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Like humans, cats have a strong relationship between decreasing insulin sensitivity and the development of diabetes with obesity. However, the underlying molecular mechanisms of impaired insulin secretion and signaling in cats remain largely unknown. A total of 54 client-owned nondiabetic lean ( n = 15), overweight ( n = 15), and diabetic ( n = 24) cats were included in the study. The pancreas, liver, and skeletal muscle were quantified for mRNA and protein abundances of insulin and incretin signaling markers. Diabetic cats showed increased liver and muscle adiposity. The pancreas of diabetic cats had decreased transcript abundances of insulin, insulin receptor, insulin-receptor substrate (IRS)-1, glucose transporters (GLUT), and protein abundance of mitogen-activated protein kinase. In treated diabetics, protein abundance of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide receptors, total and phosphorylated Akt, and GLUT-1 were increased in the pancreas, whereas untreated diabetics had downregulation of markers of insulin and incretin signaling. In the muscle and liver, diabetic cats had reduced mRNA abundances of insulin receptor, IRS-1/2, and phosphatidylinositol-3-kinase, and reduced protein abundances of GLUT-4 and phosphatidylinositol-3-kinase-p85α in muscle. We demonstrate that feline diabetes is associated with ectopic lipid deposition in the liver and skeletal muscle, deficits in insulin synthesis and incretin signaling in the pancreas, and impaired insulin signaling in the muscle and liver. These findings have implications for understanding the pathophysiological mechanisms of obesity and diabetes in humans and pets.

Background: Both diabetes mellitus (DM) and obesity are common in cats. The adipokines leptin, adiponectin, resistin and omentin are thought to have important roles in human obesity and glucose homeostasis; however, their functions in the pathophysiology of feline diabetes mellitus and obesity are poorly understood. We determined whether sexual dimorphism exists for circulating concentrations of these adipokines, whether they are associated with adiposity, and whether they correlate with basic indices of insulin sensitivity in cats. Healthy, client-owned male and female cats that were either ideal weight or obese were recruited into the study. Fasting blood glucose, fructosamine, cholesterol, triglycerides, insulin and plasma concentrations of adipokines were evaluated., Results: Obese cats had greater serum concentrations of glucose and triglycerides than ideal weight cats, but fructosamine and cholesterol concentrations did not differ between groups. Body weight and body mass index were greater in male than female cats, but circulating metabolite cocentrations were similar between sexes of both the ideal weight and obese groups. Plasma concentrations of insulin and leptin were greater in obese than ideal weight cats, with reciprocal reduction in adiponectin concentrations in obese cats; there were no sex differences in these hormones. Interestingly, plasma omentin concentrations were greater in male than female cats but with no differences between obese and ideal weight states., Conclusion: Together our findings suggest that rather than gender, body weight and adiposity are more important determinants of circulating concentrations of the adipokines leptin and adiponectin. On the contrary, the adipokine omentin is not affected by body weight or adiposity but instead exhibits sexual dimorphism in cats.

Background: Dyslipidemia, dysregulated adipokine secretion and alteration in glucagon and adropin concentrations are important obesity-related factors in the pathophysiology of human Type 2 diabetes; however, their roles in the pathophysiology of feline diabetes mellitus are relatively unknown. Here, we determined the concentrations of circulating leptin, adiponectin, pro-inflammatory cytokines, glucagon, adropin, triglycerides, and cholesterol, in non-diabetic lean and overweight cats and newly diagnosed diabetic cats. Client-owned cats were recruited and assigned into 3 study groups: lean, overweight and diabetic. Fasting blood samples were analyzed in lean, overweight and diabetic cats at baseline and 4 weeks after consumption of high protein/low carbohydrate standardized diet., Results: Serum concentrations of triglycerides were greater in diabetics at baseline and were increased in both diabetic and overweight cats at 4 weeks. Plasma leptin concentrations were greater in diabetic and overweight at baseline and 4 weeks, whereas adiponectin was lower in diabetics compared to lean and overweight cats at baseline and 4 weeks. Diabetics had greater baseline plasma glucagon concentrations compared to lean, lower adropin than overweight at 4 weeks, and lower IL-12 concentrations at 4 weeks than baseline., Conclusions: Our results suggest that feline obesity and diabetes mellitus are characterized by hypertriglyceridemia and hyperleptinemia; however, diabetic cats have significantly lower adiponectin and adropin compared to overweight cats. Thus, despite having similar body condition, overweight and diabetic cats have differential circulating concentrations of adiponectin and adropin.

While pancreatitis is now recognized as a common ailment in cats, the diagnosis remains challenging due to discordant results and suboptimal sensitivity of ultrasound and specific feline pancreatic lipase (Spec fPL) assay. Pancreatitis also shares similar clinical features with pancreatic carcinoma, a rare but aggressive disease with a grave prognosis. The objective of this pilot study was to compare the plasma proteomes of normal healthy cats (n = 6), cats with pancreatitis (n = 6), and cats with pancreatic carcinoma (n = 6) in order to identify potential new biomarkers of feline pancreatic disease. After plasma protein separation by 2-dimensional gel electrophoresis, protein spots were detected by Coomassie Brilliant Blue G-250 staining and identified by mass spectrometry. Alpha-1-acid glycoprotein (AGP), apolipoprotein-A1 (Apo-A1), and apolipoprotein-A1 precursor (Pre Apo-A1) appeared to be differentially expressed, which suggests the presence of a systemic acute-phase response and alteration of lipid metabolism in cats with pancreatic disease. Future studies involving greater case numbers are needed in order to assess the utility of these proteins as potential biomarkers. More sensitive proteomic techniques may also be helpful in detecting significant but low-abundance proteins.