The insulin secretagogues glibenclamide and repaglinide do not influence growth hormone secretion in humans but stimulate glucagon secretion during profound insulin deficiency.
In vitro data have recently suggested that sulfonylureas (SUs) enhance GH secretion by modulating the effects of GHRH and somatostatin in pituitary cells. The present study was undertaken to explore in more detail a possible influence of a single dose of SU (glibenclamide) and a non-SU (repaglinide) insulin secretagogue on circulating GH dynamics. Ten C-peptide-negative type 1 diabetic individuals were examined on three occasions in random order. Either glibenclamide (10.5 mg), repaglinide (8 mg), or placebo was administered after overnight normalization of plasma glucose by iv insulin infusion. Subsequently, GH concentrations were measured regularly after stimulation with GHRH (bolus 0.1 micro g/kg) alone and during concomitant infusion with somatostatin (7 ng.kg(-1).min(-1)). Insulin was replaced at baseline levels (0.25 mU.kg(-1).min(-1)) and plasma glucose clamped at 5-6 mmol/liter. Overall, there were no significant statistical differences in GH responses determined as either GH peak concentrations, integrated levels of GH, or secretory burst mass of GH during the experimental protocol. In contrast, plasma glucagon concentrations were significantly increased during glibenclamide and repaglinide exposure. The present experimental design does not support the hypothesis that acute administration of pharmacological doses of the oral antihyperglycemic agents glibenclamide and repaglinide per se enhance GH release in humans. Additionally, this study shows that these potassium channel inhibitors seem to stimulate glucagon secretion in people who have severe intraislet insulin deficiency (e.g. type 1 diabetes). However, extrapolation of our findings to type 2 diabetic individuals should be done with some caution.
Østergård
Torben
T
Department of Medicine M (Endocrinology and Diabetes), University Hospital of Aarhus, DK-8000 Aarhus, Denmark. oest@dadlnet.dk
Degn
Kristine B
KB
Gall
Mari-Anne
MA
Carr
Richard D
RD
Veldhuis
Johannes D
JD
Thomsen
Mads K
MK
Rizza
Robert A
RA
Schmitz
Ole
O
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002219:Carbamates / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000008:administration & dosage*; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D010880:Piperidines / Q000008:administration & dosage*; D010919:Placebos; D026902:Potassium Channel Blockers; D013004:Somatostatin
D001786:Blood Glucose; D002096:C-Peptide; D002219:Carbamates; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D010919:Placebos; D026902:Potassium Channel Blockers; D019382:Human Growth Hormone; D013004:Somatostatin; C072379:repaglinide; D005934:Glucagon; D013007:Growth Hormone-Releasing Hormone; D005905:Glyburide