Zinc: Roles in pancreatic physiology and disease

Abstract

Zinc is an essential trace element. Deficiencies are frequently seen with gastrointestinal diseases, including chronic pancreatitis, nutritional deficiency, and reduced intestinal absorption. Additionally, reduced zinc levels have been linked to cellular changes associated with acute pancreatitis such as enhanced inflammation with increased macrophage activation and production of inflammatory cytokines such as IL-1β, impaired autophagy, and modulation of calcium homeostasis. Preliminary data suggest that zinc deficiency may lead to pancreatic injury in animal models. The purpose of this review is to explore the biologic effects of zinc deficiency that could impact pancreatic disease. MESH KEYWORDS: Malnutrition, inflammation, trace element.

Keywords: Cytokine; Pancreatitis; Zinc.

Fig. 1.. General physiological functions of zinc

(A) within different tissues and (B) on a cellular level. ROS = reactive oxygen species; ZIPs = Zrt-Irt-like proteins; ZnTs = Zinc transporters; MT = metallothioneins; MTF-1 = metal response element binding transcription factor 1; Orai1 = calcium released-activated calcium modulator 1; GPR39 = G-protein coupled receptor 39; A20 = zinc finger protein; PPAR-α = peroxisome proliferator-activated receptor α

Fig. 2.. Proposed effects of zinc-deficiency on pancreatitis responses.

(A) Model of acute pancreatitis in with normal (Sufficiency) zinc levels; (B) Potential effects of zinc depletion (Deficiency) on acinar cell pancreatitis responses. HMGB1 = High mobility group box 1 protein; nDNA = normal DNA; mtDNA = mitochondrial DNA; Hsp = heat shock protein; Ab = antibody; DAMPs = damage-associated molecular patterns; TRPV4 = transient receptor potential cation channel subfamily V Member 4; PLA2 = phospholipase A2; Piezo1 = piezo type mechanosensitive ion channel component 1; Orai1 = calcium release-activated calcium modulator 1; RER = rough endoplasmic reticulum; SER = smooth endoplasmic reticulum; Ryr = ryanodine receptor; PMCA4b = plasma membrane calcium-transporting ATPase 4; NLRP3 = NLR family pyrin domain containing 3; Zip8 = Zrt-Irt-like protein 8; GPR39 = G-protein coupled receptor 39.