DIBc, a nanochelating-based nano metal-organic framework, shows anti-diabetic effects in high-fat diet and streptozotocin-induced diabetic rats

Figures & data

Table 1 BET test results on DIBc NMOF

Material	Ligand	BET value (m^2/g)
DIBc	Pendant carboxylate	4460

Abbreviation: NMOF, nano metal–organic framework.

Table 2 Groups of rats and their regimen

	Group name	High-fat diet	STZ	Medications
Controls	A (normal control)	−	−	–
	B (high-fat control)	+	−	–
	C (diabetic control)	+	+	–
Treatments	D (DIBc low dose)	+	+	0.4 µg/kg/day DIBc (i.p)
	E (DIBc medium dose)	+	+	4 µg/kg/day DIBc (i.p)
	F (DIBc high dose)	+	+	40 µg/kg/day DIBc (i.p)
	G (metformin)	+	+	80 mg/kg/day metformin (orally)

Abbreviations: i.p, intraperitoneally; STZ, streptozotocin.

Table 3 Composition of normal and high-fat diet

	Control		High-fat diet
	g%	kcal%	g%	kcal%
Protein	17.5	18.48	11.38	8.11
Carbohydrate	72.72	76.77	47.27	33.69
Soybean oil	2	4.75	1.3	2.08
Butter	–	–	35	56.12
Fiber	6.6	0	4.29	0
Total phosphate	0.42	0	0.28	0
Total calcium	0.56	0	0.37	0
Other minerals	0.1	0	0.6	0
Vitamins	0.1	0	0.6	0
Caloric density (kcal/g)	3.8		5.8

Figure 1 The timeline of study.

Abbreviation: STZ, streptozotocin.

Figure 2 HRTEM image of DIBc NMOF, which indicates that the size of the NMOF is about 25–30 nm.

Abbreviations: HRTEM, high-resolution transmission electron microscopy; NMOF, nano metal–organic framework.

Table 4 DIBc effects on food and water intake and weight gain

Group	Week of study	Normal control	High-fat group	Diabetic control	DIBc low dose	DIBc medium dose	DIBc high dose	Metformin
Weight gain (g)	11	29.6±6	41.7±5.2^#	−10.3±6.3^#	−14±3.1	–7±2.8	1±0.05*	–5±1.5
Food intake (g)	5	16.9±2.5	13.2±2.1^#	15.5±1.3	15±2.3	14±1.9	13.5±1.7	14.7±2.6
	8	16.2±3.25	13.6±1.86	15.7±2.9	15±1.6	13±2.5	14±2.4	15±1.8
	11	16.4±2.88	14.1±2.2	15.1±1.7	13±2.5	15±2.4	16±2.2	15.2±1.3
Water intake (mL)	5	31.5±4.3	22.1±4.5^#	54.6±10.1^#	62±7.6	58±9.6	54±8.4	68±12.5
	8	24.1±5.1	19.3±2.8^#	58.9±11.9^#	65±10.4	46±7.3	55±7.1	66±8.5
	11	25.4±4.9	19.7±3.1^#	67.8±7.3^#	48±6.5*	52±8.6	50±6.7*	55±13.8

Notes: Each number shows mean ± SEM for eight rats. Significant differences vs the normal control group have been specified by square (^#) meaning P-value <0.05. Significant differences vs the diabetic group have been specified by asterisk (*) meaning P-value <0.05.

Table 5 DIBc effects on plasma glucose, insulin, TG, cholesterol, LDL, and HDL level

