title: Aminophylline stimulates insulin secretion in patients with type 2 diabetes mellitus.
abstract: In healthy subjects, paracrine factors partly regulate insulin secretion and basal endogenous glucose production. Administration of pentoxifylline, an adenosine receptor antagonist, inhibits transiently endogenous glucose production in healthy humans without any changes in glucoregulatory hormone concentrations. To evaluate the modulatory role of adenosine on endogenous glucose production and basal insulin secretion in type 2 diabetes, aminophylline, a potent adenosine receptor antagonist, was administered intravenously to 5 patients with type 2 diabetes mellitus in a saline-controlled study. Endogenous glucose production was measured before and during 6 hours after administration of aminophylline/saline by primed, continuous infusion of [6,6-(2)H(2)]glucose. During both experiments, the decrease in plasma glucose concentration was similar (16% v 18% from basal, not significant [NS]). After aminophylline administration, basal endogenous glucose production was transiently inhibited within 15 minutes to 70% from basal, whereas it did not change significantly in the control experiment (P =.02). The inhibition of glucose production coincided with stimulation of insulin secretion to 144% from basal 90 minutes after the administration of aminophylline (P =.008). In the control experiment insulin secretion decreased gradually by 29% during 6 hours. We conclude that aminophylline inhibits endogenous glucose production in type 2 diabetes by stimulation of insulin secretion. Paracrine factors, such as adenosine, may be involved in the regulation of basal insulin secretion in type 2 diabetes mellitus.
authors.affiliation: Metabolism Unit, Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Arias
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: G
authors.initials: G
authors.lastname: Nijpels
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: H P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000368:Aged; D000628:Aminophylline / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D058915:Purinergic P1 Receptor Antagonists
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D058915:Purinergic P1 Receptor Antagonists; D000628:Aminophylline; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine