Insulin-resistant hyperglycemia produced by aminophylline.
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Biomedical subjects
Publications and source records attributed to L Recant.
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The biological activity of purified porcine proinsulin was investigated in rats. In vivo studies revealed that proinsulin produced a hypoglycemic response similar to insulin but of lesser magnitude. Hypophysectomized and adrenalectomized animals proved to be more sensitive to proinsulin than normal. In vitro studies with rat hemidiaphragm were consistent with the in vivo findings. No competition with insulin action could be demonstrated. Experiments were carried out to determine whether proinsulin is converted to intermediate forms or insulin as a requisite to its biological activity. Labeled proinsulin injected in vivo or incubated in vitro remained intact by a variety of techniques (Sephadex column chromatography and polyacrylamide-gel electrophoresis). An inhibitory action of Kunitz pancreatic trypsin inhibitor on proinsulin action in vitro was confirmed. No clarification of this effect could be ascertained.
Isolated rat islets of Langerhans were incubated for 60, 120, and 180 min and the incorporation of leucine-(3)H into proinsulin and insulin moieties was followed. Synthesis and release of these hormones could be followed by separate extractions of islets and incubation media. RELEASE OF NEWLY SYNTHESIZED PROINSULIN AND INSULIN OCCURRED UNDER THE FOLLOWING CONDITIONS: (a) incubation for greater than 60 min; (b) glucose concentrations above 5.3 mmoles/liter; (c) incubation with 5 mM dibutyryl cyclic AMP or theophylline in 5.3 mM glucose (potentiated by 16 mM glucose); and (d) incubation with 5 mM tolbutamide and 16 mM glucose. Synthesis of proinsulin and insulin was enhanced by time of incubation, high glucose concentrations, by dibutyryl cyclic AMP or theophylline, and by tolbutamide only at 16 mM glucose. Synthesis was totally inhibited by tolbutamide at 5.3 mM glucose.
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