Role of FGF1, FGF2 and FGF7 in the development of the pancreas from control and streptozotocin-treated hamsters

Abstract

Although progress has been made with respect to the growth and transcription factors implicated in pancreatic development, many questions remain unsolved. It has been established that during embryonic life, both endocrine and acinar cells are derived from pancreatic epithelial precursor cells. Growth factors control the proliferation of precursor cells and their ability to differentiate into mature cells, both in pre-natal and in early post-natal life. Pancreatic development during the early post-natal period is an area of great interest for many scientists. In this study we have examined the structure characteristics, functional and proliferative activity of control and diabetic hamster pancreatic ductal, exocrine and beta cells, following treatment with FGFs 1, 2 and 7 in vitro. Light and electron microscopic studies indicated active synthetic processes in these cells under the influence of the investigated FGFs. In our experimental model of diabetes, the labelling index of the cells was significantly higher than in corresponding control groups of hamsters. We established that FGF2 at a concentration of 10 ng/l was responsible for the most prominent effect on ductal cells and beta cells in the diabetic groups. FGF1 at a concentration of 10 ng/l displayed the highest stimulatory effect on exocrine cells in the diabetic groups at post-natal day 10. Taken together these data strongly suggest that FGF1 and FGF2 induce proliferation of pancreatic epithelial cells during the early post-natal period whereas FGF7 is not strictly specific for pancreatic cell proliferation.

Figure 1

Islets of Langerhans throughout mesenchymal tissue in the pancreas of a control specimen, stage pnd 5, after treatment with 10 ng/l FGF7; IL, islet of Langerhans; Ac, acinar cells; asterisk‐mesenchymal tissue; H&E, ×25 magnification.

Figure 2

Portion of B cell in the pancreas of control specimen stage pnd 10 after treatment with 100 ng/l FGF1. N, nucleus; arrows, granules of β cell in different stages of maturation; ×30 000 magnification.

Figure 3

Marked nuclei in ductal epithelium of the diabetic group stage pnd 5, after treatment with 100 ng/l FGF1. Du, duct; L, ductal lumen; arrows, marked nuclei; ×100 magnification.

Figure 4

Proliferative activity of FGF‐untreated experimental groups (mean ± SE); h, FGF‐untreated healthy group; un. d, FGF‐untreated diabetic group; significant difference between FGF‐untreated healthy group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 5

Effect of 4 ng/l FGF1 on control and diabetic groups (mean ± SE); c, control group; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 6

Effects of 10 ng/l FGF1 on control and diabetic groups (mean ± SE); c, control; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 7

Effects of 100 ng/l FGF1 on control and diabetic groups (mean ± SE); c, control; d, diabetic groups; significant differences from control groups *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 8

Effects of 4 ng/l FGF2 on control and diabetic groups (mean ± SE); c, control; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 9

Effects of 10 ng/l FGF2 on control and diabetic groups (mean ± SE); c, control group; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 10

Effects of 100 ng/l FGF2 on control and diabetic groups (mean ± SE); c, control group; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 11

Effects of 4 ng/l FGF7 on control and diabetic groups (mean ± SE); c, control; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 12

Effects of 10 ng/l FGF7 on control and diabetic groups (mean ± SE); c, control group; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 13

Effects of 100 ng/l FGF7 on control and diabetic groups (mean ± SE); c, control group; d, diabetic group; significant differences from control group *P < 0.05; **P < 0.01; ***P < 0.001.