Stimualtion of Beta Cell Neogenesis by SBTI (Soybean Trypsin Inhibitor) or Soybean Diet in the Subtotal Pancreatectomy Models

Kim, So Yoon; Lee, Seung Hee; Min, Bon Hong; Park, In Sun

Abstract

The present study was performed to corroborate our hypothesis that soybean diet or SBTI treatment could stimulate neogenic regeneration of pancreatic beta cells, but also increase insulin synthesis and secretion from the beta cells for correction of hyperglycemia and diabetic symptoms. We, thus, monitored the beta cell regeneration in the neogenic pancreas as well as the changes of the blood glucose and insulin levels after subtotal pancreatectomy. The diabetic animals with hyperglycemia induced by the subtotal pancreatectomy showed recovery of blood glucose level toward the normal range (<150 mg/dl) by giving raw soybean for 3~4 weeks. Most animals treated with SBTI remained in euglycemic condition in spite of diabetic induction by subtotal pancreatectomy. Their serum insulin level was also recovered to the level of normal control, indicating the increased insulin synthesis and secretion from the neogenic beta cells. Neogenic area was enlarged at least 2 times in the pancreatectomized rats with dietary soybean or SBTI treatment, when compared with their pancreatectomized controls without any dietary treatment. In neogenic tissue, few endocrine cells were detected as a single cell or cell cluster at 3 days, and they formed primitive islet at 7 days after pancreatectomy in non-treated controls. The numbers of beta cells as well as alpha cells were considerably increased in the SBTI treated rats, and early formation of primitive islets were found in the neogenic tissue of those animals at 3 days after pancreatectomy. Those beta cells demonstrated a strong immunoreactivity for insulin, indicating their bioactive insulin secretion. Clusterin, a marker protein for pancreatic neogenesis, was expressed in the wider pancreatic area and at earlier stage after pancreatectomy when compared with non-treated control rats, indicating acceleration and stimulation of neogenesis of pancreas by stimulating proliferation and differentiation of the functional pancreatic cells. Taken together, we concluded that dietary soybean and SBTI could stimulate beta cell neogenesis and induce activation of insulin synthesis and secretion from the neogenic beta cells for correction of glucose homeostasis in diabetic subjects.