Although the contribution to anatomical illustration by Vesalius and his followers has received much attention, less credit has been given to Veslingius and particularly Fabricius. By 1600, Fabricius had amassed more than 300 paintings that together made the Tabulae Pictae, a great atlas of anatomy that was highly admired by his contemporaries. Many of his new observations were incorporated into subsequent books, including those by Casserius, Spighelius, Harvey and Veslingius. Also of importance were the Tabulae by Eustachius (1552), which, although only published in 1714, greatly influenced anatomical wax modelling. In 1742, Pope Benedict XIV established a Museum of Anatomy in Bologna, entrusting to Ercole Lelli the creation of several anatomical preparations in wax. Felice Fontana realised that the production of a large number of models by the casting method would make cadaveric specimens superfluous for anatomical teaching and in 1771 he asked the Grand Duke to fund a wax-modelling workshop in Florence as part of the Natural History Museum, later known as La Specola. Fontana engaged Giuseppe Ferrini as his first modeller and then the 19-year-old Clemente Susini who, by his death in 1814, had superintended the production of, or personally made, more than 2000 models. In 1780, the Austrian Emperor Joseph II visited La Specola and ordered a great number of models for his Josephinum museum; these were made by Fontana with the help of Clemente Susini and supervised by the anatomist Paolo Mascagni. It is, however, in Cagliari that some of Susini's greatest waxes are to be found. These were made when he was free of Fontana's influence and were based on dissections made by Francesco Antonio Boi (University of Cagliari). Their distinctive anatomical features include the emphasis given to nerves and the absence of lymphatics in the brain, a mistake made on earlier waxes. The refined technical perfection of the anatomical details demonstrates the closeness of the cooperation between Susini and Boi, whereas the expressiveness of the faces and the harmony of colours make the models of Cagliari masterpieces of figurative art.

The results indicate that diabetes affects submandibular gland structure even when glandular function appears unaltered and suggest that morphological changes reflect functional changes chiefly regarding the secretory activity.

Obesity is the result of excess energy intake relative to expenditure, however little is known about why some individuals are more prone to weight gain than others. Inbred strains of mice also vary in their susceptibility to obesity and therefore represent a valuable model to study the genetics and physiology of weight gain and its comorbidities such as type 2 diabetes. C57BL/6J mice are susceptible to obesity and insulin resistance when fed an obesogenic diet, whereas A/J mice are resistant despite increased caloric intake. Analysis of B6- and A/J-derived chromosome substitution strains and congenic strains revealed a complex genetic and physiological basis for this phenotype. To improve our understanding of the molecular mechanisms underlying susceptibility to metabolic disease we analyzed global gene expression patterns in 6C1 and 6C2 congenic strains. 6C1 is susceptible whereas 6C2 is resistant to diet-induced obesity. In addition, we demonstrate that 6C1 is glucose intolerant and insulin resistant relative to 6C2. Pathway analysis of global gene expression patterns in muscle, adipose, and liver identified expression level differences between 6C1 and 6C2 in pathways related to basal transcription factors, endocytosis, and mitochondrial oxidative phosphorylation (OxPhos). The OxPhos expression differences were subtle but evident in each complex of the electron transport chain and were associated with a marked increase in mitochondrial oxidative capacity in the livers of the obese strain 6C1 relative to the obesity-resistant strain 6C2. These data suggests the importance of hepatic mitochondrial function in the development of obesity and insulin resistance.

To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment.