Patra Souvik, McMillan Chantal J, Snead Elisabeth R, Warren Amy L, Cosford Kevin, Chelikani Prasanth K
School of Veterinary Medicine, Texas Tech University, 7671 Evans Drive, Amarillo, TX 79106, USA.
Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada.
Int J Mol Sci. 2024 Dec 8;25(23):13195. doi: 10.3390/ijms252313195.
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 ( = 15), overweight ( = 15), and diabetic ( = 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.
与人类一样，猫在胰岛素敏感性降低与肥胖相关的糖尿病发展之间存在密切关系。然而，猫胰岛素分泌和信号传导受损的潜在分子机制在很大程度上仍不清楚。该研究共纳入了54只客户拥有的非糖尿病瘦猫（n = 15）、超重猫（n = 15）和糖尿病猫（n = 24）。对胰腺、肝脏和骨骼肌进行了胰岛素和肠促胰岛素信号标志物的mRNA和蛋白质丰度定量分析。糖尿病猫的肝脏和肌肉脂肪含量增加。糖尿病猫的胰腺中胰岛素、胰岛素受体、胰岛素受体底物（IRS）-1、葡萄糖转运蛋白（GLUT）的转录本丰度降低，丝裂原活化蛋白激酶的蛋白质丰度也降低。在接受治疗的糖尿病猫中，胰腺中胰高血糖素样肽-1和葡萄糖依赖性促胰岛素多肽受体、总Akt和磷酸化Akt以及GLUT-1的蛋白质丰度增加，而未治疗的糖尿病猫胰岛素和肠促胰岛素信号标志物下调。在肌肉和肝脏中，糖尿病猫胰岛素受体、IRS-1/2和磷脂酰肌醇-3-激酶的mRNA丰度降低，肌肉中GLUT-4和磷脂酰肌醇-3-激酶-p85α的蛋白质丰度降低。我们证明，猫糖尿病与肝脏和骨骼肌中的异位脂质沉积、胰腺中胰岛素合成和肠促胰岛素信号传导缺陷以及肌肉和肝脏中胰岛素信号传导受损有关。这些发现对于理解人类和宠物肥胖及糖尿病的病理生理机制具有重要意义。
