Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs - Université de Lille Accéder directement au contenu
Article Dans Une Revue Endocrinology, Diabetes & Metabolism Année : 2023

Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs

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Introduction Nowadays, there are no strong diabetic pig models, yet they are required for various types of diabetes research. Using cutting-edge techniques, we attempted to develop a type 2 diabetic minipig model in this study by combining a partial pancreatectomy (Px) with an energetic overload administered either orally or parenterally. Methods Different groups of minipigs, including Göttingen-like (GL, n = 17) and Ossabaw (O, n = 4), were developed. Prior to and following each intervention, metabolic assessments were conducted. First, the metabolic responses of the Göttingen-like (n = 3) and Ossabaw (n = 4) strains to a 2-month High-Fat, High-Sucrose diet (HFHSD) were compared. Then, other groups of GL minipigs were established: with a single Px (n = 10), a Px combined with a 2-month HFHSD (n = 6), and long-term intraportal glucose and lipid infusions that were either preceded by a Px (n = 4) or not (n = 4). Results After the 2-month HFHSD, there was no discernible change between the GL and O minipigs. The pancreatectomized group in GL minipigs showed a significantly lower Acute Insulin Response (AIR) (18.3 ± 10.0 IU/mL after Px vs. 34.9 ± 13.7 IU/mL before, p < .0005). In both long-term intraportal infusion groups, an increase in the Insulinogenic (IGI) and Hepatic Insulin Resistance Indexes (HIRI) was found with a decrease in the AIR, especially in the pancreatectomized group (IGI: 4.2 ± 1.9 after vs. 1.5 ± 0.8 before, p < .05; HIRI (×10−5): 12.6 ± 7.9 after vs. 3.8 ± 4.3 before, p < .05; AIR: 24.4 ± 13.7 µIU/mL after vs. 43.9 ± 14.5 µIU/mL before, p < .005). Regardless of the group, there was no fasting hyperglycemia. Conclusions In this study, we used pancreatectomy followed by long-term intraportal glucose and lipid infusions to develop an original minipig model with metabolic syndrome and early signs of glucose intolerance. We reaffirm the pig's usefulness as a preclinical model for the metabolic syndrome but without the fasting hyperglycemia that characterizes diabetes mellitus.
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hal-04558743 , version 1 (25-04-2024)

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Rebecca Goutchtat, Audrey Quenon, Manon Clarisse, Nathalie Delalleau, Anaïs Coddeville, et al.. Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs. Endocrinology, Diabetes & Metabolism, 2023, Endocrinology, Diabetes & Metabolism, 6 (4), pp.e425. ⟨10.1002/edm2.425⟩. ⟨hal-04558743⟩
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