Abstract
Type II Diabetes (T2DM) negatively alters baseline tendon function, including decreased range of motion and mechanical properties; however, the biological mechanisms that promote diabetic tendinopathy are unknown. To facilitate identification of therapeutic targets we developed a novel murine model of diabetic tendinopathy. Mice fed a High Fat Diet (HFD) developed diet induced obesity and T2DM and demonstrated progressive impairments in tendon gliding function and mechanical properties, relative to mice fed a Low Fat Diet (LFD). We then determined if restoration of normal metabolic function, by switching mice from HFD to LFD, was sufficient to halt the pathological changes in tendon due to obesity/T2DM. However, switching from a HFD to LFD resulted in greater impairments in tendon gliding function than mice maintained on a HFD. Mechanistically, IRβ signaling is decreased in obese/T2DM murine tendons, suggesting altered IRβ signaling as a driver of diabetic tendinopathy. However, knock-down of IRβ expression in S100a4-lineage cells (IRcKOS100a4) was not sufficient to induce diabetic tendinopathy as no impairments in tendon gliding function or mechanical properties were observed in IRcKOS100a4, relative to WT. Collectively, these data define a murine model of diabetic tendinopathy, and demonstrate that restoring normal metabolism does not slow the progression of diabetic tendinopathy.
Highlights
Type II Diabetes Mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and a decrease in sensitivity to insulin[1], and is strongly associated with obesity[2]
While several tendons can be affected by diabetic tendinopathy, including the Achilles and the supraspinatus tendons, the flexor tendons are most commonly impacted by T2DM8,9
To address the gap in knowledge surrounding the progression of diabetic tendinopathy, we defined the effects of diet induced obesity and Type II diabetes on tendon function
Summary
Type II Diabetes Mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and a decrease in sensitivity to insulin[1], and is strongly associated with obesity[2]. While it is difficult to dissect the systemic effects of Type II Diabetes from obesity, it is clear that induction of both obesity/T2DM leads to severe alterations in metabolic function resulting in a variety of pathological changes throughout the body[3]. Diabetic tendinopathy results in severe inflammation and pain in the hand and digits[10], and decreased digit range of motion (ROM)[6]. These impairments in tendon function can severely impair use of the hands, and subsequently www.nature.com/scientificreports/. Given the loss of insulin sensitivity that was observed in obese/T2DM tendons, we generated tendon-specific Insulin Receptor (IR) conditional knockout mice to determine if IR deletion in the tendon is sufficient to recapitulate the diabetic tendinopathy phenotype
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
