Vagotomy did not alter insulin secretion at 16.7 mM glucose in Mvag rats (Figure 3A) compared to MSG rats. However, a reduction in glucose-induced insulin secretion in islets from MSG rats submitted to early subdiaphragmatic vagotomy has been reported previously (16).
Our results indicated that the PNS was chronically involved in endocrine pancreas modification in obesity of MSG rats because, after 2 months of subdiaphragmatic vagotomy, Mvag rats exhibited normal values for pancreas weight and area, percentage of total islet and [beta]-cell areas (Table 3), [beta]-cell number per [beta]-cell area, and [beta]-cell size (Figure 6).
Our study, in addition to detecting morphofunctional alterations in the pancreas of MSG rats, also replicated the obesity parameters that have been previously reported for MSG rats (13-15,17,30), since MSG rats presented lower values for BW and nasoanal length and increased values for Lee index and fat deposition, normoglycemia, hyperinsulinemia, dyslipidemia, glucose intolerance, and insulin resistance (Tables 1 and 2; Figures 1 and 2).
In conclusion, we demonstrated for the first time that hyperinsulinemia and insulin hypersecretion in response to glucose in MSG rats was associated with an increase in [beta]-cell number promoted by PNS action in pancreatic islets.
Conversely, in MSG rats, plasma lipid levels were already significantly (P < 0.05 versus respective time 0 values) higher than the 2h after LPS, and this effect lasted until the end of the experimental design (4h).
The analysis of our animals' phenotypes indicated that, although all MSG rats remained hypophagic, their overall stunted growth (growing curve, low body weight, and large adiposity) was significantly ameliorated by metformin treatment.
In this regard, the adiposity dysfunction, namely that developed at the VAT level, in MSG rats was highly improved by the oral treatment of animals with a very low dose of metformin.
We found that our MSG rats are dyslipidemic, tallying with the stimulated liver lipogenic process revealed by elevated expression levels of their master regulator gene, Srebp1c, as well as their target genes, Fas and Gpat .
It should be considered that, within an insulin-resistant state scenario, we were able to determine that, in chronic hypercorticosteronemic MSG rats, similarly to that previously found in Cushing's patients , the liver high activity of the two key enzymes, GCK and G6Pase, assures (within a very active futile cycle) a drastic increase of high glucose liver content.
Additionally, as mentioned above, we noticed that FK protein and activity were drastically augmented and reduced, respectively, in livers from MSG rats. It must be borne in mind that the liver lipid metabolism in MSG rats is clearly displaced to enhanced lipogenesis; thus it could be speculated that, in the postprandial condition any further liver entry of hexoses, through FK downstream reactions, could result in dramatic local lipid overproduction because carbons enter through this pathway bypass glycolysis regulatory steps and are then used in the lipogenic process in a direct and an uncontrolled fashion [45-47].