Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes.

Abstract

Insulin-, glucagon-, and somatostatin-containing cells, identified by immunofluorescent staining, were quantitated morphometrically in sections of pancreas obtained from diabetic and nondiabetic humans and rats. Both the volume density and number of somatostatin-and glucagon-containing cells were The other diabetic pancreas was obtained from a 31-yearold white female with a 29-year history of juvenile-type diabetes who died of renal insufficiency. Grossly, the pancreas was indurated and microscopic examination revealed acute pancreatitis. Islets were sparse and small, consisting largely of A-cells. No B-cells were noted.The four nondiabetic pancreases were obtained from encephalographically dead kidney donors in Geneva and Dallas in accordance with local regulations.Streptozotocin Diabetic and Nondiabetic Rats. Pancreases were obtained from four normal control rats and four rats with 16 months of diabetes produced by a single intravenous injection of 45 mg of streptozotocin per kg of body weight. These rats never required insulin treatment, but all were glycosuric at the time of sacrifice.Immunofluorescent Staining Techniques. The indirect immunofluorescent technique of Coons et al. (25) was employed with use of a rabbit anti-somatostatin serum (a gift of Dr. M. P. Dubois) at a dilution of 1:50, highly specific rabbit anti-glucagon serum 15K at a 1:20 dilution, and a guinea pig anti-insulin serum (a gift of Dr. P. H. Wright) at a 1:50 dilution. Anti-rabbit or anti-guinea pig gamma globulin labeled with fluorescein isothiocyanate (Pasteur Institute, Paris) was employed as the second antibody.Control experiments were performed using the specific antiserum absorbed with the corresponding antigen, 200,g of cyclic somatostatin (a gift of Drs. J. Rivier and R. Guillemin), 50 jig of glucagon, or 2 units of insulin per ml of undiluted antiserum. After removal of the paraffin, sections were rehydrated and incubated for 2 hr with anti-somatostatin, anti-insulin, or anti-glucagon serum. After rinsing in phosphate-buffered saline, the sections were incubated with the fluorescein-labeled antibody for 1

Acute effects of alloxan- and streptozotocin-induced insulin deficiency on somatostatin and glucagon secretion by the perfused isolated rat pancreatico-duodenal preparation

“…Administration of exogenous somatostatin inhibits the release of insulin and glucagon [8,9]. These observations, together with those of D cell hyperplasia and hypertrophy and of increased pancreatic somatostatin-like immunoreactivity in streptozotocin-and alloxaninduced diabetes in the rat [10][11][12] and in human insulin-dependent diabetes [13], suggest that somatostatin exhibits an important role in the physiology of islet function and possibly in the pathophys.-iology of diabetes.It has recently been reported that plasma somatostatin-like immunoreactivity is elevated in alloxan diabetic dogs [14] and in streptozotocin diabetic rats [15] and that somatostatin secretion from the isolated perfused pancreas of alloxan diabetic rats is exaggerated in response to arginine [16]. In another study, by contrast, normal pancreatic somatostatin responses to arginine, isoproterenol and calcium and a diminished response to glucose were seen in streptozotocin diabetic dogs [17].…”

“…Administration of exogenous somatostatin inhibits the release of insulin and glucagon [8,9]. These observations, together with those of D cell hyperplasia and hypertrophy and of increased pancreatic somatostatin-like immunoreactivity in streptozotocin-and alloxaninduced diabetes in the rat [10][11][12] and in human insulin-dependent diabetes [13], suggest that somatostatin exhibits an important role in the physiology of islet function and possibly in the pathophys.-iology of diabetes.…”

Function and expression of somatostatin receptors of the endocrine pancreas

“…On the other hand it is possible that SSTRs are upregulated as a defense mechanism against hyperglucagonemia. Previous studies demonstrated a hyperplasia and hypertrophy of pancreatic D-cells in type 1 and type 2 diabetes (Rahier et al, 1983;Orci et al, 1976;Iki and Pour 2007;Gomez Dumm et al, 1995). Thus, both the increase in SST production as well as SSTR Page 9 of 29 A c c e p t e d M a n u s c r i p t 9 expression on A-cells could provide a defense mechanism against hyperglucagonemia; however, experimental evidence supporting this hypothesis remains to be established.…”

“…Treatment with insulin normalized the elevated basal plasma SST levels in these patients (Segers et al, 1989). Animals with streptozotocin-induced diabetes and NOD mice with autoimmune diabetes have increased size and number of D-cells as well as increased pancreatic SST content (Orci et al, 1976;Gomez Dumm et al, 1995;Kanatsuka et al, 1981).…”

“…Patients with type 1 diabetes were reported to have increased number of D-cells, whereas the ratio of Dto A-cells was decreased due to A-cell hyperproliferation (Orci et al, 1976;Rahier et al, 1983). Type 1 diabetic patients had elevated basal plasma SST concentrations (Skare et al, 1985;Segers et al, 1989) and increased responsiveness of pancreatic D-cells to arginine, whereas the overall prandial SST levels was reduced (Skare et al, 1985).…”