Zinc Supplementation Improves Glucose Homeostasis in High Fat-Fed Mice by Enhancing Pancreatic β-Cell Function

Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and β-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl₂ (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl₂ (HFZ). Intraperitoneal glucose (ipGTT) and insulin (ipITT) tolerance, glycemia, insulinemia, HOMA-IR, and HOMA-β were determined after 15 weeks in each diet. Glucose-stimulated insulin secretion (GSIS) was investigated in isolated islets. The insulin effect on glucose uptake, metabolism, and signaling was investigated in soleus muscle. ZnCl₂ did not affect body mass or insulin sensitivity as assessed by ipITT, HOMA-IR, muscle glucose metabolism, and Akt and GSK3-β phosphorylation. However, glucose tolerance, HOMA-β, and GSIS were significantly improved by ZnCl₂ supplementation. Therefore, ZnCl₂ supplementation improves glucose homeostasis in high fat-fed mice by a mechanism that enhances β-cell function, rather than whole-body or muscle insulin sensitivity.