Irisin administration restores beta-cell functional mass in a mouse model of type 2 diabetes

Abstract

Aim: Irisin is a hormone secreted by skeletal muscle able to improve metabolic homeostasis. Serum irisin levels are reduced in type 2 diabetes (T2D), while exogenous irisin administration improves glycemic control in diabetic mice. We have previously demonstrated that irisin promotes beta-cell survival and function both in vitro and in vivo in healthy wild type mice. We have also demonstrated that irisin restores the defective glucose-stimulated insulin secretion (GSIS) and reduces apoptosis in human pancreatic islets from patients with T2D. Nevertheless, the beta-cellular effects of in vivo irisin administration to T2D mice are still unknown. Methods: C57Bl/6 mice (n = 8) were fed a high-fat diet (HFD, 60% of energy deriving from fat) for 10 weeks and then intraperitoneally injected with streptozotocin (STZ, 100 mg/kg) to induce diabetes. Four standard diet (SD)-fed mice were used as control. HFD/STZ mice were treated with 0.5 μg/g irisin (n = 4) or vehicle (n = 4), for 14 days. Fasting glycemia, insulinemia, body weight, glucose tolerance, and pancreatic islet function were assessed. Pancreatic islet architecture was also evaluated through immunofluorescence analyses. Results: Compared to SD mice, HFD/STZ mice showed higher fasting glycemia and body weight, glucose intolerance, and reduced GSIS; in addition, HFD/STZ mice showed reduced islet volume (-78%), beta-cell area (-35%), and insulin content (-60%), and increased alpha-cell area (+54%). Irisin administration significantly restored glycemia (-31%), body weight (-13%), glucose tolerance (-27%), GSIS (+23%), islet volume (+61%), beta-cell area (+34%) and alpha-cell area (-49%), and insulin content (+36%). Of note, irisin induced a 9-fold increase in beta-cell proliferation rate. Conclusions: These results show that irisin improves glycemic homeostasis and restores the functional beta-cell mass when administered in vivo to diabetic mice, probably by promoting beta-cell proliferation.

Plasma proteins identify increased number of carotid plaques and predict occurring atherosclerotic events

“…To this end we studied, by Normalized Protein eXpression (NPX) (an index of relative abundance 12 ), the plasma levels of 368 proteins from the targeted Cardio-metabolic, Inflammation, Cardiovascular II, and III panels (Olink TM ). New omics techniques can inform on vascular activation of pathway related to atherosclerosis [13][14][15] and the power of proteomics as an independent marker of carotid atherosclerosis has been still proposed, albeit in a limited number of subjects and by addressing a maximum of 82 plasma proteins linked to cardiovascular disease 16,17 . Therefore, we searched for proteins whose expressions in plasma, recapitulating biologically relevant pathways, can improve the accuracy to identify apparently healthy subjects with asymptomatic atherosclerotic disease at the carotids and if they also could predict the occurrence of clinically overt atherosclerotic stages.…”