Insulin biosynthesis: Effects of carbohydrates and related compounds

Abstract

Incorporation of tritium-labeled leucine into proinsulin and insulin was used to indicate proinsulin synthesis and insulin formation. In these experiments the incorporation of labeled leucine into proinsulin and that into insulin were closely related. This incorporation was stimulated by addition of glucose and mannose but not by fructose. The glucose- and mannose-stimulated incorporation was inhibited by mannoheptulose. Inhibition by mannoheptulose was not relieved by addition of pyruvate. Pyruvate, with the addition of small amounts of fumarate and glutamate, failed to stimulate proinsulin and insulin synthesis even though insulin secretion was stimulated by tolbutamide or ribose. It was concluded that neither free glucose, nor pyruvate derived from glucose, acts as a signal to initiate biosynthesis. Possibly some more immediate metabolite of glucose or some enzyme or cofactor associated with its metabolism may be involved. Ribose and xylitol failed to stimulate the biosynthesis of proinsulin, and insulin. This, taken together with the reported stimulating effect of ribose and xylitol on insulin secretion, supports, for the islets, the postulate of Krass and LaBella for posterior pituitary hormones, that the pentose phosphate pathway is concerned with hormone storage and secretion rather than with hormone synthesis.

Dynamics of Insulin Release and Microtubular-Microfilamentous System. I. EFFECT OF CYTOCHALASIN B

“…In our opinion such an hypothesis is unlikely. Thus, cytochalasin B does not affect glucose-induced insulin biosynthesis and calcium uptake by isolated islets (3), although both of these processes are quite sensitive to alterations in glucose metabolism (19,26). Therefore, the facilitating action of cytochalasin B is nmore likely to be due to an altered response of the microtubular-microfilamentous system to the triggering action of intracellularly accumulated calcium rather than to a primary effect on glucose metabolism in the beta cell.…”

“…Received for publication 26 July 1972 and in revised form 20 November 1972. to inhibit the release of insulin evoked by glucose, leucine, theophylline, or sulfonylureas, suggesting that microtubules might govern the migration of secretory granules towards the cell membrane (1, 2, 57). Cytochalasin B, which affects the microfilamentous cell web, was found to facilitate insulin release in response to glucose, theophylline, or sulfonylurea, suggesting that the cell web might act as a barrier controlling the access of secretory granules to the cell membrane (3,8).…”

Effects of Xylitol and Glucose on Insulin Release from Dog Pancreas Tissue <I>in vitro</I>

“…One explanation may be that, in in vivo experiments, xylitol is rapidly metabolized in pancreatic islets and intermediate substance stimulates insulin secretion as it is metabolized in liver (Krebs et al, 1966) and adipose tissue (Mori et al, 1967), although the results of Montague and Taylor (1968) disagree. Another possibility is that the high concentrations of glucose stimulate the biosynthesis of insulin (Howell and Taylor, 1967 ;Lin and Haist, 1969) and proinsulin and newly synthethized insulin appear in the medium after 60 min of incubation (Steiner, 1967), while xylitol may not have this effect (Lin and Haist, 1969 ments. One reason may be that this experiment was done to the fasting dog, since the effect of mannoheptulose was more potent on the pancreas tissue from the fasted animal (Malaisse et al, 1967b).…”

High-resolution two-dimensional polyacrylamide gel electrophoresis reveals a glucose-response protein of 65 kDa in pancreatic islet cells.

“…Insulin release is stimulated (1) and insulin biosynthesis is augmented within minutes after glucose levels increase (2)(3)(4). If hyperglycemia persists for hours or even longer p cells become sensitized to glucose and ultimately they respond with hypertrophy and hyperplasia (5).…”