Lipid and exocrine pancreatic ultrastructural changes due to experimental diabetes

Abstract

The aim of this study was to establish if the changes in the ultrastructure of the exocrine part of the pancreas are correlated with changes in serum glucose, cholesterol and lipoprotein fractions during the progression of diabetes in rabbits. Diabetes mellitus was induced in male New Zealand rabbits by a single injection of alloxan into the auricular vein. On the day 7th the glucose level in the whole blood was measured and this day was designated as the first day of diabetes. Rabbits were divided into 5 groups: untreated control, 21-day diabetes, 42-day diabetes, 90-day diabetes and 180-day diabetes. The cholesterol, HDL (high-density lipoprotein) and LDL (low-density lipoprotein) levels were examined in the serum. The total pancreatic lipase activity was measured spectrophotometrically in the pancreatic homogenate. Histological specimens were examined under an electron microscopy. The glucose level increased significantly in all of the alloxan exposed animals. The significant elevation of cholesterol level was observed on day 21 and 180. The HDL level was increased (P<0.05) only on the day 21st. The LDL level and the total activity of pancreatic lysosomal lipase increased significantly on day 21, 42 and 90. Further dilation of granular endoplasmic reticular ducts and decrease in the number of zymogen granules were observed amongst exocrine cells. Fragmented mitochondrial and translucent matrix were also seen. Intensification of the pancreatic fibrosis was found on day 90. Microvascular changes were reported in exocrine cells after 180 days. Their nuclei were smaller with large bulges on the nuclear membrane, and the number of heterogeneous electron granules of zymogen further declined. We concluded that the intensification of ultrastructural changes of the exocrine part of the pancreas correlated with the changes of the pancreatic lipase activity, and glucose and lipoprotein levels.

Serum amylase activity disorders in the course of experimental diabetes in rabbits

“…It seems that the initial drop in the serum α-amylase activity may be interpreted by the impaired pancreatic exocrine secretion due to a decrease in the insulin stimulatory action (Aughsteen and Kataoka, 1993;Hegyi et al, 1999;Hardt et al, 2000;Shimizu et al, 2000). Transient increase in enzyme activity on day 90 of the experiment may reflect the release of the enzyme from cellular compartments caused by increased destructive processes, which is consistent with observations on the ultrastructural level (Ahren and Sundkvist, 1995;Maciejewski et al, 1999aMaciejewski et al, ,b, 2001). The following decrease in enzyme activity is a result of definite depletion of α-amylase reserves as well as its impaired synthesis in the exocrine cells.…”

“…The observed systemic and metabolic disorders were accompanied by relevant transformations on the ultrastructural level. The number and intensity of these changes were proportional to the disease duration as described by the authors in their previous studies (Maciejewski et al, 1999a(Maciejewski et al, ,b, 2001). …”

“…The current study is a continuation of a larger project, with partial results having been published previously (Maciejewski et al, 1999a(Maciejewski et al, ,b, 2001). Choosing serum α-amylase as an indicator of the exocrine pancreatic function is based on the enzyme's relative stability, long breakdown period, high sensitivity and specificity, in comparison with other pancreatic enzymes being also used in daily clinical practice.…”

“…according to the guidelines of good animal practice (Maciejewski et al, 1999a(Maciejewski et al, ,b, 2001.…”