Glucose stimulated proinsulin biosynthesis

Kaelin, D.; Renold, Albert E.; Sharp, Geoffrey W. G.

doi:10.1007/bf01223025

Cited by 19 publications

(5 citation statements)

References 22 publications

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“…In accordance with [15] but not with [10,19,21] we found no inhibition of (pro)insulin biosynthesis after incubation of islets of fed Wistar rats with actinomycin D for periods up to 4 h. The rate of (pro)insulin biosynthesis was not inhibited either by incubation of islets of fed Wistar rats with a-amanitin, a specific inhibitor of mRNA synthesis [30,31]. The inhibition of mRNA synthesis by a-amanitin was extended to two days in cultivated islets.…”

Section: Discussionsupporting

confidence: 89%

“…Studies on the kinetics of glucose stimulation of (pro)insulin biosynthesis were consistent with this conclusion [7,10]. Participation of transcriptional control of (pro)insulin biosynthesis during 1 hour of incubation of islets of fed rats was suggested from experiments measuring the rates of turn-off after cessation of the glucose stimulus [21].…”

Section: Discussionmentioning

confidence: 53%

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Transcriptional and Translational Control of Glucose‐Stimulated (Pro)insulin Biosynthesis

Jahr

Schroder

Ziegler

et al. 1980

European Journal of Biochemistry

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Islets of Langerhans were isolated from the pancreata of fed or 48-h-fasted Wistar rats. The islets were incubated with either [3H]leucine of [3H]uridine. Inhibition of RNA synthesis by actinomycin D or by cx-amanitin for 4 h had no influence on the (pro)insulin biosynthesis of isolated islets of fed rats. The (pro)insulin biosynthesis was not inhibited after two days incubation of islets of fed rats with a-amanitin either. Incorporation of labelled uridine into total RNA for 3 h was stimulated by glucose in islets of fasted, but not of fed rats. Therefore, it was concluded that transcriptional control does not participate, even for longer periods than believed previously, in acute regulation of (pro)insulin biosynthesis of islets isolated from fed rats. Despite the strong and preferential stimulation of (pro)insulin biosynthesis of islets of fed rats by glucose the radioactivity of the [3H]uridine-labelled polysomes active in proinsulin synthesis remained unchanged.To interprete these experimental data we suggest that glucose triggers the transformation of a translationally inactive form of pre-proinsulin mRNA to a translationally active form.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 53%

Transcriptional and Translational Control of Glucose‐Stimulated (Pro)insulin Biosynthesis

Jahr

Schroder

Ziegler

et al. 1980

European Journal of Biochemistry

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“…In these experiments, intracellular insulin content was reduced in cells treated with 800 kHz ultrasound (as represented by the negative change in intracellular insulin) while it appears to have increased in the sham group (as represented by the positive change in intracellular insulin). We believe that the increased insulin content in the sham group may be due to potential factors such as extracellular insulin uptake through endocytosis or continuous insulin synthesis (Eliasson et al 1996; Kaelin et al 1978; Orci et al 1973; Rorsman and Renström 2003). Though the general trends of insulin release measurements into the extracellular space and changes in intracellular insulin concentration are in good agreement, their measured magnitudes appear to be notably different.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes

Castellanos

Jeremić

Cohen

et al. 2017

Ultrasound in Medicine & Biology

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Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and eventually destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that utilizes the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at peak intensity of 1 W/cm2 and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay (ELISA) and cell viability was assessed via trypan blue dye exclusion test. A marked release (approximately 150 ng/106 cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 kHz and 600 kHz as compared to their initial control values, however this release was accompanied with a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/106 cells of released insulin (p < 0.05) as compared to its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800 kHz ultrasound was comparable to that reported by secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has a potential to find an application as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.

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“…An effect of glucose at the translational level has been shown to occur immediately after addition of glucose to incubation medium, leading to an increase in the number ofpolysomes active in protein synthesis by enhancing initiation of all islet mRNA (29). Another component of glucose-stimulated insulin synthesis may involve new mRNA synthesis (24,30). Rats fasted for [3][4] days have an 80% decrease in proinsulin mRNA levels (25).…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of rat insulins I and II: evidence for differential expression of the two genes.

Kakita¹,

Giddings²,

Permutt³

1982

Proc. Natl. Acad. Sci. U.S.A.

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The purpose of these experiments was to determine the relative content and biosynthetic rate of insulins I and II under various experimental conditions. The two insulins were quantitated by polyacrylamide gel electrophoresis, electrotransfer to nitrocellulose paper, photoaffinity crosslinking, and immunodetection with anti-insulin antibody and '5I-labeled protein A. The ratio (mean ± SEM) of insulins, I/HI, was 1.2 ± 0.2 in Wistar-Furth rats fasted for 4 days, 1.6 ± 0.2 in normal rats, and 5.5 ± 0.8 in growth hormone-tumor-bearing hyperinsulinemic rats (P < 0.01). The increase in content of rat insulin I compared to II in the growth hormone-tumor-bearing animals was confirmed by radioimmunoassay ofgel slices. To determine whether the difference in contents of rat insulins Iand El in the hyperinsulinemic rats was due to increased biosynthesis or a different turnover rate, isolated rat islets were incubated in [3H]leucine for 4 hr with 5.5 mM or 16.0 mM glucose in the incubation medium. Glucose stimulated insulin biosynthesis >8-fold. The ratio of synthesis of rat insulin I relative to II was 0.9 ± 0.1 at 5.5 mM glucose and 9.8 ± 3.3 (P < 0.01) at 16.0 mM glucose. Therefore, under conditions that stimulate insulin biosynthesis, there was a marked preferential synthesis ofrat insulin I relative to H. These studies suggest that the two rat insulin genes are expressed independently and that, under stimulatory conditions, there is preferential expression of the rat insulin I gene.In rats (1, 2), mice (3, 4), and certain fish (5, 6), two different insulins have been found. The rat insulins have been shown to be encoded by two nonallelic genes separated by at least 9,000 base pairs of DNA (7,8). The mRNAs are quite similar, approximately 93% homologous in the coding regions with only 34 of 439 nucleotides different (9, 10). Preproinsulins I and II, the initial translation products, differ by three amino acids in the preregion (7-11), two in the B chain, and two in the C peptide (see Fig. 1).Although the structures of the two genes, RNAs, and preproinsulins have been completely determined, little is known about the regulation of expression of the individual genes. In insulin isolated from Sprague-Dawley rat pancreas by Clark and Steiner (2), analysis by polyacrylamide gel electrophoresis indicated 58% insulin I and 42% insulin II. Biosynthesis of rat insulins I and II has been shown to occur in a ratio of 60:40 in several studies (2,(12)(13)(14).The present experiments were initiated in the course of the development ofan immunoelectrophoretic method for studying pancreatic extracts of insulin. We noted, in a hyperinsulinemic rat, that the ratio of rat insulins, I/IL, appeared to be greater than 5:1, a value very different from that previously reported. We therefore decided to do a more complete analysis of the proportion of rat insulins I and II under various experimental conditions and to examine their relative rates of synthesis. Our analysis confirmed that both the steady-state content and synthesis ofrat ins...

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Glucose stimulated proinsulin biosynthesis

Cited by 19 publications

References 22 publications

Transcriptional and Translational Control of Glucose‐Stimulated (Pro)insulin Biosynthesis

Transcriptional and Translational Control of Glucose‐Stimulated (Pro)insulin Biosynthesis

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes

Biosynthesis of rat insulins I and II: evidence for differential expression of the two genes.

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