Decreased gene expression of insulin signaling genes in insulin sensitive tissues of obese cats

Abstract

Type 2 diabetes mellitus (DM) animal models have provided ample opportunity for investigating pathogenesis, as well as to evaluate novel treatment and prevention options for the disease. Because the domestic cat shares a similar environment with humans, it is also confronted with many similar risk factors for diabetes, such as physical inactivity and obesity. Obesity is a significant risk factor for diabetes in cats, and as such, the domestic cat may serve as an ideal model for investigating obesity induced insulin resistance. This study determined changes in insulin signaling genes within insulin sensitive tissues of obese felines. Quantitative RT-PCR was performed to determine mRNA levels of three important insulin signaling genes which have been implicated with insulin resistance: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3'-kinase (PI3-K) p85alpha. Obese cats had significantly lower IRS-2 and PI3-K p85alpha mRNA levels in liver and skeletal muscle as compared to control cats. This down regulation of insulin signaling genes in obese cats mirrors that of obese humans and rodents suffering from insulin resistance. Interestingly, preprandial blood tests indicated that our obese cats were no different from control cats with regards to glucose tolerance and insulin resistance, thus indicating that the obese cats used in our study had a moderate level of obesity. Therefore, insulin signaling gene alterations were occurring in insulin sensitive tissues of moderately obese felines before glucose intolerance was clinically evident. As such, the monitoring of key insulin signaling genes may have some important diagnostic value to determine the risk level and degree of obesity induced insulin resistance.

ANIMAL MODELS OF DISEASE: Classification and etiology of diabetes in dogs and cats

“…In cats that became obese, the expression of the insulin-sensitive glucose transporter GLUT4 (SLC2A4) in muscle and fat was significantly lower than that in lean cats, whereas the expression of GLUT1 (SLC2A1), which is not insulin sensitive, remained unchanged (Brennan et al 2004). Expression of several insulin signaling genes in liver and skeletal muscles was significantly lower in obese cats than in lean cats, which is similar in humans with insulin resistance (Mori et al 2009). Also similar to humans, it is now recognized in cats that adipose tissue is an active and complex endocrine organ.…”

Potential use of cholesterol lipoprotein profile to confirm obesity status in dogs

“…In conclusion, aberrations to sub HDL-Cho fractions might serve as potential indicator for confirming obesity status in conjunction with BCS, in clinically healthy animals exhibiting no overt signs of obesity, since lipoprotein profiles reflect the lipid metabolism state in animals (Hisao et al 2007;Mori et al 2009). A decrease in HDL2 and 3-Cho fraction % accompanied by either an increase in HDL1-Cho fraction % in females or an increase in VLDL and LDL-Cho fraction % in males was observed in BCS determined older (≥8 years old) obese dogs which were otherwise diagnosed to be clinically healthy, according to their anamnesis and based on clinical signs by veterinarians.…”

Spontaneous Diabetes Mellitus in Animals

“…In addition, three important insulin signaling genes are downregulated in liver and muscle of the moderate obese cats: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3'-kinase (PI3-K) p85alpha. These data add a new resemblance between human and feline insulin resistance specific for NIDDM [93].…”