Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in db/db diabetic mice

doi:10.4239/wjd.v11.i12.596

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 11, Issue 12

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (6850)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Figures (1-6) series, Tables (1-5) series.

Item

Count

PDF

490

WORD

168

HTML

2961

Figures (1-6)

236

Tables (1-5)

202

Sum=4057

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

281

Download

756

Sum=1037

Publishing Process of This Article

Item

Count

Browse

521

Download

1235

Sum=1756

Dec 15, 2020 (publication date) through Apr 19, 2024

Times Cited of This Article

Times Cited (16)

Journal Information of This Article

Publication Name

World Journal of Diabetes

ISSN

1948-9358

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Diabetes. Dec 15, 2020; 11(12): 596-610
Published online Dec 15, 2020. doi: 10.4239/wjd.v11.i12.596

Table 1 Body weight and fat mass in db/db and db/+ mice

Parameter	Age in wk	Group
		*Non-diabetic db/+* mice (n = 9)**	*db/db* diabetic mice
		*Non-diabetic db/+* mice (n = 9)**	Vehicle (n = 10)	EMPA (n = 9)
Body weight (g)	8	26.8 (25.0-31.1)	37.1 (32.1–41.6)^b	37.4 (28.5–41.5)^b
	12	26.2 (23.5–28.2)	37.5 (35.8–40.5)^b	46.2 (38.8–53.0)^b^,^c
	16	24.8 (21.6–27.7)^e	37.8 (34.3–40.4)^b	52.6 (42.5–62.2)^b^,^c^,^f
Fat mass (g)	8	3.1 (1.9–4.1)	18.3 (16.2–22.5)^a	18.4 (13.5–20.6)^b
	12	2.7 (1.9–3.3)	19.5 (17.0–22.7)^b	25.3 (21.7–30.9)^b^,^c
	16	2.7 (2.1–4.5)	19.6 (17.4–22.7)^b	28.0 (22.2–35.3)^a^,^d^,^e
Fat mass (%)	8	11.4 (8.5–16.1)	50.6 (46.6–55.3)^b	49.3 (46.8–50.0)^b
	12	10.7 (8.1–12.4)	52.5 (45.2–57.0)^b	55.5 (51.5–58.3)^b
	16	11.7 (7.6–13.2)	55.0 (42.5–62.8)^b	53.4 (49.1–56.7)^b

^aP< 0.01 vs non–diabetic control (db/+ mice, Mann-Whitney U-test).

^bP< 0.001 vs non–diabetic control (db/+ mice, Mann-Whitney U-test).

^cP< 0.01 vs placebo (Mann-Whitney U-test).

^dP< 0.001 vs placebo (Mann-Whitney U-test).

^eP< 0.01 vs wk 8 and 12 (ANOVA-χ² test).

^fP < 0.001 vs wk 8 and 12 (ANOVA-χ² test). Data are presented as medians (min–max values). EMPA: Empagliflozin.

Table 2 Plasma biochemistry in db/+ and db/db mice

Parameter	Age in wk	Group
		*Non-diabetic db/+* mice (n = 9)**	*Diabetic db/db* mice**
		*Non-diabetic db/+* mice (n = 9)**	Vehicle (n = 10)	EMPA (n = 9)
Glucose (mmoL/L)	8	9.50 (5.10–11.4)	28.5 (16.8–40.1)^b	23.1 (15.3–35.4)^b
	12	9.20 (6.10–9.50)	30.4 (22.7–48.0)^b	16.3 (13.6–20.7)^b^,^d^,^e
	16	9.50 (8.50–12.2)	32.7 (22.5–53.1)^b	16.1 (9.9–23.6)^b^,^d^,^e
Fructosamine (µmoL/L)	8	237 (217–249)	456 (424–511)^b	480 (425–579)^b
Fructosamine (µmoL/L)	16	239 (222–296)	622 (524–672)^b^,^f	468 (341–491)^b^,^c^,^e
Glycated albumin (µmoL/L)	8	107 (103–127)	227 (206–239)^b	235 (217–261)^b
Glycated albumin (µmoL/L)	16	117 (109–133)	283 (252–349)^b^,^f	210 (166–245)^b^,^c^,^e
Total cholesterol (mmoL/L)	8	2.76 (1.80–3.96)	2.72 (1.48–4.86)	2.76 (1.60–4.05)
Total cholesterol (mmoL/L)	16	2.37 (1.98–2.97)	3.57 (1.68–4.86)^e	4.05 (2.10–5.22)^e
HDL-cholesterol (mmoL/L)	8	1.17 (0.50–1.62)	1.20 (0.51–2.01)	1.40 (0.93–1.89)
HDL-cholesterol (mmoL/L)	16	1.26 (0.45–1.80)	1.50 (0.48–2.19)	2.31 (1.05–2.88)^e
LDL-cholesterol (mmoL/L)	8	1.32 (0.81–2.10)	1.02 (0.84–2.72)	1.07 (0.84–2.60)
LDL-cholesterol (mmoL/L)	16	0.81(0.75–1.11)^f	0.81 (0.72–1.14)	1.05 (0.60–1.41)
Triglycerides (mmoL/L)	8	1.74 (0.90–2.70)	1.14 (0.51–2.30)	1.25 (0.87–2.30)
Triglycerides (mmoL/L)	16	1.35 (0.81–2.58)	1.79 (1.17–3.54)^e	1.77 (1.29–3.87)^e
Creatinine (µmoL/L)	8	67.0 (47.0–78.0)	76.4 (70.2–84.2)	70.5 (54.0–82.2)
	12	68.6 (48.5–74.5)	76.5 (64.5–100.5)^a	74.7 (46.2–85.8)^a
	16	61.8 (54.0–71.7)	75.6 (63.9–89.4)^a	81.3 (55.8–91.2)^a
Uric acid (µmoL/L)	8	273 (104–420)	173 (143–341)	281 (165–507)
Uric acid (µmoL/L)	16	235 (159–271)	170 (143–187)	204 (179-242)

^aP < 0.01 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^bP < 0.001 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^cP < 0.01 vs placebo db/db group (Mann-Whitney U-test).

