The relationship between beta cell activation and SLC30A8/ZnT8 levels of the endocrine pancreas and maternal zinc deficiency in rats

Zinc is found in very high concentrations in pancreatic tissue, particularly in insulin-secreting β cells [1]. Since zinc is secreted togetherThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. with the hormone insulin, the high zinc concentration in β cells is therefore located in the insulin secretory granules [2]. As insulin is released into the environment, the insulin crystal is broken down into monomeric insulin and free zinc. Free zinc can be reabsorbed into β cells and affect insulin secretion [1], [2]. Therefore, zinc is a critical element in the endocrine function of the pancreas.

Zinc makes critical contributions to the mechanism of action of insulin: 1. Zinc stimulates the phosphorylation of the beta subunit of the insulin receptor [3]. 2. Zinc also shows insulin-like effects by causing inhibition of GSK-3β [4], [5]. This situation makes zinc a treatment option for diabetes mellitus or insulin resistance. 3. Another molecule that zinc affects in the insulin signaling pathway is insulin-responsive aminopeptidase (IRAP) [5]. IRAP activity, which is necessary for the maintenance of glucose transporter 4 (GLUT4) levels, requires zinc. This indicates the effects of zinc on the insulin signaling pathway.

The endocrine function of pancreatic β-cells is closely related to the tight regulation of zinc [6]. Although the processing and storage of insulin are provided by zinc, it should be kept in mind that high zinc levels cause toxic effects [7]. ZnT8, a zinc transporter protein encoded by SLC30A8 gene, plays a critical role in pancreatic β-cell regulation of zinc regulation [7]. Because of these effects, ZnT8 is also associated with the pathogenesis of diabetes [8].

In conclusion, SLC30A8/ZnT8 is a carrier protein primarily responsible for the transport of zinc to granules in β-cells. Consistent with this task, ZnT8 is mainly expressed in β-cells of the pancreas. However, albeit at very low levels, SLC30A8 mRNA and ZnT8 protein are found in the α-cells of the pancreas [2], [9].

In the current study, in infant male rats born to mothers fed a zinc-deficient diet will be fed a zinc-deficient and/or zinc-fortified diet for 45 days after weaning. The aim of this study was to investigate how dietary zinc status affects pancreatic beta cell activation and ZnT8 levels in infant male rats born to zinc-deficient mothers.

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