Sustained Hyperglycemia and Hyperlipidemia in Cats: Contribution of Inflammation and Beta-Cell Loss to the Pathophysiology of Diabetes
ACVIM 2008
E. Zini1; M. Osto2; M. Franchini3; F. Guscetti4; M. Donath5; A. Perren6; P. Linscheid1; M. Bouwman7; M. Ackermann3; T.A. Lutz2; C.E. Reusch1
1Clinic for Small Animal Internal Medicine; 2Inst. of Vet. Physiol.; 3Inst. of Virol.; 4Inst. of Vet. Pathol., Vetsuisse Faculty, University of Zurich, Switzerland; 5Clinic for Endocrinol and Diabetes, University Hospital Zurich, Switzerland; 6Dept. of Pathol., Technical University of Munchen, Germany; 7Dept. of Clinical Sciences of Companion Animals, Utrecht University, The Netherlands

Feline diabetes shares many similarities to human type 2 diabetes mellitus (T2DM), including islet amyloidosis and β-cell loss. Based on cultured rodent and human islet cells, it has been demonstrated that hyperglycemia and hyperlipidemia in T2DM have a negative effect on β-cell viability. Exposure to high glucose or lipid levels induces interleukin expression in cultured pancreatic islets, followed by Fas receptor up-regulation and apoptosis of β-cells. In addition, high glucose levels upregulate islet chemokines and attract neutrophils and macrophages. Inflammatory cells may contribute to pancreatic-islet cell death in T2DM. The objective of this study was to investigate the above findings in vivo in cats.

Eleven healthy cats were infused for 10 days with glucose (n=5) or lipids (n=6) to target their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 450-540 mg/dl; triglycerides: 265-620 mg/dl). As control groups, 10 healthy cats were either infused with saline (n=5) or did not receive infusion (n=5). On day 10, blood samples and pancreatic biopsies were collected. Levels of α1-acid glycoprotein were measured in plasma samples. Isolated pancreatic islets were used to quantify mRNA transcripts of cytokines (IL-1β, IL-6, TNF-α) and chemokines (IL-8, MCP-1) by real-time PCR. In addition, mRNA transcripts of Fas receptor were measured. To quantify islet neutrophils, pancreatic sections were immunostained with insulin and myeloperoxidase. Pancreatic sections stained with amylin or insulin was used to quantify β-cells in pancreatic islets by morphometric analysis. Statistical differences between groups were determined with non parametric tests.

Compared to controls, hyperglycemic cats had a 50% reduced number of β-cells per islet surface and an increased number of neutrophils relative to β-cells. More apoptotic cells were noted in the pancreatic islets by light microscopy. In hyperlipidemic cats the number of β-cells and neutrophils did not differ from control cats. Plasma levels of α1-acid glycoprotein were increased in cats on glucose and lipid infusion. Islet quantities of cytokine, chemokines and Fas receptor transcripts were not different between groups.

Sustained hyperglycemia causes β-cell loss in pancreatic islets of healthy cats, possibly through increased apoptosis. Even though hyperglycemia and hyperlipidemia are accompanied by a systemic inflammatory response, inflammation does not seem to occur in pancreatic islets under the present experimental conditions. The increased number of neutrophils observed in the pancreatic islets of hyperglycemic cats needs to be further explored.

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Eric Zini

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