Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats.

The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.