{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:17:25Z","timestamp":1776964645538,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:00:00Z","timestamp":1733616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Calgary Clinical Research Fund"},{"name":"Western College of Veterinary Medicine Research Fund"},{"name":"Texas Tech University School of Veterinary Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-p85\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms252313195","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:01:37Z","timestamp":1733716897000},"page":"13195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues"],"prefix":"10.3390","volume":"25","author":[{"given":"Souvik","family":"Patra","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, 7671 Evans Drive, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal J.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth R.","family":"Snead","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Warren","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Cosford","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7300-2918","authenticated-orcid":false,"given":"Prasanth K.","family":"Chelikani","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, 7671 Evans Drive, Amarillo, TX 79106, USA"},{"name":"Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41574-023-00818-3","article-title":"Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus","volume":"19","author":"Lutz","year":"2023","journal-title":"Nat. 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