Plasma Gelsolin Levels Decrease in Diabetic State and Increase upon Treatment with F-Actin Depolymerizing Versions of Gelsolin

Abstract

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care.

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

“…rhuGSN is a recombinant form of pGSN having a similar structure and function as pGSN [18]. It is well established that the level of pGSN declines in a variety of ailments such as inflammation, diabetes, trauma, sepsis, rheumatoid arthritis, and multiple sclerosis [15,16,21,31], and exogenous rhuGSN supplement/replacement therapy effectively rescues the affected animals from inflammation [15,32], sepsis [9,22], burn [33], diabetes [16], and thrombosis and pulmonary thromboembolism [17].…”

“…Plasma gelsolin (pGSN) thus plays a critical role in severing and clearing actin filaments released into the bloodstream after any tissue injury [14]. In addition, gelsolin levels have been stated to decline in a plethora of diseases, and supplementing exogenous recombinant human gelsolin (rhuGSN) alleviated distress symptoms in many disease conditions including sepsis, inflammation, diabetes [15,16], thrombosis, and pulmonary thromboembolism [17]. Interestingly, cytoplasmic gelsolin (cGSN) can bind to globular actin to nucleate its polymerization and surprisingly can also bind to filamentous actin to break and cap it back to monomeric actin form [12,18,19].…”

The effects of leptin on F-actin remodelling in type 1 diabetes

“…It was suggested that a high plasma glucose level could induce actin cytoskeleton disruption [22]. This is asserted to relate apoptotic cell death [25]. That is why F-actin could release from cell to plasma when cell injury is occurred [10].…”

Proteomic and structural heart changes in obese rats are incompletely restored after weight loss

“…Apolipoprotein A1 and APOC3 levels were elevated in the heart, but they are expressed in the liver and intestine and apparently their cardiac accumulation accompanied the influx of lipids and cholesterol to the heart [59][60][61]. Decreased levels of gelsoline indicates pathological conditions as this protein normally occurs in high amounts and is extensively degraded when binding to filamentous actin (released upon cell death or rupture) occurs [62]. This protein mitigates the detrimental effects of systemic inflammation [63], thus gelsoline downregulation could potentiate a greater impact of obesity-related inflammation on the system.…”