Selective beta-cell toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin on isolated pancreatic islets

Chemosphere ◽  
2021 ◽  
Vol 265 ◽  
pp. 129103
Author(s):  
Michela Novelli ◽  
Pascale Beffy ◽  
Matilde Masini ◽  
Chiara Vantaggiato ◽  
Luisa Martino ◽  
...  
1984 ◽  
Vol 107 (3) ◽  
pp. 382-389 ◽  
Author(s):  
J. Logothetopoulos ◽  
Nancy Valiquette

Abstract. We examined the relative changes in the rates of biosynthesis of (pro)insulin and of non-hormonal beta cell proteins in rats with pronounced hyperglycaemia for up to several days. Labelling of pancreatic cells in vivo eliminated certain pitfalls that we encountered when isolated pancreatic islets from these rats were labelled in vitro. Rats were infused with glucose or buffer solutions for 24 and 72 h. Glucose-infused rats had sustained hyperglycaemia throughout the infusion periods. l[4,5-3H]leucine or l[2,3-3H]tryptophan (an amino acid absent from proinsulin) was injected iv 30 min before the rats were killed. Pancreatic islets were isolated by enzymatic digestion of the pancreas. Pancreatic islets from the rats injected with [3H]leucine were processed for measurement of [3H]proinsulin and [3H]insulin by a double antibody immunoprecipitation procedure. Islets from rats injected with [3H]tryptophan were processed for autoradiography, in order to assess the incorporation of label into non-hormonal sedentary beta cell proteins. Incorporation of [3H]leucine into proinsulin and insulin per beta cell was estimated to be about 2–2.5 (24 h infusion) and 3.5–4 (72 h infusion) times greater in the hyperglycaemic than in normoglycaemic rats. Incorporation of [3H]tryptophan into non-hormonal beta cell proteins showed similar increments in the hyperglycaemic rats. Contrary to our expectation these results indicate that glucose does not exert a significant preferential effect on insulin biosynthesis even after sustained stimulation of the beta cells. Instead, glucose seems to increase equally the incorporation of labelled amino acids into proinsulin and into non-hormonal, beta cell proteins.


Diabetes ◽  
1988 ◽  
Vol 37 (9) ◽  
pp. 1226-1233 ◽  
Author(s):  
B. Portha ◽  
M. H. Giroix ◽  
P. Serradas ◽  
N. Welsh ◽  
C. Hellerstrom ◽  
...  

2005 ◽  
Vol 37 (11) ◽  
pp. 662-665 ◽  
Author(s):  
M. L. Grillo ◽  
A. P. Jacobus ◽  
R. Scalco ◽  
F. Amaral ◽  
D. O. Rodrigues ◽  
...  

2007 ◽  
Vol 192 (2) ◽  
pp. 389-394 ◽  
Author(s):  
Nguyen Khanh Hoa ◽  
Åke Norberg ◽  
Rannar Sillard ◽  
Dao Van Phan ◽  
Nguyen Duy Thuan ◽  
...  

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.


1996 ◽  
Vol 271 (4) ◽  
pp. C1098-C1102 ◽  
Author(s):  
A. Sjoholm

Preceding the onset of insulin-dependent diabetes mellitus, pancreatic islets are infiltrated by macrophages secreting interleukin-1 beta, which exerts cytotoxic and inhibitory actions on islet beta-cell insulin secretion through induction of nitric oxide (NO) synthesis. The influence of the NO donor 3-morpholinosydnonimine (SIN-1) on insulin secretion from isolated pancreatic islets in response to various secretagogues was investigated. Stimulation of insulin release evoked by glucose, phospholipase C activation with carbachol, and protein kinase C activation with phorbol ester were obtained by SIN-1, whereas the response to adenylyl cyclase activation or K(+)-induced depolarization was not affected. It is concluded that enzymes involved in glucose catabolism, phospholipase C or protein kinase C, may be targeted by NO. Reversal of SIN-1 inhibition of glucose-stimulated insulin release by dithiothreitol suggests that NO may inhibit insulin secretion partly by S-nitrosylation of thiol residues in key proteins in the stimulus-secretion coupling. These adverse effects of NO on the beta-cell stimulus-secretion coupling may be of importance for the development of the impaired insulin secretion characterizing diabetes mellitus.


1982 ◽  
Vol 86 (1) ◽  
pp. 121-124 ◽  
Author(s):  
Satoshi Yamamoto ◽  
Toshio Nakaki ◽  
Teruo Nakadate ◽  
Ryuichi Kato

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