Alterations in somatostatin and other islet cell functions in the spontaneously diabetic BB Wistar rat: biochemical and morphological characterization

Abstract

In the present study we have attempted to assess the functional status of somatostatin cells in relation to the function of the other islet cell types (B, A, and PP cells) in the BB Wistar rat. Somatostatin-like immunoreactivity (SLI), glucagon, and insulin were measured in extracted plasma obtained from the hepatic portal vein (PV) and inferior vena cava (IVC) of acutely diabetic untreated rats, insulin-treated diabetic rats and nondiabetic controls. Extracts of the pancreas were assayed for SLI, glucagon, and insulin, and the pancreatic populations of A, B, D, and PP cells were evaluated by morphometry. Extrapancreatic somatostatin changes were assessed by measurement of SLI in extracts of the whole gut, hypothalamus, and retina. Direct studies of SLI, glucagon, and insulin secretion in response to glucose, arginine, and theophylline were carried out using the isolated perfused pancreases of two separate groups of untreated diabetic and nondiabetic rats. Our results showed that in the severely insulin deficient BB Wistar rat (1) pancreatic concentrations of SLI, glucagon, and insulin were reduced; (2) the B cells are virtually eliminated and the D cells severely reduced early in diabetes; A and PP cells are resistant initially but eventually sustain major losses as observed in terminal islets; (3) retinal SLI is reduced, but SLI in gut and brain appears unchanged; (4) the secretion of SLI, glucagon, and insulin from the perfused pancreas is diminished 60%, 36%, and 99%, respectively; (5) PV and IVC blood levels of SLI and glucagon are elevated despite decreased pancreatic secretion; (6) The trans-hepatic gradient of SLI is reduced; and (7) Insulin treatment normalizes the elevated PV and IVC levels of SLI and glucagon. It is concluded that the elevated PV and IVC levels of SLI are secondary to insulin deficiency and result from increased SLI secretion most probably from the gut and from diminished hepatic metabolism. The origin of the hyperglucagonemia is less certain, but as in the case of SLI, important contributions from extra-pancreatic secretion appears likely.