Non-Alcoholic Fatty Liver Disease, Diabetes Mellitus, and Zinc/ Zinc Transporters: Is there a Connection?

Abstract

Immune response and metabolic regulation are closely connected with each other in such a way that dysfunction could lead to a variety of metabolic diseases such as obesity, diabetes mellitus (Dm), lipid metabolism disorders, and fatty liver disorders. Combined with uncritical "sugar-based" overeating and malnutrition, these multisystem metabolic diseases expand into a global epidemic. There are correlations between a fatty liver disease and diabetic metabolism state. A fatty liver leads to insulin resistance and thus to the development of a type 2 Dm; insulin resistance in turn augments the fatty liver. Zinc is a trace element of fundamental importance for a variety of biological processes. The liver is the main organ of the zinc metabolism. Metallothionein and zinc transporters are the key regulators of cellular zinc homeostasis. Molecular studies support the assumption of a correlation between zinc and Dm. Zinc is essential for the synthesis, secretion, and storage of insulin. ZnT8 is a significant autoantigen for type 1 Dm. Genetic polymorphisms in the ZnT8 gene are associated with an increased risk of developing type 2 Dm. Cellular zinc restriction induces the release of stress, particularly in the endoplasmic reticulum (ER). ER stress alone or coupled with cellular stress, as well as chronic inflammation, are central to the development of insulin resistance and type 2 Dm. The present insights into the context of a non-alcoholic fatty liver disease (NAFLD) and a type 2 Dm indicate that zinc and zinc transporters at the cellular level in various forms and in interactions with other mediators both in the regulation of physiological processes and in the formation of pathological processes, such as the cellular and ER stress, as well as chronic inflammation, and the development of metabolic disorders are involved.

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

“…A haemorrhagic stroke is mainly caused by a rupture and pathological changes in small vessels. The authors consider zinc to be a modifiable risk factor for haemorrhagic stroke, particularly in relation to the incidence of zinc deficiency in obesity and type 2 diabetes mellitus [ 57 , 58 , 59 ].…”

Visual analysis of the research trend and current situation of the relationship between zinc and stroke in the past 20 years

“…The network diagram of the the cited literature is comprised of 249 nodes and 498 linkages, in addition,we run the burst detection function from the Burstness tab in the Control Panel in CiteSpace software. The results show that the keywords with higher frequency of occurrence include: oxidative stress (127), expression (78), zinc (60), activation (45), gene expression (43), cerebra ischemia (41), stroke (39), focal cerebral ischemia (39), cell death (38), ischemic stroke (36), gene (29), and risk (28) (as shown in Table 3). The keywords with the highest centrality among all are brain injury and damage, both of which are 0.27.…”

“…They [36] conducted a retrospective analysis of serum zinc de ciency in 384 patients with acute subarachnoid hemorrhage, and found that 67% (n = 257) of the patients had reduced serum zinc content in the rst 7 days after the onset of the disease. Coincidentally, Zhang et al also pointed out that zinc is a modi able risk factor for hemorrhagic stroke, especially related to the incidence of zinc de ciency in obesity and type 2 diabetes [37][38][39] . Similarly, Munhsi et al [40] reported that serum zinc concentrations were also lower in stroke patients than in healthy controls, while no signi cant differences were found in copper and iron concentrations.…”

Zinc in Liver Fibrosis

“…Moreover, zinc is important in the metabolism of neurotransmitters and growth, sex, and thyroid hormones, as well as the synthesis, secretion, and storage of insulin in the Langerhans cells of the pancreas [31]. In addition, zinc has extensive roles in both the adaptive (specific) and the innate (non-specific) immune responses at multiple steps, including gene expression as well as differentiation and development of immune cells [3,32].…”

“…There is a vicious cycle. A fatty liver contributes to insulin resistance and therefore to type 2 diabetes mellitus; insulin resistance increases the fatty liver [31,84]. NASH is defined as fatty liver with a progressive development through inflammation and typical hepatocellular damage, accompanied by pericellular fibrosis that may lead to cirrhosis [2].…”