Efficacy, pharmacokinetics and tolerability of a somatostatin analogue (L-363,586) in insulin-dependent diabetes mellitus.
To assess the pharmacologic properties and possible use in the treatment of diabetes mellitus of a recently developed analogue somatostatin (L-363,586), the analogue (2, 5, 10 or 40 micrograms/hr), somatostatin (200 micrograms/hr), or placebo were infused intravenously for 5 hours in 6 insulin-dependent diabetic subjects who were given a standard meal containing xylose. The metabolic clearance rate of the analogue (approximately 300 ml/min) was 1/6 that previously reported for somatostatin (approximately 2000 ml/min) and its half-life was approximately 20 times as great as that reported for somatostatin (45 vs 2 min). At a dose of 10 micrograms/hr, the analogue produced suppression of plasma glucagon, growth hormone, glucose, xylose and triglyceride responses to meal ingestion which were comparable to those observed when somatostatin was infused at a rate of 200 micrograms/hr. We conclude that L-363,586 is a long-acting and potent analogue of somatostatin, which has the potential for use as an adjunct to insulin in the treatment of diabetes mellitus.
Gottesman
I
I
Tobert
J
J
Vandlen
R
R
Gerich
J
J
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005502:Food; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives; D014280:Triglycerides / Q000097:blood; D014994:Xylose / Q000097:blood
D001786:Blood Glucose; D010456:Peptides, Cyclic; D014280:Triglycerides; D013004:Somatostatin; C040968:seglitide; D013006:Growth Hormone; D005934:Glucagon; D014994:Xylose