Adenosine triphosphate-sensitive potassium channels are involved in insulin-mediated glucose transport in humans.
We investigated the influence of treatment with nicorandil, a K-channel opener currently used for angina, on glucose homeostasis in patients with non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Adenosine triphosphate (ATP)-sensitive K (K-ATP) channels are present in various tissues, including pancreatic B cells and skeletal muscle, and are the putative targets of this agent. Nine NIDDM patients with CAD and five healthy subjects participated in the study. Fasting plasma levels (mean+/-SEM) of glucose (144+/-11 to 180+/-22 mg/dL, P<.05) and insulin (5.8+/-1.6 to 7.0+/-1.8 microU/mL, P<.05) and hemoglobin A1c (7.54+/-0.47 to 8.11+/-0.55%, P<.01) increased significantly in nine NIDDM patients after treatment with nicorandil at a dose of 5 mg three times daily for 2 to 8 months. Glucose tolerance as examined by an identical meal test deteriorated (P<.001), but the insulin response did not change significantly. A washout of nicorandil for 1 to 4 months restored glucose tolerance almost to pretreatment levels in four patients. A 5- to 7-day trial of nicorandil (5 mg three times daily) in five healthy subjects resulted in a marginal to twofold increase in fasting plasma insulin, reflecting the progression of insulin resistance. In addition, three healthy subjects showed a substantial reduction in the glucose infusion rate (GIR) required in the euglycemic-hyperinsulinemic clamp study. Since the therapeutic dose of nicorandil did not affect pancreatic B-cell function but caused insulin resistance in both healthy and NIDDM subjects, we conclude that K-ATP channels play a regulatory role in insulin-mediated glucose transport in humans.
Wasada
T
T
Diabetes Center, Tokyo Women's Medical University, School of Medicine, Japan.
Watanabe
C
C
Nakagami
T
T
Iwamoto
Y
Y
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000502:physiology*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D054086:KATP Channels; D008297:Male; D008875:Middle Aged; D020108:Nicorandil / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D054086:KATP Channels; D020108:Nicorandil; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel