6 Islet cell antibodies in diabetes

Abstract

CARL HENRIK BROGREN AKE LERNMARK The endocrine pancreas in insulin-dependent (type I) diabetes (IDD) is characterized by a severe loss of B cells (Gepts, 1965; Orci et al, 1976; Gepts and LeCompte, 1981). This loss appears to be highly selective since glucagon (A cells), somatostatin (D cells) and pancreatic polypeptide (PP- producing cells) remain in amounts similar to or higher than those in a normal pancreas (Orci et al, 1976; Gepts and DeMey, 1978). Recent estimations suggest that the total weight of the adult endocrine pancreas is about 1.5 g (Rahier, Wallon and Henquin, 1981) distributed among the four major endocrine cell types as follows: 65 per cent B cells, 17 per cent A cells, nine per cent D cells and nine per cent PP cells. At the time of diagnosis of IDD the decrease in endocrine pancreatic mass is mainly due to a 70 to 95 per cent loss of B cells (Gepts and LeCompte, 1981). The B cell depletion eventually leads to hypoinsulinaemia and an inability to control blood glucose. It is not clear to what extent the total B cell volume has to be reduced in order to affect the glucose homeostasis: what is the minimum number of B cells necessary to control blood glucose? Experimental surgery in animals and pancreatectomy in humans has indicated that overt diabetes does not develop provided that 20 to 30 per cent of the pancreas is allowed to remain (Martin and Lacy, 1963; Turner et al, 1979). Experiments in mice treated with multiple low doses of streptozotocin (Like and Rossini, 1976; Like et al, 1978) revealed that fasting hyper- glycaemia can still be prevented despite a 70 to 80 per cent loss in pancreatic islet cell volume (Bonnevie-Nielsen, Steffes and Lernmark, 1981). A significant factor in this respect is the close relationship between the total B cell volume and body weight: a decrease in total insulin reserve requires a parallel decrease in body weight to maintain glucose homeostasis (Martin and Lacy, 1963). It is notable that even if a major part of the B cell mass is lost the remaining B cells may be functionally more active, (i.e., synthesizing and releasing insulin at an increased rate compared to B cells in a normal pancreas). Functional studies in humans suggest that many newly diagnosed IDD patients have some residual B cell function (Block et al, 1972; Ludvigsson, S/~fwenberg and Heding, 1977; Binder and Faber, 1978; Madsbad et al, 1980a). Improved metabolic control in IDD patients increased the ability of the diabetic pancreas to release C peptide, (Madsbad