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Regenerating ? cells of the pancreas - potential developments in diabetes treatment.

ABSTRACT: INTRODUCTION:The etiology of diabetes is mainly attributed to insulin deficiency due to the lack of ? cells (type 1), or to insulin resistance that eventually results in ? cell dysfunction (type 2). Therefore, an ultimate cure for diabetes requires the ability to replace the lost insulin-secreting ? cells. Strategies for regenerating ? cells are under extensive investigation. AREAS COVERED:Herein, the authors first summarize the mechanisms underlying embryonic ? cell development and spontaneous adult ? cell regeneration, which forms the basis for developing ? cell regeneration strategies. Then the rationale and progress of each ? cell regeneration strategy is reviewed. Current ? cell regeneration strategies can be classified into two main categories: in vitro ? cell regeneration using pluripotent stem cells and in vivo reprogramming of non-? cells into ? cells. Each has its own advantages and disadvantages. EXPERT OPINION:Regenerating ? cells has shown its potential as a cure for the treatment of insulin-deficient diabetes. Much progress has been made, and ? cell regeneration therapy is getting closer to a clinical reality. Nevertheless, more hurdles need to be overcome before any of the strategies suggested can be fully translated from bench to bedside.

SUBMITTER: Dong S

PROVIDER: S-EPMC6135091 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Regenerating β cells of the pancreas - potential developments in diabetes treatment.

Dong Shengli S Wu Hongju H

Expert opinion on biological therapy 20171113 2

<h4>Introduction</h4>The etiology of diabetes is mainly attributed to insulin deficiency due to the lack of β cells (type 1), or to insulin resistance that eventually results in β cell dysfunction (type 2). Therefore, an ultimate cure for diabetes requires the ability to replace the lost insulin-secreting β cells. Strategies for regenerating β cells are under extensive investigation.<h4>Areas covered</h4>Herein, the authors first summarize the mechanisms underlying embryonic β cell development a ...[more]

PMID: 29130349

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Project description:ObjectiveTo evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, Cochrane Library, and grey literature up to 2 February 2018.Eligibility criteria for selecting studiesRandomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality.Results40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (-8.52%, -11.14% to -5.9%) or below 3.9 mmol/L (-1.49%, -1.86% to -1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems.ConclusionsArtificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.

Project description:Regenerating (REG) proteins are associated with islet development, β-cell damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are involved in cell growth/survival and/or inflammation and the Reg1 promoter contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2 diabetes, overexpress Reg1, 3α, 3β and 3γ, vs Wistar islets. Goto-Kakizaki rat islets also exhibit increased cytokine/chemokine expression/release, particularly IL-6. Here we analyzed Reg1 and Reg3β expression and REG-1 immuno-localization in the GK rat pancreas in relationship with inflammation. Isolated pancreatic islets and acinar tissue from male adult Wistar and diabetic GK rats were used for quantitative RT-PCR analysis. REG-1 immunohistochemistry was performed on paraffin sections with a monoclonal anti-rat REG-1 antibody. Islet cytokine/chemokine release was measured after 48 h-culture. Islet macrophage-positive area was quantified on cryostat sections using anti-CD68 and major histocompatibility complex (MHC) class II antibodies. Pancreatic exocrine-to-endocrine Reg1 and Reg3β mRNA ratios were markedly increased in Wistar vs GK rats. Conversely, both genes were upregulated in isolated GK rat islets. These findings were unexpected, because Reg genes are expressed in the pancreatic acinar tissue. However, we observed REG-1 protein labeling in acinar peri-ductal tissue close to islets and around large, often disorganized, GK rat islets, which may retain acinar cells due to their irregular shape. These large islets also showed peri-islet macrophage infiltration and increased release of various cytokines/chemokines, particularly IL-6. Thus, IL-6 might potentially trigger acinar REG-1 expression and secretion in the vicinity of large diabetic GK rat islets. This increased acinar REG-1 expression might reflect an adaptive though unsuccessful response to deleterious microenvironment.

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Regenerating ? cells of the pancreas - potential developments in diabetes treatment.

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Regenerating β cells of the pancreas - potential developments in diabetes treatment.

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