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Review
. 2016:2016:2846570.
doi: 10.1155/2016/2846570. Epub 2016 Oct 23.

Considerations for Defining Cytokine Dose, Duration, and Milieu That Are Appropriate for Modeling Chronic Low-Grade Inflammation in Type 2 Diabetes

Craig S Nunemaker  1
Affiliations
Review

Considerations for Defining Cytokine Dose, Duration, and Milieu That Are Appropriate for Modeling Chronic Low-Grade Inflammation in Type 2 Diabetes

Craig S Nunemaker. J Diabetes Res. 2016.

Abstract

Proinflammatory cytokines have been implicated in the pathophysiology of both type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D is an autoimmune disease involving the adaptive immune system responding to pancreatic beta-cells as antigen-presenting cells. This attracts immune cells that surround pancreatic islets (insulitis) and secrete cytokines, such as IL-1beta, IFN-gamma, and TNF-alpha, in close proximity to pancreatic beta-cells. In contrast, there is little evidence for such a focused autoimmune response in T2D. Instead, the innate immune system, which responds to cellular damage and pathogens, appears to play a key role. There are three major sources of proinflammatory cytokines that may impact islet/beta-cell function in T2D: (1) from islet cells, (2) from increased numbers of intraislet macrophages/immune cells, and (3) from increased circulating levels of proinflammatory cytokines due to obesity, presumably coming from inflamed adipose tissue. These differences between T1D and T2D are reflected by significant differences in the cytokine concentration, duration, and milieu. This review focuses on chronic versus acute cytokine action, cytokine concentrations, and cytokine milieu from the perspective of the pancreatic islet in T2D. We conclude that new cytokine models may be needed to reflect the pathophysiology of T2D more effectively than what are currently employed.

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Figures

Figure 1
Figure 1
A flowchart of very basic differences in the pathophysiology of T1D and T2D. Each disease is described by the immune-mediated triggers, processes, and results with respect to the pancreatic beta-cell/islet.
Figure 2
Figure 2
Islet viability and function following overnight treatment with different cytokine concentrations. (a) Cell death measurements by propidium iodide (PI) were made on islets following treatment with Roswell Park Memorial Institute 1640 media (untreated), 10 pg/mL IL-1beta + 20 pg/mL TNF-alpha + 200 pg/mL IFN-gamma (T2D-like), or 500 pg/mL IL-1beta + 1000 pg/mL TNF-alpha + 10,000 pg/mL IFN-gamma (T1D-like). (b) Glucose-stimulated insulin secretion (GSIS) in 3 mM glucose (3G, open bars) and 28 mM glucose (28G, filled bars) following cytokine treatments listed in (a). ∗ P value < 0.05.
Figure 3
Figure 3
A basic depiction of the putative sources of cytokines affecting islets in T2D.
See this image and copyright information in PMC

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