Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in NIDDM.
OBJECTIVE
To investigate the effect of subcutaneously injected glucagon-like peptide 1 (GLP-1) (7-36)amide on postprandial plasma glucose, insulin, and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and a secondary failure to sulfonylureas.


METHODS
GLP-1 (25 nmol) was injected subcutaneously into either the abdominal wall or the gluteal region at a standardized depth and speed. The injection device was guided by the ultrasound determination of the depth of the fat layer. The peptide was given 5 min before a standard meal. Plasma concentrations of glucose, C-peptide, insulin, glucagon, and GLP-1 were followed during 240 min after the injection.


RESULTS
In control experiments, a significant hyperglycemia was attained after the meal. GLP-1 given into the abdominal wall not only virtually abolished the post-prandial blood glucose rise but significantly decreased glucose concentrations, with a nadir at approximately 25 min after the injection. A rapid rise of C-peptide and insulin levels was observed 10-15 min after the injection of GLP-1. The stimulatory effect of GLP-1 was transient, and, at 45 min after the meal, both insulin and C-peptide levels were almost identical in GLP-1 and control experiments. Significantly lower glucagon concentrations were observed 35-65 min after the peptide injection. GLP-1 concentration in plasma increased from 10 pM to a peak concentration (Cmax) of 70 pM at Tmax 30 min after injection. Then GLP-1 levels rapidly decreased to 25 pM at 95 min and returned to basal at 215 min. The gluteal injection of GLP-1 had similar effects compared with the abdominal administration on plasma levels of glucose, insulin, C-peptide, and glucagon.


CONCLUSIONS
GLP-1 is promptly absorbed from the subcutaneous tissue. It exerts a significant blood glucose lowering effect when administered before meals in overweight patients with NIDDM.
Gutniak
M K
MK
Department of Endocrinology, Karolinska Institute, Stockholm, Sweden.
Linde
B
B
Holst
J J
JJ
Efendić
S
S
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004435:Eating / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011863:Radioimmunoassay; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon