**2. Concluding remarks**

on the scope of zinc deficit in the serum [28]. Zinc supplementation improved in patients with liver cirrhosis and hepatic encephalopathy with and without Dm neurologic symptoms and signs of malnutrition [62–64]. Zinc administration increased glucose disposal entirely due to noninsulin-mediated glucose uptake without any systematic effect on insulin secretion and sensitivity [65]. Ruz et al. [58] recommended to further determine the role of zinc in type 2 Dm and therapeutic effectiveness of supplementation by long-term studies under observation of factors such as stage of disease, comorbidities, that is, also NAFLD, duration and type of medication (zinc preparation), and, finally, also examining the genetic variations in SLC30A8 as well due to the heterogeneity and complexity with multiple influences on the

**Figure 1.** Schematic illustration of the organs, cells, substrates and main mediators involved in the development of

insulin resistance linking NAFLD and type 2 Dm.

disease (**Figure 1**).

48 Liver Research and Clinical Management

The data and findings that are available to date, and certainly not comprehensive, on the interrelation of fatty liver disease and type 2 diabetes mellitus show that zinc and zinc transporters on a cellular level are involved in the regulation of physiological processes as well as the development of pathological processes such as cellular stress, ER stress and not least chronic inflammation in diverse manners and interactions with other mediators, and therefore also in the development of such metabolic diseases.

Due to high complexity of the diseases, there are no simple solutions, that is, normalization of one "pathway" is not enough to recover functional homeostasis (controlling the diseases, health) of the integrated processes. Sole zinc substitution is surely ineffective in most cases, but may promise success in combination with other substrates.
