Antipancreatic Cellular Hypersensitivity in Diabetes Mellitus

Abstract

The occurrence of organ-specific, cellular hypersensitivity against pancreatic components was examined in twenty-two diabetics by means of the leucocyte migration test. An extract was prepared from pooled porcine pancreatic glands, in which atrophy of the exocrine tissue had been induced by ligation of the pancreatic duct. A specifically altered in vitro reactivity to the pancreatic preparation, consistent with a state of organ-specific, cellular hypersensitivity, was demonstrated in the diabetic group as compared to a control group. Intracutaneous injection of the same preparation in six diabetics with a positive in vitro reaction induced a typical delayed type reaction in four. DIABETES 20: 424-27, June, 1971. The literature on diabetes mellitus from early this century contained sporadic descriptions of mononuclear cell infiltration in and around the islets of Langerhans in the pancreas of patients suffering from diabetes. These reports did not attract much attention until it was later established that round cell infiltration of the endocrine pancreas was a frequent feature especially of infantile diabetes mellitus of short duration. 1 It has been emphasized 2 that the rarity of these histopathological changes is probably more apparent than real, as they are easily overlooked. In a recent, more extensive study, mononuclear cell infiltration, predominantly lymphocytes, could be demonstrated in and around the islets of Langerhans in 68 per cent of patients with juvenile diabetes mellitus of short duration. 3 As a qualitative phenomenon this cellular infiltration and the associated histopathological changes (in juvenile diabetes) cannot be distinguished from the ones found in autoimmune disorders in which organ-specific, humoral and/

Autoimmunity in Endocrine Disease

“…The observation by Nerup et al (1971) that a porcine duct-ligated pancreatic preparation can induce typical delayed type cutaneous reactions in diabetic patients with abnormal leukocyte migration tests lends further support to the theory that cell-mediated immunity to islet antigens is a feature of diabetes mellitus whether or not the diabetes has been treated with insulin, but no control experiments (e.g. using liver extracts) have been reported and are probably not justifiable.…”

The Discovery of Type 1 Diabetes

“…Three years later, Irvine et al (48) commented that "there seems to be a disorder of the immunological system related to insulin-dependent diabetes with respect to the formation of autoantibodies and the occurrence of organ-specific autoimmune disease," but did not suggest that diabetes was itself immune-mediated. Further provocative observations came in a series of reports from Nerup showing that the prevalence of Addison's disease and of adrenal antibodies was increased in insulin-dependent diabetes and, conversely, that diabetes developed more commonly in patients with Addison's (49).…”

Do post-translational beta cell protein modifications trigger type 1 diabetes?

“…Since the early 1970s, type 1 diabetes has been considered to be the result of an immune reaction against the beta cells [1][2][3]. The disease is multifactorial, with both environmental and genetic factors contributing to type 1 diabetes risk.…”