Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma.

Armin Mooranian,Hani Al-Salami,Jacqueline Chester,Thomas Foster,Bozica Kovacevic,Sanja Kojic,Corina Mihaela Ionescu,Susbin Raj Wagle,Goran Stojanovic,Edan Johnston,Daniel Walker,Momir Mikov,Melissa Jones

doi:10.3390/biomedicines10010111

Abstract

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.

Highlights

Diabetes mellitus has been reported as a major leading cause of mortality globally, and more than 380 million patients have been diagnosed with diabetes over the last few years, with prevalence rising at an alarming rate [1]
Transplanted islet grafts become damaged and eventually die in diabetic hosts due to many challenges including unwanted cell-mediated autoimmune response and upregulation of cytokine secretion such as interleukin-6, which results in graft failure, poor glycaemic control and recurrence of diabetes [6,7]
In a recent study in our laboratory, we have shown that the bile acid taurocholic acid (TCA)

Summary

Introduction

Diabetes mellitus has been reported as a major leading cause of mortality globally, and more than 380 million patients have been diagnosed with diabetes over the last few years, with prevalence rising at an alarming rate [1]. Islet transplantation has shown promising results in several clinical trials, its success and wide use in clinical settings has been hindered by challenges such as immune rejection, formation of islet amyloid, and poor revascularization of transplanted graft promptly and adequately to allow for full cell recovery and survival for immediate but long-term graft success [5]. Biomedicines 2022, 10, 111 mediators and cytokines remain major obstacles in islet delivery and transplantation, in the long term. Transplanted islet grafts become damaged and eventually die in diabetic hosts due to many challenges including unwanted cell-mediated autoimmune response and upregulation of cytokine secretion such as interleukin-6, which results in graft failure, poor glycaemic control and recurrence of diabetes [6,7]. Inflammation plays a major role in the failure of transplanted graft and islets’ death

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