Aims/hypothesis
In vitro studies point to a toxic effect of high glucose and non-esterified fatty acids on beta cells. Whether elevated levels
of glucose and lipids induce beta cell loss in vivo is less clear. The domestic cat has recently been proposed as a valuable
animal model for human type 2 diabetes because feline diabetes shows several similarities with diabetes in humans, including
obesity-induced insulin resistance, impaired beta cell function, decreased number of beta cells and pancreatic amyloid deposition.
Methods
We infused healthy cats with glucose or lipids for 10 days to clamp their blood concentrations at the approximate level found
in untreated feline diabetes (glucose: 25–30 mmol/l; triacylglycerols: 3–7 mmol/l).
Results
Glucose and lipid levels were adequately targeted. Plasma non-esterified fatty acids were increased by lipid infusion 1.7-fold.
A dramatic and progressive decline of plasma insulin levels was observed in glucose-infused cats beginning after 2 days of
hyperglycaemic clamp. In contrast, plasma insulin concentration and glucose tolerance test were not affected by hyperlipidaemia.
Compared with controls, glucose-infused cats had a 50% decrease in beta cells per pancreatic area. Apoptotic islet cells and
cleaved caspase-3-positive beta cells were observed in glucose-infused cats only.
Conclusions/interpretation
Sustained hyperglycaemia but not hyperlipidaemia induces early and severe beta cell dysfunction in cats, and excess glucose
causes beta cell loss via apoptosis in vivo. Hyperglycaemic clamps in cats may provide a good model to study the pathogenesis
of glucose toxicity in beta cells.
Keywords Apoptosis - Diabetes - Feline - Glucose toxicity - Hyperglycaemia - Hyperlipidaemia