Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

Abstract

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined. Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein. Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P > 0.05) between subjects with normal OGTT (n = 39), impaired glucose tolerance and/or fasting glucose (n = 17), or T2D (n = 36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P < 0.001), fasting insulin (P = 0.02), glycated hemoglobin (P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.001). Follistatin was positively correlated with HOMA-IR alone (P = 0.01). Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and Bærum Cardiovascular Diabetes (ABCD) cohort study

“…It has also been related to CAD, potentially reflecting a counteracting mechanism [35], and may reflect disease severity of type 2 diabetes [17,36,37]. The present study further supports a role for activin A in diabetes and related CV events and death by showing an independent association between activin A and adverse outcome in type 2 diabetes.…”

Differential regulation of mouse pancreatic islet insulin secretion and Smad proteins by activin ligands

“…In agreement with this, acute treatment with the small-molecule inhibitor SB-431542 potentiated GSIS in wild-type mouse islets. The importance of activin signalling for glucose homeostasis in humans is underscored by recent studies indicating a positive relationship between plasma levels of activins and clinical characteristics of human type 2 diabetes [34], as well as a significant association between single-nucleotide polymorphisms in the ACVR1C gene, encoding the activin B receptor ALK7, and the incidence of this disease in humans [35].…”

Activins and Inhibins: Roles in Development, Physiology, and Disease

“…In humans, activin A levels in serum correlate with fasting glucose, fasting insulin, and glycosylated hemoglobin levels (Wu et al 2013). Loss-and gainof-function transgenic mouse models for activins, activin receptors, FSTL-3, and Smads have contributed to our understanding of activin signaling in pancreas development and the proliferation, differentiation and function of islet cells (reviewed in Wiater and Vale 2012).…”

“…Bone marrow-derived neutrophil precursors (BMNPs) express activin A at seven-fold higher levels than mononuclear cells. Tumor necrosis factor a (TNF-a) induces activin A release from BMNPs without de novo synthesis, an effect that is blocked by insulin, suggesting a possible mechanistic link to inflammatory processes in type 2 diabetes (Wu et al 2013). In contrast, through a different mechanism, LPS has no effect on BMNPs, but stimulates activin A expression and release in total bone marrow cultures (Wu et al 2013).…”