Indomethacin decreases insulin secretion in patients with type 2 diabetes mellitus.
In healthy subjects, basal endogenous glucose production (EGP) is partly regulated by paracrine intrahepatic factors. Administration of indomethacin, an inhibitor of prostaglandin synthesis, resulted in a transient stimulation of EGP without changes in glucoregulatory hormone concentrations. It is unknown whether similar paracrine factors influence basal EGP in type 2 diabetes mellitus. The effects of 150 mg indomethacin, a nonendocrine stimulator of glucose production in healthy adults, and placebo on EGP were measured in a randomized placebo-controlled study in patients with type 2 diabetes mellitus (3 men and 3 women; mean age, 58.5 years; mean body mass index, 28.6 kg x m(-2)). EGP was measured before and for 6 hours after administration of placebo/indomethacin, by a primed, continuous infusion of [6,6-2H2]glucose. After indomethacin, plasma glucose and EGP increased in all subjects by 14% (P < .05) and 48% (P < .05), respectively. In the control experiment, plasma glucose and EGP declined gradually in all subjects by 22% (P < .001) and 17% (P = .004), respectively. The stimulation of glucose production coincided with the inhibition of insulin secretion by 52% within 1 hour after administration of indomethacin (P < .001). In the control experiment, insulin secretion decreased gradually by 18% after 6 hours (P < .001). Thus, indomethacin inhibits insulin secretion and stimulates EGP in type 2 diabetes.
Pereira Arias
A M
AM
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
Romijn
J A
JA
Corssmit
E P
EP
Ackermans
M T
MT
Nijpels
G
G
Endert
E
E
Sauerwein
H P
HP
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D016207:Cytokines; D006728:Hormones; D007328:Insulin; D005947:Glucose; D007213:Indomethacin