^dP < 0.001 vs placebo db/db group (Mann-Whitney U-test).

^eP < 0.05 vs placebo db/db group (Mann-Whitney U-test).

^fP < 0.01 compared with wk 8 (Wilcoxon test). Data are presented as medians (min–max values). EMPA: Empagliflozin.

Table 3 Plasma levels of leptin and insulin in db/+ and db/db mice

Hormone	Age in wk	Group
		*Non-diabetic db/+* mice (n = 9)**	*Diabetic db/db* mice**
		*Non-diabetic db/+* mice (n = 9)**	Vehicle (n = 10)	EMPA (n = 9)
Leptin (ng/mL)	8	3.3 (1.4–6.54)	97.1 (53.2–114.4)^b	93.4 (80.8–133.1)^b
Leptin (ng/mL)	16	3.8 (1.5–6.3)	90.0 (21.2–151.4)^b	136.4 (53.0–171.2)^b^,^c^,^d
Insulin (ng/mL)	8	5.6 (3.4–18.0)	25.6 (11.5–45.2)^b	21.2 (10.8–40.8)^b
Insulin (ng/mL)	16	10.0 (2.1–22.2)	22.1 (9.8–33.2)^a	20.8 (6.0–56.7)^a
Glucagon (ng/mL)	8	370 (250–2670)	660 (190–2760)	450 (290–2180)
Glucagon (ng/mL)	16	370 (150–2120)	605 (260–2960)	390 (240–860)

^aP < 0.01 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^bP < 0.001 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^cP < 0.05 vs placebo (Mann-Whitney U-test).

^dP < 0.05 vs wk 8 (Wilcoxon test). Data are presented as medians (min–max values). EMPA: Empagliflozin.

Table 4 Renal structural parameters in db/+ and db/db mice

Parameter	Group
	*Non-diabetic db/+* mice (n = 9)**	*Diabetic db/db* mice**
	*Non-diabetic db/+* mice (n = 9)**	Vehicle (n = 10)	EMPA (n = 9)
Mesangium, fractional volume (%)	14.4 (9.8–18.5)	38.6 (34.5–42.7)^a	25.5 (20.4–35.8)^d
Capillaries, fractional volume (%)	31.3 (28.9–38.7)	34.6 (30.9–36.1)	33.3 (29.5–37.0)
GBM, mean width (nm)	135 (116–157)	163 (135–203)^a	139 (116–225)^b
Podocyte FPs, mean width (nm)	220 (191–242)	372 (299–426)^a	203 (162–317)^c
Podocyte FPs (N_A, nm^–1)	3.39 (3.00–3.79)	2.73 (1.92–3.51)^a	3.31 (2.32–4.18)^b

^aP < 0.01 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^bP < 0.05 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^cP < 0.01 vs non-diabetic control (db/+ mice, Mann-Whitney U-test).

^dP < 0.001 vs placebo (Mann-Whitney U-test). Data are presented as medians (min–max values). GBM: Glomerular basement membrane; FPs: Foot processes; EMPA: Empagliflozin.

Table 5 The relationships of glycemic control indicators, plasma creatinine and urinary albumin-to-creatinine ratio with renal structural parameters

Parameter	Fructosamine	Glycated albumin	Plasma creatinine	UACR
Mesangial volume, V_V	r = 0.69	r = 0.67	r = 0.57	r =0.81
Mesangial volume, V_V	P = 0.0002	P = 0.0004	P = 0.004	P = 0.000002
Capillary volume, V_V	r = 0.13	r = 0.11	r = 0.30	r = 0.05
Capillary volume, V_V	P > 0.05	P > 0.05	P > 0.05	P > 0.05
GBM width	r = 0.69	r = 0.69	r = 0.21	r = 0.53
GBM width	P = 0.0008	P = 0.007	P > 0.05	P = 0.02
Podocyte FPs, width	r = 0.62	r = 0.63	r = –0.15	r = 0.50
Podocyte FPs, width	P = 0.003	P = 0.003	P > 0.05	P = 0.03
Podocyte FPs, N_A	r = –0.57	r = -0.58	r = 0.04	r = –0.25
Podocyte FPs, N_A	P = 0.008	P = 0.007	P > 0.05	P > 0.05
Nephrin-positive areas in glomeruli, V_V	r = –0.68	r = –0.65	r = –0.51	r = –0.76
Nephrin-positive areas in glomeruli, V_V	P = 0.006	P = 0.009	P = 0.04	P = 0.001
TGF-β positive areas in glomeruli, V_V	r = 0.65	r = 0.65	r = 0.09	r = 0.67
TGF-β positive areas in glomeruli, V_V	P = 0.003	P = 0.002	P >0.05	P = 0.001

UACR: Urinary albumin-to-creatinine ratio; GBM: Glomerular basement membrane; FPs: Foot processes; Vv: Volumetric density; TGF-β: Transforming growth factor β. Spearman’s rank correlation coefficients are shown.

Citation: Klimontov VV, Korbut AI, Taskaeva IS, Bgatova NP, Dashkin MV, Orlov NB, Khotskina AS, Zavyalov EL, Klein T. Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in db/db diabetic mice. World J Diabetes 2020; 11(12): 596-610
URL: https://www.wjgnet.com/1948-9358/full/v11/i12/596.htm
DOI: https://dx.doi.org/10.4239/wjd.v11.i12.596