Normalization of pancreatic exocrine enzymes by islet transplantation in diabetic rats

Abstract

In an effort to evaluate the effectiveness of islet transplantation in correcting exocrine dysfunction, young male Lewis rats were made diabetic by i.v. streptozotocin injection. Diabetes status was confirmed by decrease in insulin and increase in blood glucose and glycosylated hemoglobin levels. Pancreatic islets were isolated from age-matched control syngeneic rats by collagenase digestion followed by purification through a Ficoll gradient. Islets (approximately 1200) were grafted to the liver by intraportal injection to animals at 8 weeks after diabetes was established. Transplanted rats were sacrificed 4 weeks after correction of hyperglycemia. Diabetes resulted in decrease in body weight. Transplantation reversed the body weight loss and led to a body weight gain. Diabetes resulted in a decrease in pancreatic amylase (1.4 +/- 0.4 U/mg protein compared with a control value of 121.9 +/- 3.2 U/mg protein) and a slight increase in lipase (87.3 +/- 5.5 U/mg protein compared with a control value of 69 +/- 4.7 U/mg protein). Transplantation completely normalized amylase (132.2 +/- 25.0 U/mg protein) and lipase (56.3 +/- 3.9 U/mg protein) in spite of an imperfect correction of blood insulin, glucose, and glycosylated haemoglobin levels in these rats. These data demonstrated that islet transplantation is very effective in correcting the exocrine enzyme changes resulting from diabetes. Evaluation of steady-state levels of amylase mRNA in these groups of animals by Northern blots showed a decrease in the amylase mRNA level in diabetes and a return to that of control in transplanted rats, indicating that the control of amylase expression is most likely at the pretranslational level.

Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes

“…We found reduced amylase expression in acinar cells of STZ-injected mice. Similar observations were reported in STZ-injected rats, in which the mRNA level of pancreatic amylase was decreased (10,13). However, this reduction of amylase expression exerted only a small, if any, effect on transdifferentiation capacity of acinar cells.…”

Dietary Branched-chain Amino Acids Suppress the Expression of Pancreatic Amylase mRNA in Rats

“…3). It has been reported that pancreatic amylase is regulated by several factors, such as insulin, [10][11][12][13][14][15] glucocorticoid, 26,27) and cholecystokinin (CCK). 25) Reduction of amylase by a low carbohydrate diet or a high protein diet has been explained by lowered insulin secretion with a reduction in dietary carbohydrate ingestion.…”

“…Although we also examined changes in insulin levels in the early stages of feeding, the relation of insulin levels in the early feeding period to pancreatic amylase activity cannot be determined due to large variation in insulin levels (data not shown). Because exogenous insulin [10][11][12] and endogenous insulin from transplanted B cells 13) restored amylase mRNA levels to a great extent in diabetic rats, insulin is probably important for the maintenance of amylase activity. But it has also been reported that exogenous insulin does not stimulate pancreatic amylase induction in normal rats.…”

“…8,9) Insulin is known to up-regulate pancreatic amylase mRNA and to prevent degradation of amylase mRNA in type 1 diabetes rats. [10][11][12][13] It has also been reported that amylase activity was lowered in a model rat with insulin resistance. 14) Moreover, a mouse pancreatic amylase gene, Amy-2.2, has an insulin-responsive element in the 5 0 -flanking region.…”

Leucine markedly regulates pancreatic exocrine secretion in goats

“…A number of recent studies have described that basal insulin levels are extremely essential for the mRNA expression and secretion of a-amylase in normal and diabetic rats (Lee et al, 1995;Hashimoto et al, 2004). It has also been suggested that leucine can improve tissue protein synthesis through the insulin-dependent (Rogero and Tirapegui, 2008) and insulin-independent (Lynch et al, 2002) mechanisms.…”