Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

Fuad Lechin¹, Bertha van der Dijs¹, Betty Pardey-Maldonado¹, Jairo E Rivera¹, Marcel E Lechin², Scarlet Baez¹

¹Department of Physiological Sciences, Sections of Neuroendocrinology, Neuropharmacology, and Neurochemistry, Instituto de Medicina Experimental, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela; ²Department of Internal Medicine, Texas A & M Health Science Center, College of Medicine, TX, USA

Objective: The purpose of the trial was to examine the effects of amantadine, a N-methyl-D-aspartate (NMDA) antagonist, on the oral glucose tolerance test (OGTT) plus insulin, glucagon and neurotransmitters circulating levels. Previous findings showed that hyperinsulinism and type 2 diabetes are positively associated with neural sympathetic and adrenal sympathetic activities, respectively. These peripheral sympathetic branches depend on the pontine (A₅-noradrenergic) and the rostral ventrolateral (C₁-adrenergic) medullary nuclei. They are excited by glutamate axons which act at NMDA postsynaptic receptors.

Research design and methods: One OGTT plus placebo and one OGTT plus oral amantadine test were carried out two weeks apart in 15 caucasic normal voluntary humans. Noradrenaline, adrenaline, dopamine, plasma-free serotonin, platelet serotonin, glucose, glucagon, and insulin were measured throughout the 180-minute testing period.

Results: Maximal reductions of plasma glucose and glucagon plus exacerbated insulin rises were significantly greater throughout the oral glucose plus amantadine test than those registered throughout the oral glucose plus placebo challenge. The above findings were paralleled by greater than normal noradrenaline/adrenaline plasma ratio increases. In addition, maximal reductions of the platelet serotonin and plasma serotonin circulating values contrasted with the normal rises of these parameters, always registered during the glucose load plus placebo challenge.

Conclusion: This study supports the theory that amantadine might be a powerful antidiabetic tool and could be added to the therapeutic arsenal against type 2 diabetes.

Keywords: glucagon, insulin, type 2 diabetes, sympathetic nervous system, blood serotonin, blood catecholamines, amantadine