The pancreatic islet monosialo-
ganglioside (GM2-1), an
autoantigen in
insulin-dependent diabetes mellitus (
IDDM) recently shown to be the target of
autoantibodies associated with diabetes development in relatives of
IDDM patients, is islet specific within the pancreas, and its expression is metabolically regulatable. In the present study we sought to establish 1) whether GM2-1 is beta-cell specific, and 2) its intracellular localization. To this end, we analyzed the pattern of
ganglioside expression in highly purified beta- and non-beta-cells isolated from rat islets. In addition,
ganglioside levels were determined in subcellular fractions of a rat beta-cell line (INS). No qualitative or quantitative difference was found in the pattern of
ganglioside expression between beta and non-beta rat islet cells, with GM3, GM2-1, and GD3
gangliosides expressed in both cell populations. Within INS cells, GM2-1
ganglioside was expressed in the fraction containing secretory granules and, to a lesser extent, in plasma membranes; GM3 was expressed in secretory granules, whereas GD3 was found only in plasma membranes. These data indicate that the GM2-1
autoantigen is not beta-cell specific within the islets, in accordance with the observation that this molecule is a target of islet cell
autoantibodies that bind to the whole pancreatic islet. Interestingly, this
autoantigen is present in secretory granules similarly to other
autoantigens in
IDDM (
insulin,
carboxypeptidase H, 38-kDa
protein, etc.), suggesting that the autoimmunity to the components of this organelle may be central to the pathogenesis of the disease.