Influence of verapamil on human glucose tolerance

doi:10.1016/0002-9149(86)90804-0

The American Journal of Cardiology

Volume 57, Issue 7, 26 February 1986, Pages D39-D43

https://doi.org/10.1016/0002-9149(86)90804-0 Get rights and content

Abstract

Studies have indicated that verapamil inhibits insulin release from pancreatic β cells in vitro. Studies in this clinic, however, showed that both oral pretreatment with verapamil for 1 week and intravenous infusion of the drug over a period of 3 hours improved oral glucose tolerance in patients with type II diabetes without affecting insulin release. In contrast, verapamil failed to increase further the hypoglycemic effect of oral glibenclamide therapy when administered intravenously in diabetic patients. This hypoglycemic effect of verapamil does not appear to be caused by reduced glucose absorption from the gut because intravenous infusion of verapamil left the portal vein glucose response to glucose ingestion unaffected in normoglycemic patients who underwent portal vein catheterization for diagnostic purposes. It is more likely that verapamil affects the liver, leading to decreased hepatic glucose output, which supports previous reports that have shown an inhibitory influence of verapamil on enzymes involved in the gluconeogenetic and glycogenolytic processes.

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The open trial was designed to evaluate the effects of long-term antihypertensive treatment with the calcium-channel blocker, manidipine and the angiotensin converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients with essential hypertension. We measured the insulin sensitivity index (S_I) and the glucose-effectiveness (S_G) by the use of Bergman's minimal model method in 18 hypertensive NIDDM patients before and after administration of manidipine (group A) or delapril (group B) for 3 months. Manidipine treatment for 3 months significantly improved S_I in group A from 3.35 ± 0.61 (× 10⁻⁴ min⁻¹ μU⁻¹ ml⁻¹) to 4.70 ± 1.34 (P < 0.05). Delapril treatment for 3 months also significantly improved S_I in group B from 3.56 ± 1.04 to 5.00 ± 0.87 (P < 0.05). Manidipine significantly improved S_G in group A from 1.60 ± 0.64 (× 10⁻² min) to 2.19 ± 0.38 (P < 0.05). Delapril treatment also significantly improved S_G in the group B from 1.41 ± 0.56 to 1.91 ± 0.35 (P < 0.05). Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in the hypertensive NIDDM patients. Treatment with manidipine or delapril significantly reduced systolic and diastolic blood pressures in the hypertensive NIDDM patients. There were no differences between plasma glucose, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate and body weight after 3 months on manidipine or delapril. This study confirmed the improving effects on S_I and S_G by long-term treatment with manidipine or delapril in the hypertensive NIDDM patients.
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Influence of verapamil on human glucose tolerance

Abstract

J Biol Chem

Metabolism

Biochem Pharmacol

Metabolism

Insulin secretion: multifactorial regulation for a single process of release

Diabetologia

The stimulus-secretion coupling of glucose-induced insulin release. V. The participation of a microtubular-microfilamentous system

Diabetes

Mechanisms involved in α-adrenergic phenomena: role of calcium ions in actions of catecholamines in liver and other tissues

Am J Physiol

Inhibition by calcium channel blockers of the glycogenolytic effect of glucogon in perfused rat liver

Acta Endocrinol (Copenh)

Effects of Ca ions on membranes

Hyperglycemic effect of nifedipine

Br Med J

Effect of nifedipine on glucose tolerance and insulin secretion in diabetic and non-diabetic patients

Curr Med Res Opin

Impairment of insulin secretion in man by nifedipine

Eur J Pharmacol

Influence de nifedipine, antagoniste du calcium, sur l'utilisation du glucose

Rev Med Therap

Hypercalcemic and calcium-antagonistic effects on insulin release and oral glucose tolerance in man

Acta Med Scand

The interference of orally given verapamil as an anti-hypertensive agent on the glucose-induced insulin release in 20 normoglycemic patients with mild arterial hypertension

The influence of orally given verapamil as an anti-hypertensive agent on the glucose-induced insulin release in 10 mildly hypertensive patients with impaired glucose tolerance

Critical variables in the radioimmunoassay of serum insulin using the double antibody technic

Diabetes