Group	Week of study	Normal control	High-fat group	Diabetic control	DIBc low dose	DIBc medium dose	DIBc high dose	Metformin
Insulin (µg/L)	5	0.23±0.09	0.63±0.07^#	0.48±0.08^#	0.54±0.12	0.52±0.13	0.52±0.9	0.43±0.07
	8	0.2±0.038	0.52±0.08^#	0.37±0.09^#	0.37±0.07	0.35±0.06	0.72±0.08*	0.63±0.09*
	11	0.29±0.06	0.4±0.06^#	0.31±0.07	0.29±0.03	0.28±0.04	0.57±0.7*	0.21±0.06
Glucose (mg/dL)	5	90.5±15.2	83.2±16.2	272.3±35.9^#	344±61.8*	274±45.2	266±41.3	352±67.3*
	8	82.3±12.3	138.3±23.3^#	376.1±49.5^#	338±42.3	292±51.4*	332±50.5*	258±43.1*
	11	100.9±16.5	143.2±21.2^#	380.4±50.2^#	281±46.2*	267±39.8*	294±49.4*	404±72.8*
HOMA-IR index	5	0.051±0.02	0.13±0.03^#	0.32±0.06^#	0.45±0.03*	0.35±0.07	0.34±0.09	0.37±0.05
	8	0.04±0.01	0.17±0.02^#	0.31±0.09^#	0.3±0.06	0.25±0.09	0.59±0.08*	0.4±0.07
	11	0.072±0.03	0.14±0.04^#	0.29±0.05^#	0.2±0.03*	0.18±0.05*	0.41±0.05*	0.2±0.08
TG (mg/dL)	5	39.2±12.8	154.9±21.3^#	225.6±43.2^#	230±39.1	134±23.6*	204±31.4*	220±38.5
	8	59.5±16.3	129.1±25.2^#	180.2±33.4^#	205±33.6*	155±30.1*	200±36.2	173±31.7
	11	70.6±17.9	113.5±18.6^#	130.3±22.9^#	172±28.3*	144±19.3	215±35.5*	141±28.4
Total cholesterol (mg/dL)	5	36.6±11.1	47.3±12.3	93.6±19.2^#	102±21.3	89±13.9	96±18.7	89±15.1
	8	36.1±10.9	89.6±17.5^#	131.9±26.3^#	123±26.1	106±17.4*	121±15.9	110±19.6
	11	56.5±15.1	86.4±20.4^#	134.8±21.9^#	97±15.9*	88±9.5*	101±17.3*	141±22.7
LDL (mg/dL)	5	18.5±4	20.3±4.5	42.1±5.2^#	48±8.2	47±7.2	48±6.1	41±6.8
	8	18.4±3.5	29.4±8.23^#	50.3±9.6^#	41±6.9*	47±8.9	45±7.2	48±7.1
	11	23.6±6.5	36.7±7.2^#	55.5±8.8^#	37±4.8*	37±6.1*	40±5.9*	51±9.4
HDL (mg/dL)	5	18.3±3.5	15.6±5.2	29.1±5.4^#	35±6.4	33±5.2	36±7.6	31±6.3
	8	19.8±4.3	33.1±6.1^#	35.7±7.2^#	32±5.1	29±4.9*	33±5.4	36±8.7
	11	21.4±3.8	34.4±4.9^#	40.8±6.9^#	27±4.5*	22±5.1*	24±6.8*	42±9.6

Notes: Each number shows mean ± SEM for eight rats. Significant differences vs the normal control group have been specified by square (^#) meaning P-value <0.05. Significant differences vs the diabetic group have been specified by asterisk (*) meaning P-value <0.05.

Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; HOMA-IR, homeostasis model assessment of insulin resistance; TG, triglycerides.

Figure 3 The percentage of HOMA-IR index and plasma glucose and insulin changes in each group at week 11 compared with the fifth week of the study. Each column shows mean ± SEM for eight rats.

Abbreviation: HOMA-IR, homeostasis model assessment of insulin resistance.

Figure 4 The plasma level of TNF-α (A) and MDA (B). Each column shows mean ± SEM for eight rats.

Notes: Significant differences vs the normal control group have been specified by square (#) meaning P-value <0.05. Significant differences vs the diabetic group have been specified by asterisk (*) meaning P-value <0.05.

Abbreviation: MDA, malondialdehyde.

Figure 5 Hepatic (A) and plasma (B) iron level. Each column shows mean ± SEM for eight rats.

Note: Significant differences vs the normal control group have been specified by square (#) meaning P-value <0.05.

Figure 6 Hemoglobin concentration (A), RBC count (B), hematocrit (C) and mean cell volume (D). Each column shows mean ± SEM for eight rats.

Notes: Significant differences vs the normal control group have been specified by square (^#) meaning P-value <0.05. Significant differences vs the diabetic group have been specified by asterisk (*) meaning P-value <0.05.

Figure 7 The area of islets (A) and their numbers (B).

Notes: Each column shows mean ± SEM for eight rats. Significant differences vs the normal control group have been specified by square (#) meaning P-value <0.05. Significant differences vs the diabetic group have been specified by asterisk (*) meaning P-value <0.

Figure 8 H&E images from pancreatic islet of rats in different groups: normal control group (A), high-fat diet group (B), diabetic control group (C), DIBc low-dose group (D), DIBc medium-dose group (E), and DIBc high-dose group (F).

Figure 9 The schema of the proposed mechanism for the inhibitory effects of DIBc on diabetes.