The use of animal models in diabetes research requires reliable tests for evaluation of insulin sensitivity and β-cell function. Minipigs are being increasingly used in metabolic research, and the aim of this study was to compare different tests and indexes for evaluation of insulin sensitivity and β-cell function in Göttingen minipigs. Hyperinsulinemic, isoglycemic clamp, intravenous (IVGTT) and oral glucose tolerance tests (OGTT), and a modified insulin tolerance test were performed in minipigs fed either low- or high-energy diet. Furthermore, the reproducibility of IVGTT-derived parameters was assessed. Previously described insulin sensitivity indexes [steady-state glucose infusion rate/glucose concentration/insulin concentration from clamp (M/G/I); oral glucose insulin sensitivity (OGIS) and ISIcomp from OGTT; SI from minimal model analysis of IVGTT; and quantitative insulin sensitivity check index from fasting values] were calculated together with an insulin sensitivity index from the modified insulin tolerance test (ISIITT) and a new simple index (S2) derived from the first 30 min of the IVGTT. β-Cell function was assessed from the IVGTT and the OGTT. Reproducibility of the IVGTT-derived parameters was calculated as median intraindividual coefficient of variation (CV%).M/G/I correlated significantly only with S2 ( P < 0.05, r = 0.54). S2 furthermore correlated with SI ( P < 0.001, r = 0.81), ISIITT ( P < 0.001, r = 0.57), and the two indexes from OGTT, ISIcomp ( P < 0.001, r = 0.78) and OGIS ( p < 0.05, r = 0.48). No correlation was found between β-cell function indexes from OGTT and IVGTT. The median CV% of the new S2 index was 13. In conclusion, the new simple index of insulin sensitivity, S2, was revealed to be useful for evaluation of insulin sensitivity in pigs.

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Aims The aim of this study was to assess the effect of FGF21 on food intake, body weight, body composition, glucose homeostasis, bone mineral density (BMD), cortisol and growth hormone (GH) in obese minipigs. The pig is a unique model for studying FGF21 pharmacology as it does not express UCP1, unlike mice and humans. Methods Twelve obese Göttingen minipigs with a mean body weight of 91.6 ± 6.7 kg (mean ± SD) received subcutaneously either vehicle (n = 6) or recombinant human FGF21 (n = 6) once daily for 14 weeks (0.1 mg/kg for 9.5 weeks and 0.3 mg/kg for 4.5 weeks). Results Treatment of obese minipigs with FGF21 led to a 50% reduction in food intake and a body weight loss of, on average, 18 kg compared to the vehicle group after 14 weeks of dosing. Glucose tolerance and insulin sensitivity, evaluated by intravenous glucose tolerance test, were significantly improved in the FGF21 group compared to the vehicle group at the end of the study. The plasma cortisol profile was unaffected by FGF21, whereas a small decrease in peak GH values was observed in the FGF21‐treated animals after 7 to 9.5 weeks of treatment compared to the vehicle group. Whole‐body BMD was not affected by 13 weeks of FGF21 dosing. Conclusion Despite a lack of UCP‐1 in obese minipigs, FGF21 treatment induced a significant weight loss, primarily a result of reduction in food intake, with no adverse effect on BMD or plasma cortisol.

BackgroundAdult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development.New methodIn this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia.ResultsLesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery.Comparison with existing methodsCompared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates.ConclusionThe lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs.