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

Figures & data

Table 1 Correlations found during the oral glucose tolerance + placebo test performed in 15 normal voluntary human (seven males and eight females)

	Periods
	0 min	30 min	60 min	90 min	120 min	180 min
NA vs Ad	ns	ns	ns	ns	ns	ns
NA vs DA	ns	ns	0.203*	0.256*	0.321**	0.293**
Ad vs DA	ns	ns	ns	ns	ns	ns
NA vs glycemia	ns	ns	−0.221*	−0.325**	−0.442**	−0.456**
DA vs glycemia	ns	ns	−0.211*	−0.247*	−0.354**	−0.376**
Ad vs glycemia	ns	ns	ns	ns	ns	ns
NA vs p5-HT	ns	ns	ns	ns	ns	ns
Ad vs p5-HT	ns	ns	ns	ns	ns	ns
DA vs p5-HT	ns	ns	ns	ns	ns	ns
p5-HT vs glycemia	ns	ns	ns	ns	ns	ns
NA vs insulin	ns	ns	0.325*	0.411**	0.401**	0.397**
DA vs insulin	ns	ns	0.214*	0.222*	0.216*	0.217*
Ad vs insulin	ns	ns	ns	ns	ns	ns
p5-HT vs insulin	ns	ns	−0.212*	−0.223	−0.231*	−0.214*
NA vs glucagon	ns	ns	−0.299*	−0.297*	−0.365**	−0.377**
DA vs glucagon	ns	ns	ns	−0.288*	−0.322*	−0.315*
Ad vs glucagon	ns	ns	ns	ns	ns	ns
P5-HT vs glucagon	ns	ns	ns	ns	ns	ns
NA vs HR	ns	ns	ns	ns	ns	ns
Ad vs HR	ns	ns	ns	ns	ns	ns
DA vs HR	ns	ns	ns	ns	ns	ns
NA/Ad vs SBP	ns	ns	ns	ns	ns	ns
NA/Ad vs DBP	ns	ns	0.207*	0.214*	0.221*	0.218*
DA vs SBP	ns	ns	ns	ns	ns	ns
DA vs DBP	ns	ns	−0.213*	−0.210*	−0.220*	−0.222*

Notes: Levels of significance,

* P < 0.05;

** P < 0.01.

Abbreviations: NA, noradrenaline; Ad, adrenaline; DA, dopamine; p5-HT, platelet serotonin; f5-HT, plasma serotonin; HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Table 2 Correlations found during the oral glucose tolerance + amantadine test performed in 15 normal voluntary human (seven males and eight females)

	Periods
	0 min	30 min	60 min	90 min	120 min	180 min
NA vs Ad	ns	ns	ns	ns	ns	ns
NA vs DA	ns	ns	0.368**	0.377**	0.405**	0.426**
Ad vs DA	ns	ns	ns	ns	ns	ns
NA vs glycemia	ns	ns	−0.267*	−0.338**	−0.422**	−0.439**
DA vs glycemia	ns	ns	−0.332*	−0.365*	−0.411**	−0.395**
Ad vs glycemia	ns	ns	ns	ns	ns	ns
NA vs p5-HT	ns	ns	−0.244*	−0.332*	−0.326*	−0.299*
Ad vs p5-HT	ns	ns	ns	ns	ns	ns
DA vs p5-HT	ns	ns	−0.237*	−0.314*	−0.333*	ns
p5–HT vs glycemia	ns	ns	0.244*	0.338*	0.352*	0.341*
NA vs insulin	ns	ns	0.211*	0.253*	0.324**	0.323**
DA vs insulin	ns	ns	0.199*	0.218*	0.235*	0.239*
Ad vs insulin	ns	ns	ns	ns	ns	ns
p5-HT vs insulin	ns	ns	−0.368**	−0.387**	−0.359**	−0.371**
NA vs glucagon	ns	ns	−0.318*	−0.409**	−0.396**	−0.402**
DA vs glucagon	ns	ns	−0.297*	−0.346*	−0.401**	−0.411**
Ad vs glucagon	ns	ns	ns	ns	ns	ns
P5-HT vs glucagon	ns	ns	ns	0.363*	0.402**	0.416**
NA vs HR	ns	ns	ns	ns	ns	ns
Ad vs HR	ns	ns	ns	ns	ns	ns
DA vs HR	ns	ns	ns	ns	ns	ns
NA/Ad vs SBP	ns	ns	ns	ns	ns	ns
NA/Ad vs DBP	ns	ns	0.232*	0.229*	0.239*	0.241*
DA vs SBP	ns	ns	ns	ns	ns	ns
DA vs DBP	ns	ns	−0.218*	−0.222*	−0.219*	−0.231*

Notes: Levels of significance,

* P < 0.05;

** P < 0.01.

Abbreviations: NA, noradrenaline; Ad, adrenaline; DA, dopamine; p5-HT, platelet serotonin; f5-HT, plasma serotonin; HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Table 3 Changes in SBP, DBP, and HR induced in 15 normal voluntary healthy humans (eight males and seven females) when one OGTT plus placebo and one OGTT plus amantadine tests were carried out two weeks apart

	OGTT + placebo test		OGTT + amantadine test
	0 min	180 min	0 min	180 min
HR (beats/min)	71 ± 5	66 ± 7*	73 ± 7	65 ± 8**
SBP (mm Hg)	127 ± 8	122 ± 3	127 ± 8	124 ± 7
DBP (mm Hg)	73 ± 5	76 ± 4*	71 ± 6	88 ± 4**

Notes: Results are expressed as mean ± SEM.

* P < 0.05;

** P < 0.01 (versus 0 min value).

Abbreviations: DBP, diastolic blood pressure; HR, heart rate; OGTT, oral glucose tolerance test; SBP, systolic blood pressure; SEM, standard error of mean.

Figure 1 The addition of an oral dose of amantadine (100 mg) to an oral glucose load potentiated both the glucose and glucagon reductions and increased postprandial insulin levels in 15 normal healthy subjects (seven males and eight females), whose ages ranged from 25 to 58 years (mean ± SEM = 38.4 ± 7.2).

Notes: Values are expressed as mean ± SEM *P < 0.05; **P < 0.02 (versus 0 min value).
Abbreviation: SEM, standard error of mean.

Figure 2 The addition of an oral dose of amantadine (100 mg) to an oral glucose load enhanced the normal noradrenaline and dopamine rises, always observed throughout the OGTT + placebo test. Conversely, maximal reduction of adrenaline opposed the former rises.

Notes: N = 15 (seven males and eight females), whose ages ranged from 25 to 58 years (mean ± SEM = 38.4 ± 7.2). Values are expressed as mean ± SEM. *P < 0.05; **P < 0.02; ***P < 0.01 (versus 0 min value).
Abbreviations: OGTT, oral glucose tolerance test; SEM, standard error of mean.

Figure 3 The insulin/glucagon ratio as well as the noradrenaline/adrenaline ratio showed paralleled increases throughout the oral glucose tolerance test when 100 mg of oral amantadine was given to 15 normal healthy subjects (seven males and eight females), whose ages ranged from 25 to 58 years (mean ± SEM = 38.4 ± 7.2).

Notes: Values are expressed as mean ± SEM. *P < 0.05; **P < 0.02 (versus 0 min value).
Abbreviation: SEM, standard error of mean.

Figure 4 Both platelet serotonin (p5-HT) and plasma serotonin (f5-HT) showed maximal decreases throughout the test when an oral dose of amantadine (100 mg) was added to an oral glucose load. These findings contrast with the significant rises of both parameters observed throughout the oral glucose load + placebo challenge.

Notes: N = 15 (seven males and eight females), whose ages ranged from 25 to 58 years (mean ± SEM = 38.4 ± 7.2). Values are expressed as mean ± SEM. *P < 0.05; ***P < 0.01 (versus 0 min value).
Abbreviation: SEM, standard error of mean.