Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

Figures & data

Figure 1 (A) fasting blood glucose levels and (B) body weights of female diet-induced obese (DIO) C57BL/6 J mice during the 21-day dipterinyl calcium pentahydrate (DCP) dosing period. The mice were divided into four treatment groups of DCP 0, 7, 21, or 63 mg/kg/day.

Abbreviation: SEM, standard error of the mean.

Table 1 One-way analyses of variance of oral glucose (glu) tolerance test area under the curve (OGTT/AUC); plasma indoleamine 2,3-dioxygenase metabolites tryptophan (Trp), kynurenine (Kyn), and calculated Kyn/Trp ratio; and certain cytokines/chemokines

Mean ± SEM (N = 19)	DCP 0 mg/kg/day (n = 5)	DCP 7 mg/kg/day (n = 6)	DCP 21 mg/kg/day (n = 5)	DCP 63 mg/kg/day (n = 3)
OGTT/AUC mg · minute/dL*	5218 ± 905	2632† ± 517	4085 ± 600	5868 ± 831
0-minute glu (mg/dL)	170 ± 15	172 ± 20	183 ± 11	162 ± 17
30-minute glu (mg/dL)****	233 ± 11	207 ± 11	277† ± 19	312††† ± 7.8
60-minute glu (mg/dL)	200 ± 18	201 ± 17	211 ± 15	211 ± 7.5
90-minute glu (mg/dL)**	241 ± 15	178†† ± 15	163†† ± 7.7	192† ± 18
120-minute glu (mg/dL)	162 ± 13	159 ± 12	162 ± 6.3	183 ± 15
Trp (μM)	110 ± 14	110 ± 9.0	119 ± 12	122 ± 5.0
Kyn (μM)**	0.90 ± 0.14	0.96 ± 0.10	1.00 ± 0.19	1.84†† ± 0.25
Kyn/Trp (μM/mM)*	8.34 ± 1.0	8.92 ± 0.87	8.52 ± 1.3	15.13† ± 2.0
GM-CSF (pg/mL)	<160	<160	<160	192 ± 32
IFNγ (pg/mL)	<6.4	<6.4	<6.4	15.7 ± 9.3
IL-1α (pg/mL)	467 ± 258 (4)	496 ± 170	329 ± 225	348 ± 197
IL-1β (pg/mL)	34.7 ± 2.7 (4)	<32.0	41.6 ± 8.5	36.7 ± 4.7
IL-4 (pg/mL)	7.76 ± 1.4	<6.4	8.34 ± 1.9	<6.4
IL-6 (pg/mL)	59.2 ± 8.8 (4)	24.7 ± 9.6	43.2 ± 8.2 (4)	56.2 ± 36.6
IL-10 (pg/mL)	<32.0	49.0 ± 17.0	32.8 ± 0.76	<32.0
IL-12(p40) (pg/mL)	32.5 ± 0.52 (4)	<32.0	<32.0 (4)	<32.0
IL-12(p70) (pg/mL)	69.0 ± 31.5	37.8 ± 5.8	123.6 ± 80.5	72.9 ± 23.8
IL-13 (pg/mL)	197 ± 23.1	<160	<160	765 ± 604.7
MCP-1 (pg/mL)	70.8 ± 26.1	46.0 ± 14.0	49.6 ± 13.3	60.3 ± 22.2
RANTES (pg/mL)	36.6 ± 3.0 (4)	46.6 ± 13.0	33.1 ± 1.1 (3)	49.5 ± 17.5
TNFα (pg/mL)	12.0 ± 5.3	8.0 ± 1.6	10.2 ± 2.4	9.5 ± 3.1

Notes:

* P < 0.05,

** P < 0.01,

*** P < 0.005,

**** P = 0.001, for all DCP dosages tested;

† P < 0.05,

†† P < 0.01,

††† P < 0.005, for contrast tests versus 0 mg/kg/day. When actual cell numbers are different these are given in parentheses.

Abbreviations: DCP, dipterinyl calcium pentahydrate; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; IL-1α, interleukin-1 alpha; IL-1β, interleukin-1 beta; IFNγ, interferon gamma; MCP-1, monocyte chemoattractant protein-1; RANTES, regulated on activation, normal T cell expressed and secreted; SEM, standard error of the mean; TNFα, tumor necrosis factor alpha.

Table 2 Multivariate linear regression of oral glucose tolerance test area under the curve (OGTT/AUC) Coefficientsa

Model	Unstandardized coefficients		Standardized coefficients	t-statistic	P-value
	B	SE	Beta
(Constant)	1935.382	1717.742	NA	1.127	0.279
DCP^3	0.009	0.003	17.143	2.650	0.019
DCP^2	31.178	11.113	23.797	2.806	0.014
DCP	−574.513	190.252	−6.604	−3.020	0.009
Trp	29.828	14.533	0.369	2.052	0.059

Notes:

a Dependent variable is OGTT/AUC. Trp, Kyn, Kyn/Trp, granulocyte-macrophage colony-stimulating factor, interferon gamma, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-10, IL-12(p40), IL-12(p70), IL-13, monocyte chemoattractant protein-1, RANTES, and tumor necrosis factor alpha were tested by stepwise regression as predictors of OGTT/AUC. The selected variables were DCP³, DCP², DCP, and Trp (μM), where DCP is dosage (mg/kg/day); P = 0.013, R³= 0.571 for the regression OGTT/AUC = 0.009 DCP³ + 31.178 DCP² – 574.513 DCP + 29.828 Trp + 1935.382.

Abbreviations: DCP, dipterinyl calcium pentahydrate; Kyn, kynurenine; NA, not applicable; RANTES, regulated on activation, normal T cell expressed and secreted; SE, standard error; Trp, tryptophan.