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.

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

The nutritional transition that the western population has undergone is increasingly associated with chronic metabolic diseases. In this work, we evaluated a diet rich in saturated fatty acids (hyperlipidic, HL) after weaning of the offspring rats submitted to maternal protein restriction on the hepatic mitochondrial bioenergetics. Wistar rats were mated and during gestation and lactation, mothers received control diets (NP, normal protein content 17%) or low protein (LP, 8% protein). After weaning, rats received either NL (normolipidic) or HL (+59% SFA) diets up to 90 days of life. It was verified that all respiratory states of hepatic mitochondria showed a reduction in the LP group submitted to the post-weaning HL diet. This group also presented greater mitochondrial swelling compared to controls, potentiated after Ca²⁺ addition and prevented in the presence of EGTA (calcium chelator) and cyclosporin A (mitochondrial permeability transition pore inhibitor). There was also an increase in liver protein oxidation and lipid peroxidation and reduction in catalase and glutathione peroxidase activities in the LP group fed HL diet after weaning. Our data suggest that adult rats subjected to maternal protein restriction were more susceptible to hepatic mitochondrial damage caused by a diet rich in saturated fatty acids post-weaning.