insulin excursions were higher (P < 0.01) after NN2211 (15,367 +/- 5,438 vs. 9,014 +/- 2,952 pmol l(-1) min), and glucagon levels were suppressed (P < 0.05). Once-daily injections of NN2211 (3.3 micrograms kg(-1) s.c.) reduced the glucose excursion during an oral glucose tolerance test, to 59 +/- 15% of pre-treatment values by 4 weeks (P < 0.05), without measurable changes in insulin responses. Fructosamine concentrations were unaltered by vehicle, but decreased (from 366 +/- 187 to 302 +/- 114 micromol l(-1), P = 0.14) after 4 weeks of NN2211. Gastric emptying was reduced (P < 0.05) by NN2211. NN2211 acutely increases glucose utilization during a hyperglycaemic glucose clamp and chronic treatment results in better daily metabolic control. Therefore, NN2211, a GLP-1 derivative that can be administered once daily, holds promise as a new anti-diabetic drug with a minimal risk of hypoglycaemia.
M3 - Journal article
C2 - 12231394
SN - 0014-2999
VL - 451
SP - 217
EP - 225
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -