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Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1

Luo, Xu, Li, Rong-Rong, Li, Yu-Qi, Yu, Han-Pu, Yu, Hai-Ning, Jiang, Wen-Guo, Li, Ya-Na·2022·Molecular Medicine Reports
DOI 10.3892/mmr.2022.12801PMC PMC9366154
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Figure 1. Systemic VEGFB-knockdown mouse model construction and genetic identification. (A) VEGFB gene structure, gRNA target site and deletion region. Boxes and lines respectively represent exons and introns. F1 and R1 arrows indicate the position of primers for PCR genotyping. 1–7 shows the VEGFB gene sequence, where the red line represents the VEGFB knockout gene sequence. (B-E) Western blot analysis of VEGFB protein in liver tissues and pancreas. (F and G) mRNA analysis in the liver tissues and pancreas. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 1. Systemic VEGFB-knockdown mouse model construction and genetic identification. (A) VEGFB gene structure, gRNA target site and deletion region. Boxes and lines respectively represent exons and introns. F1 and R1 arrows indicate the position of primers for PCR genotyping. 1–7 shows the VEGFB gene sequence, where the red line represents the VEGFB knockout gene sequence. (B-E) Western blot analysis of VEGFB protein in liver tissues and pancreas. (F and G) mRNA analysis in the liver tissues and pancreas. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 2. Effect of VEGFB downregulation on liver and pancreas. (A) Body weight curve of mice (4–32 weeks). (B) Food intake curve of mice (4–32 weeks) (C and D) Organ coefficient ratio between liver and pancreas in mice. (E) Light microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 50 µm; magnification, ×400). (F) Electron microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 1 µm; images a and c, ×15,000 magnification; images b and d, ×8,000 magnification). (G and H) Density of mature and immature vesicles. ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 2. Effect of VEGFB downregulation on liver and pancreas. (A) Body weight curve of mice (4–32 weeks). (B) Food intake curve of mice (4–32 weeks) (C and D) Organ coefficient ratio between liver and pancreas in mice. (E) Light microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 50 µm; magnification, ×400). (F) Electron microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 1 µm; images a and c, ×15,000 magnification; images b and d, ×8,000 magnification). (G and H) Density of mature and immature vesicles. ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 3. Effect of VEGFB downregulation on serum glucose and lipid metabolism. (A) Total cholesterol. (B) Triglycerides. (C) Low density lipoprotein-cholesterol (D) High density lipoprotein-cholesterol. (E) Fasting blood glucose. (F) Postprandial blood glucose. (G) HbA1c. (H) Serum glucose level. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 3. Effect of VEGFB downregulation on serum glucose and lipid metabolism. (A) Total cholesterol. (B) Triglycerides. (C) Low density lipoprotein-cholesterol (D) High density lipoprotein-cholesterol. (E) Fasting blood glucose. (F) Postprandial blood glucose. (G) HbA1c. (H) Serum glucose level. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 4. Effect of VEGFB downregulation on blood glucose balance and insulin resistance. (A) OGTT. (B) Area under the curve in OGTT. (C) IPITT. (D) Area under the curve in IPTT. (E) Fasting insulin. (F) Serum glucagon. (G) HOMA-IR. (H) HOMA-β. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. HOMA-IR, insulin resistance index; HOMA-β, pancreatic β-cell secretion index. VEGFB, vascular endothelial growth factor B.
Figure 4. Effect of VEGFB downregulation on blood glucose balance and insulin resistance. (A) OGTT. (B) Area under the curve in OGTT. (C) IPITT. (D) Area under the curve in IPTT. (E) Fasting insulin. (F) Serum glucagon. (G) HOMA-IR. (H) HOMA-β. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. HOMA-IR, insulin resistance index; HOMA-β, pancreatic β-cell secretion index. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 5. Expression of VEGFR1 and NRP1 in the liver and islets after VEGFB downregulation. (A) Dithizone staining to identify islet cells (magnification, ×400). (B) Numbers of islets. (C-H) Western blot analysis of VEGFB and NRP1 protein in liver tissues and islets. (I-L) mRNA analysis of VEGFB and NRP1 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B; NRP1, neuropilin-1.
Figure 5. Expression of VEGFR1 and NRP1 in the liver and islets after VEGFB downregulation. (A) Dithizone staining to identify islet cells (magnification, ×400). (B) Numbers of islets. (C-H) Western blot analysis of VEGFB and NRP1 protein in liver tissues and islets. (I-L) mRNA analysis of VEGFB and NRP1 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B; NRP1, neuropilin-1.CC BY-NC-ND · PubMed Central
Figure 6. Expression of VEGFA and VEGFR2 in the liver and islets after VEGFB downregulation. (A-F) Western blot analysis of VEGFA and VEGFR2 protein in liver tissues and islets. (B) Numbers of islets. (G-J) mRNA analysis of VEGFA and VEGFR2 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group.
Figure 6. Expression of VEGFA and VEGFR2 in the liver and islets after VEGFB downregulation. (A-F) Western blot analysis of VEGFA and VEGFR2 protein in liver tissues and islets. (B) Numbers of islets. (G-J) mRNA analysis of VEGFA and VEGFR2 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group.CC BY-NC-ND · PubMed Central
Figure 7. Mechanism of VEGFB involved in insulin secretion of β-cells. VEGFB, vascular endothelial growth factor B.
Figure 7. Mechanism of VEGFB involved in insulin secretion of β-cells. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central

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Metadata

Authors
Luo, X., Li, R.-R., Li, Y.-Q., Yu, H.-P., Yu, H.-N., Jiang, W.-G., & Li, Y.-N.
Affiliations
  • Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Clinical Medicine, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Department of Stomatology Medicine, School of Oral Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Department of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2022-07-26
Volume
26
Issue
3
ISSN
  • 1791-2997
  • 1791-3004
DOI
10.3892/mmr.2022.12801
PMC
PMC9366154
Cited by
19
References
2

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