Before glucose administration, fasted MSG rats did not show any alteration in blood glucose levels, whereas they presented higher plasma insulin levels (P<0.05; Figure 2, A and C).
Fasting glucose levels were similar in all groups (Table 2); however, normoglycemia in MSG rats was maintained by hyperinsulinemia, compared to CTL (P<0.001; Table 2).
Table 3 shows that MSG rats presented reductions of 34 and 49% in the ratio of pancreas weight per BW and total pancreas area, respectively, compared to CTL rats (P<0.0001 and P<0.03).
In the present study, we hypothesized that the increased glucose-induced insulin secretion and hyperinsulinemia in MSG rats may be linked to morphofunctional alterations in the endocrine pancreas due to vagus nerve hyperactivity, since an ANS imbalance with enhanced PNS but decreased SNS action has been previously reported in MSG-induced obesity (10).
As depicted in Figure 1(c), MSG rats that were or were not treated with metformin displayed hypophagia when compared with CTR rats.
Indeed, relative to individual BW values, the VAT pad mass was 1.8-fold (P < 0.01) higher in MSG than in CTR rats, and metformin treatment in MSG rats (MSG + metformin) was able to significantly (P < 0.05 versus MSG values) reduce VAT mass, although mass values remained significantly (P < 0.05) higher than in CTR animals (Figure 2(a)).
Interestingly, metformin treatment in MSG rats resulted in a significant (P < 0.01) reduction in the expression levels of the leptin gene in their VAT pads, although values remained higher (P < 0.02) than in CTR rats.
Interestingly, metformin treatment in MSG rats was able to significantly (P < 0.05 versus MSG group-values) reduce insulinemia, its values being now similar to those displayed by CTR animals (Figure 3(a)).
MSG rats had significantly (P < 0.05 versus C rats) higher plasma insulin and triglyceride levels, despite similar glycemia (Table 2).
Concordant with this finding, liver content of protein carbonyl groups also was significantly (P < 0.05 versus C) higher in MSG rats (Table 3), whereas the local amount of GSH, a peptide highly protective against OS development, was significantly (P < 0.05 versus C) lower in MSG rats (Table 3).
The livers from MSG rats displayed a significant (P < 0.05 versus C values) increase in the mRNA levels of Il1b, Tnfa, and Pai-1 (Figures 1(a), 1(b), and 1(c), resp.), all key signals indicative of local inflammatory process.
Tissues from MSG rats displayed a robust increase (P < 0.05 versus C) in PFK2 mRNA expression and protein content (Figures 2(c) and 2(d), resp.); similarly, G6Pase mRNA expression and activity also were significantly (P < 0.05 versus C) higher in MSG tissues (Figures 2(e) and 2(f), resp.).