Cellular composition of the human diabetic pancreas

Abstract

Insulin, glucagon, somatostatin and pancreatic polypeptide cells were stained by immunoperoxidase techniques and quantitated morphometrically in sections of pancreases obtained from eight control subjects, four Type 1 (insulin-dependent) and eight Type 2 (non-insulin-dependent) diabetic patients. The whole pancreas was studied to take into consideration the heterogeneous distribution of the different cell types. From the volume density of each cell type, and the weight of each lobe of the pancreas, the total mass of endocrine tissue was calculated. It averaged 1395 mg in control subjects, 413 mg in Type 1 and 1449 mg in Type 2 diabetic patients. The loss of endocrine tissue observed in the Type 1 patients was almost restricted to the lobe poor in pancreatic polypeptide cells. In these patients, B cells were practically absent (at the most seven per section), but the 'atrophic islets' still contained numerous A, D, or pancreatic polypeptide cells. The mass of A, D and pancreatic polypeptide cells and the ratio of D to A cells were not different from those measured in the control subjects. This shows that the disappearance of B cells in Type 1 diabetes has no preferential effect on any other endocrine cell of the pancreas. In Type 2 diabetes, the mass of A cells was increased, whereas that of B, D and pancreatic polypeptide cells was not changed. This hyperplasia of A cells leads to a decrease in the ratio of B to A and of D to A cells. These alterations may enlighten certain aspects of the physiopathology of Type 2 diabetes.

Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment

“…Hence, insulin-deficient islets composed of normal numbers of alpha cells were found in the autopsied pancreas in 11 children with recent-onset type 1 diabetes [6], and no difference in alpha cell number was found between 11 juvenile diabetic patients and control subjects [7]. Furthermore, the mass of alpha, delta and pancreatic polypeptide cells and the ratio of delta to alpha cells in four type 1 diabetes patients did not differ from those in control subjects [8]. All these findings suggest that beta cells undergo specific damage in autoimmune type 1 diabetes, which may be promoted by the selective recognition of beta cell antigens by T cells.…”

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.…”

“…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).…”

“…In patients with type 2 diabetes the number of A-and D-cells is increased (Iki and Pour 2007), whereas the ratio of D-to A-cells is decreased (Rahier et al, 1983;Iki and Pour 2007). Pancreatic SST content of spontaneously diabetic adult ob/ob and db/db mice is increased (Makino et al, 1979).…”

Determinants of glucose control in patients with chronic pancreatitis

“…In type 2 diabetes, hyperglycaemia has been associated with a deficit in beta cell mass of ∼20-65% of normal [5][6][7][8][9][10][11], and studies in rodent models of autoimmune diabetes or in patients with newly onset type 1 diabetes indicate that the extent of beta cell loss amounts to ∼50-70% around the manifestation of type 1 diabetes [12][13][14]. Diabetes is also frequently found in patients with chronic pancreatitis (CP), secondary to the inflammatory process within the pancreas [15][16][17].…”