Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients.
Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbA1c 11.6 +/- 1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol x kg-1 x min-1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1 +/- 0.6 mmol/l). In all patients, insulin (by 17.4 +/- 4.7 nmol x 1-1 x min; p = 0.0157) and C-peptide (by 228.0 +/- 39.1 nmol x 1-1 x min; p = 0.0019) increased significantly over basal levels, glucagon was reduced (by -1418 +/- 308 pmol x 1-1 x min) and plasma glucose reached normal fasting concentrations (4.9 +/- 0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Nauck
M A
MA
Department of Medicine, Georg-August-University, Göttingen, Germany.
Kleine
N
N
Orskov
C
C
Holst
J J
JJ
Willms
B
B
Creutzfeldt
W
W
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting; D005260:Female; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide