Figure 1.
Metabolic characteristics of control mice and mice fed a high fat diet for 6 weeks.
A. Body weight (n = 13–14 mice). B. Food intake (n = 4 cages). C. Blood glucose concentrations during GTT (n = 6 mice). D. AUC blood glucose concentrations during GTT (n = 6 mice). E. Insulin concentrations during GTT (n = 5–6 mice). F. AUC insulin concentrations during GTT (n = 5–6 mice). G. Blood glucose concentrations during ITT (n = 8 mice). H. AUC of glucose concentrations during ITT (n = 8 mice). HFD = high-fat diet, AUC = area under the curve. *p<0.05, **p<0.01, ***p<0.001.
Figure 2.
Beta cell mass morphometry in control and HFD mice.
A. Beta cell mass in the entire pancreas after 6 weeks (n = 6 mice). B. Beta cell mass by pancreatic region after 6 weeks (n = 6 mice per region). C. Beta cell cluster area in the entire pancreas after 6 weeks (n = 6 mice). D. Beta cell cluster area by pancreatic region after 6 weeks (n = 6 mice per region). E. Islet density in the entire pancreas after 6 weeks (n = 6 mice). F. Islet density by pancreatic region after 6 weeks (n = 6 mice per region). G. Beta cell area in the entire pancreas after 12 weeks (n = 6 mice). H. Beta cell area by pancreatic region after 12 weeks (n = 6 mice per region). DR = duodenal region, GR = gastric region, SR = splenic region, HFD = high-fat diet. *p<0.05, #p<0.05 by unpaired Student's t test.
Figure 3.
Beta cell proliferation in control and HFD mice after 6 weeks.
A. Image of proliferating beta-cells (arrowheads), Ki67 (green), insulin (red) and DAPI (blue). Scale bar = 50 µm. B. Image of proliferating beta-cells (arrowheads), BrdU (brown) and insulin (red) per pancreatic region in control and HFD mice. Mice received BrdU during the final 7 days. Scale bar = 50 µm. C. Beta cell proliferation in the entire pancreas, BrdU labeling during the final 7 days (n = 6 mice). D. Beta cell proliferation by pancreatic region, BrdU labeling during the final 7 days (n = 6 mice per region). E. Cyclin D1 mRNA expression by pancreatic region, control = 1. DR = duodenal region, GR = gastric region, SR = splenic region, HFD = high-fat diet. *p<0.05, ***p<0.001
Figure 4.
Glucose-induced insulin secretion from isolated islets of control and HFD mice.
Insulin secretion was corrected for DNA content. A. Insulin secretion during 2 mM and 20 mM glucose stimulation from islets in the entire pancreas (n = 24). B. Insulin secretion from islets by pancreatic region during incubation in 2 mM glucose buffer (n = 8 per region) and C. 20 mM glucose buffer (n = 8 per region) for control and HFD mice. D. Insulin mRNA expression by pancreatic region, control = 1. DR = duodenal region, GR = gastric region, SR = splenic region, HFD = high-fat diet. *p<0.05, **p<0.01, ***p<0.001.
Figure 5.
Beta cell adaptation in islets grafts from different pancreatic regions transplanted in syngeneic diabetic mice.
A. Average islet size per transplant. B. Blood glucose concentrations of STZ-induced diabetic mice followed up to 10 days after transplantation (n = 6–8 mice per region) of DR, GR or SR islets. C. AUC blood glucose concentrations post-transplantation corrected for pre-transplantation glucose concentration (n = 6–8 mice per region). D. Image of proliferating beta-cells, positive for both BrdU (brown) and insulin (red) in islets transplanted under the kidney capsule of diabetic mice. Scale bar = 20 µm. E. Beta cell proliferation in the islet grafts 10 days after transplantation, BrdU labeling during the final 7 days (n = 6–7 mice per region). DR = duodenal region, GR = gastric region, SR = splenic region, AUC = area under the curve.