Pancreatic metallothionein: Protection against cadmium-induced inhibition of insulin secretory activity*1

Yau, E. T.; Mennear, John H.

doi:10.1016/0041-008x(77)90142-9

Cited by 29 publications

(5 citation statements)

References 13 publications

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“…Unsurprisingly, this is also the case in pancreatic islets and beta-cells. Thus, earlier evidence has shown that Cd administration upregulated MT protein levels in the mouse pancreas [73]. In agreement, exposure of the mouse beta-cell line MIN6 to Cd augmented MT1 and MT2 protein levels [79].…”

Section: Regulation By Metalssupporting

confidence: 68%

“…However, when mice were pretreated with Cd prior to islet isolation which upregulated MT protein levels in the pancreas, subsequent exposure of isolated islet to Cd did not reduce GSIS. This was the first study suggesting a protective role of MT in beta-cell against acute Cd toxicity [73]. Similarly, pretreatment of mice with Zn-enriched drinking water increased islet MT protein levels and partially protected against diabetes induced by multiple low doses of STZ [75].…”

Section: Adaptive Roles Of Mts In Beta Cellsmentioning

confidence: 65%

“…The presence of constitutive and/or inducible MT expression in mouse and human islets has been known for decades [73][74][75][76]. Analysis of more recent RNA sequencing data of purified mouse islet cell preparations revealed that Mt1 and Mt2 were strongly expressed in beta-cells in comparison to the stress response gene Hmox1, the beta-cell enriched gene Pdx1 or the house-keeping gene Ppia, for example, with Mt1 exhibiting relatively higher mRNA levels than Mt2.…”

Section: Expression Of Metallothionein Genes In Mouse and Human Beta mentioning

confidence: 99%

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Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and above Metal Homeostasis and Antioxidant Response

Bensellam

Laybutt

Jonas

2021

Biology

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Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins whose precise biological roles have not been fully characterized. Existing evidence implicated MTs in heavy metal detoxification, metal ion homeostasis and antioxidant defense. MTs were thus categorized as protective effectors that contribute to cellular homeostasis and survival. This view has, however, been challenged by emerging evidence in different medical fields revealing novel pathophysiological roles of MTs, including inflammatory bowel disease, neurodegenerative disorders, carcinogenesis and diabetes. In the present focused review, we discuss the evidence for the role of MTs in pancreatic beta-cell biology and insulin secretion. We highlight the pattern of specific isoforms of MT gene expression in rodents and human beta-cells. We then discuss the mechanisms involved in the regulation of MTs in islets under physiological and pathological conditions, particularly type 2 diabetes, and analyze the evidence revealing adaptive and negative roles of MTs in beta-cells and the potential mechanisms involved. Finally, we underscore the unsettled questions in the field and propose some future research directions.

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Section: Regulation By Metalssupporting

confidence: 68%

Section: Adaptive Roles Of Mts In Beta Cellsmentioning

confidence: 65%

Section: Expression Of Metallothionein Genes In Mouse and Human Beta mentioning

confidence: 99%

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Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and above Metal Homeostasis and Antioxidant Response

Bensellam

Laybutt

Jonas

2021

Biology

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“…Cadmium is also well known as a very potent inducer of metallothionein (9,17,18), a metal-binding protein that appears to be important in the biologic response to cadmium in most tissues (17), including the pancreas (18,23). Acute and chronic exposure to cadmium can in fact stimulate metallothionein production in the pancreas (4,8,23 (2,10).…”

Section: Introductionmentioning

confidence: 99%

“…Acute and chronic exposure to cadmium can in fact stimulate metallothionein production in the pancreas (4,8,23 (2,10).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Evidence of High Concentrations of Metallothionein in Pancreatic Hepatocytes Induced by Cadmium in Rats

et al. 1992

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The interaction of cadmium‐binding proteins (Cd‐bp) and progesterone in cadmium‐induced tissue and embryo toxicity

Wolkowski-Tyl

Preston

1979

Teratology

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Previous work indicates that a dimer of Cd-thionein (Cd-bp-D, 19,000 MW) is involved in the hereditary resistance to Cd-embryotoxicity seen in the inbred NAW/Pr (NAW) mouse strain. Cd-bp-D is not detected in virgin females after Cd exposure and is detected only after the first 24 hours of exposure to Cd in an inbred strain (C57BL/10ChPr) susceptible to Cd-induced embryotoxicity (Wolkowski, '74; Wolkowski-Tyl, '78). Since progesterone (P) is critical for maintenance of pregnancy in mice, we have studied the possible relationship between this hormone and Cd-bp-D production. As a model system, was examined effects of Cd treatment on Cd-bp synthesis in NAW males. It was anticipated that this model could provide information bearing not only on the relationship between P and Cd-bp-D production, but also on that between Cd-bp-D and Cd toxicity, since a single sc injection of CdCl2 causes typical testicular hemorrhagic necrosis in NAW males, and these animals make only metallothionein and not Cd-bp-D. NAW males were, therefore, given P (0.1 g/Kg bw) and then exposed to Cd. Sephadex gel chromatography (G-200) of liver cytosol from animals killed 24 hours later detected only Cd-bp-D. Testes of these males did not show hemorrhagic necrosis. Since the adrenals of male mammals release P in response to stress, NAW males were stressed by repeated sesame oil or propylene glycol injections (5 ml/Kg bw), or the adrenal was stimulated directly with injections of ACTH (100 IU/Kg bw) for seven days prior to Cd exposure. All methods tested which significantly elevated serum P levels (as confirmed by radioimmunoassay), also resulted in production of Cd-bp-D and absence of testicular hemorrhage in Cd-treated NAW males. Suppression of P release by injection of dexamethazone or corticosterone or by adrenalectomy resulted in testicular hemorrhage and production of only metalicthionein after Cd exposure. The relevance of the interaction between P, Cd-bp-D and protection against Cd-induced toxicity seen in the model system was supported by analysis of serum P levels in pregnant females; elevated levels were seen in resistant (NAW dams on day 10 of gestation and significantly lower levels seen in dams from a Cd-sensitive strain.

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Pancreatic metallothionein: Protection against cadmium-induced inhibition of insulin secretory activity*1

Cited by 29 publications

References 13 publications

Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and above Metal Homeostasis and Antioxidant Response

Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and above Metal Homeostasis and Antioxidant Response

Immunohistochemical Evidence of High Concentrations of Metallothionein in Pancreatic Hepatocytes Induced by Cadmium in Rats

The interaction of cadmium‐binding proteins (Cd‐bp) and progesterone in cadmium‐induced tissue and embryo toxicity

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