Proinsulin synthesis in islets of Langerhans from spiny mice (Acomys cahirinus). comparison with rats and mice

Abstract

Summary. Proinsulin synthesis in response tO different concentrations of glucose has been studied in islets of Langerhans of acomys, rat and mouse. The response to increased glucose was small in acomys when compared with rat or mouse. The time course of the effect of glucose on proinsulin synthesis was also studied in sequential 15 min periods up to 60 min. With 5.5 mM glucose the rate of 3H-leucine incorporation for acomys islets was greater over the periods 15-30, 30-45 and 45-60 min after the addition of glucose to the islets than at 0-15 rain. By contrast rat islets exhibited a greater glucose-induced stimulation between 15-30 and 30-45 min relative to the 0-15 min period and a further increase of the incorporation rate between 45 and 60 min. With 27.5 mM glucose acceleration of incorporation relative to the first 15 min period occurred at 15-30 min; it was then stable up to 60 min for islets both from acomys and from rat. Incorporation into total protein was much greater in acomys than in rat or mouse: thus in 2.75 mM glucose, acomys islets incorporated 5 and 19 times more 3H-leucine into total protein than did islets from rat or mouse respectively. In 27.5 mM glucose the incorporation into total protein of the islets from acomys was 4 and 13 times greater. Islet content of insulin was similar for all three species. No significant changes in ATP content were observed in response to changes in glucose concentration from 2.75 to 27.5 mM. The results demonstrate a decreased responsiveness of proinsulin synthesis to glucose in acomys and are discussed in terms of the known decreased sensitivity of insulin release in this animal. Acomys cahirinus maintained in the Geneva colony exhibit hyperplasia of the islets of Langerhans [1][2][3] and a retarded as well as reduced rate of insulin release in response to glucose challenge by comparison with rats or mice [4][5][6][7]. These differences in the response profile to glucose have been detected in vivo, after either intraperitoneal [4][5] or intravenous [6] glucose injection, and in vitro, using isolated islets [7][8][9]. While acomys islets respond slowly to glucose, the total release of insulin over a two hour period may be comparable to that of rats, at least at higher glucose concentrations [7][8][9], suggesting predominantly early decreased sensitivity to glucose. Indeed, when the early and late release phases were compared in some detail [7][8][9], it was confirmed that the early phase (1-10 rain) of insulin release from acomys islets exhibited both decreased sensitivity to glucose and a decreased release capacity. By contrast, the late phase (20-30 rain) of insulin release from acomys islets exhibited only decreased sensitivity to glucose. As these time/secretion characteristics resemble in some respects observations reported in latent diabetes as well as maturity onset diabetes in man [10][11][12] acomys has attracted attention as a possible "model" of potential usefulness. Because of this and because the insensitivity to glucose might be carried over to the ...

Glucose stimulated proinsulin biosynthesis

“…and the mixture centrifuged at 4000 • g for 30 minutes. This procedure gives identical recovery to acid-ethanol extraction according to the method of Davoren [18] as shown previously [10,11]. A 0.5 ml aliquot of the supernatant was then placed on 0.9 x 2.0 cm columns of CNBr-activated Sepharose 4B (Pharmacia, Uppsala, Sweden) covalently linked to anti-insulin antibodies [12,[19][20][21] and equilibrated with 0.2 mol/1 glycine buffer 2.5 g/1 HSA pH 8.8.…”