Effects of organic mercurials on mammalian pancreatic β-cells. Insulin release, glucose transport, glucose oxidation, membrane permeability and ultrastructure

Abstract

The effects of p-chloromercuribenzoic acid and chloromercuribenzene-p-sulphonic acid on pancreatic islets were studied in vitro. Obese-hyperglycaemic mice were used as the source of microdissected islets containing more than 90% beta-cells. p-Chloromercuribenzoic acid and chloromercuribenzene-p-sulphonic acid stimulated insulin release at concentrations of 0.01mm or above. This stimulation was significantly inhibited by the omission of Ca(2+) or the addition of adrenaline, diazoxide or 2,4-dinitrophenol. p-Chloromercuribenzoic acid or chloromercuribenzene-p-sulphonic acid did not interfere with the insulin-releasing ability of glucose. Micro-perifusion experiments revealed that the release of insulin in response to organic mercurial occurred almost instantaneously, was reversible, and was biphasic. The two mercurials inhibited glucose transport as well as glucose oxidation, and increased the mannitol and sucrose spaces of isolated islets. Compared with the effects on insulin release, those on glucose transport and membrane permeability were characterized by a longer latency and/or required higher concentrations of organic mercurial. Apart from a seemingly higher proportion of beta-cells exhibiting certain degenerative features, in islets exposed to 0.1mm-chloromercuribenzene-p-sulphonic acid for 60min, no significant differences with respect to beta-cell fine structure were noted between non-incubated islets and islets incubated with chloromercuribenzene-p-sulphonic acid or glucose or both. It is suggested that insulin release may be regulated by relatively superficial thiol groups in the beta-cell plasma membrane.

Transport of rubidium and sodium in pancreatic islets

“…Much smaller, if any, effects were noted in islets exposed to the other sulphydryl reagents tested. In view of the fact that chloromercuribenzene-p-sulphonic acid is by far the most potent initiator of insulin release (Bloom et al 1972;Hellman, Idahl, Lernmark, Sehlin & T&Ijedal, 1973a, b), the results support our hypothesis that organic mercurials stimulate insulin release through a direct action on the f8-cell plasma membrane leading to increased cation permeability (Bloom et al 1972).…”

“…The sucrose space was unaffected by all treatments except 1 mm chloromercuribenzene-p-sulphonic acid, which increased it (cf. Bloom, Hellman, Idahl, Lernmark, Sehlin & Taljedal, 1972). In addition to results obtained with each type of medium, the differences between parallel test and control incubations are given as mean values and s.E.…”

Heavy metals, islet function and diabetes development

“…105 In primary cultures of mouse pancreatic islet cells, mercuric chloride altered the intracellular calcium homeostasis and insulin secretion. 106,107 A report has shown that Minamata disease patients, who suffered from organic mercury poisoning from 1986 to 1994 (mean age: 63 years), had significantly elevated urine glucose levels. The authors suggested that increased mercury level in Minamata disease may enhance an incidence in diabetes.…”

The Role of Phosphoinositide 3-Kinase/Akt Signaling in Low-Dose Mercury–Induced Mouse Pancreatic β-Cell Dysfunction In Vitro and In Vivo

“…Recently, increased oxidative DNA damage and serum redox status have been detected in individuals exposed to mercury (23). Moreover, previous in vitro studies have shown that HgCl 2 altered intracellular Ca 2ϩ homeostasis in pancreatic ␤-cells isolated from mouse islets (24) and decreased insulin secretion from secretion granules isolated from toadfish islets (25). It has also been shown that an increased incidence of diabetes existed in patients with documented Minamata disease (MeHg poisoning) in Japan (26).…”