The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6-250 micrograms in a 0.5-ml reaction volume (1.7 X 10(-6) to 2.7 X 10(-5) M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250-micrograms dose, was 6.5-fold greater than control for insulin secretion and 6.7-fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5-250 micrograms, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100-micrograms dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33 micrograms) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33- and 100-micrograms doses thereafter. At the 11-micrograms dose significant stimulation of hormone release was observed only after a 4-h incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate effects of circulating myelin basic protein (MBP) on the endocrine pancreas, we injected bovine MBP to Djungarian hamsters and studied the morphological changes induced by MBP and its immunocytochemical distribution by electron microscopy. After a treatment time of 5-40 min, some islets appeared severely damaged, especially at their peripheries and near the intraislet capillaries, while others showed minor or no changes. MBP-induced extracellular changes included partial disintegration of the collagen filament network surrounding the islet and the blood vessels. These changes correlated with the association of MBP with the collagen filament bundles and related structures. Intracellularly, the effect of MBP included formation of vacuoles, dilatation of rough ER and Golgi membranes, swelling and aggregation of mitochondria, and disruption of the membranes of part of the insulin and glucagon granules, as well as damage to some plasma membranes. In the damaged B cells, 16-62% of the insulin granules exhibited an enlarged pale core, compared to 1-2% in the control B cells. MBP was shown to associate with mitochondria and with various intracellular membranes in all islet cells. In the B cells, MBP was localized to the membranes of insulin granules, and it also associated with the cores of the granules. In the A cells, the association of MBP to the glucagon granules was mainly with the outsides of the membranes. Interaction of MBP with the secretion granules is suggested to play a role in MBP-induced insulin and glucagon release, and some hormone might be released by leakage. Association of MBP with mitochondria, Golgi structures, and ER may lead to changes in various cellular functions. Key Words: Electron microscopyInsulin granule-Islet of Langerhans-Membrane fusionMitochondria-Myelin basic protein.Myelin basic protein (MBP) is one of the most abundant proteins in the central nervous system (CNS) and accounts for approximately one-third of the total myelin protein. In most mammals the major form is the 18.5-kDa MBP, one of several MBP variants (1). A proposed role for MBP is the maintenance of the multilamellar structure of the myelin sheath by joining the opposite cytoplasmic faces of the membrane.MBP is able to aggregate and fuse lipid vesicles of various compositions by ionic or hydrophobic interactions and to release their contents in vitro (2). MBP also associates with itself and with other proteins (2) including intracellular proteins such as calmodulin (3) and actin (4). MBP-induced morphological changes in vitro in chicken erythrocytes (5) and functional changes in hu-
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