Comprehensive Physiology Wiley Online Library

Pancreatic Islets as a Target of Adipokines

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Rising rates of obesity are intricately tied to the type 2 diabetes epidemic. The adipose tissues can play a central role in protection against or triggering metabolic diseases through the secretion of adipokines. Many adipokines may improve peripheral insulin sensitivity through a variety of mechanisms, thereby indirectly reducing the strain on beta cells and thus improving their viability and functionality. Such effects will not be the focus of this article. Rather, we will focus on adipocyte‐secreted molecules that have a direct effect on pancreatic islets. By their nature, adipokines represent potential druggable targets that can reach the islets and improve beta‐cell function or preserve beta cells in the face of metabolic stress. © 2022 American Physiological Society. Compr Physiol 12: 4039–4065, 2022.

Figure 1. Figure 1. Relative levels of adipokines in the lean and obese states and their effects on pancreatic beta cells. Well‐regulated adipokine levels, as found in lean adipose tissue, are key for the maintenance of healthy beta‐cell function. Under conditions of obesity and type 2 diabetes mellitus, adipokine levels are significantly altered due to metabolic stress and adipocyte dysfunction. The subsequent dysregulated secretion of adipokines negatively impacts beta‐cell function. Obese adipose tissue produces higher levels of prodiabetic adipokines (such as RBP4 and resistin), which impairs glucose‐stimulated insulin secretion from beta cells. On the other hand, the production of antidiabetic adipokines like adipsin and adiponectin, which promote insulin secretion and beta‐cell health, is reduced. Adipsin is increased in obesity but reduced in people with type 2 diabetes and patients with beta‐cell failure. Thus, regulated adipokine secretion is crucial to the maintenance of pancreatic beta‐cell function and mass.
Figure 2. Figure 2. Source of adipokines available to pancreatic islets. Putative adipokines are frequently secreted by a number of cell types in addition to adipocytes. Therefore, a considerable proportion of these factors available to pancreatic islets may not be adipose‐derived. In many cases, pancreatic islets themselves can be a significant source, suggesting a predominantly autocrine or paracrine role (e.g., RBP4). Additionally, some adipocyte‐secreted factors remain within the adipose tissue and do not enter the circulation, making them unavailable to pancreatic islets (e.g., FGF21). “Adipose Tissue” includes all fat depots except peripancreatic fat which is listed separately 38, “Pancreatic Islets” denotes expression by any cell type within the islet 199, and “Other Tissues” denotes expression in any tissue other than the ones listed before 316. “n/a” indicates that the expression of a factor in a given tissue has not been assessed, whereas “/” indicates that expression has been assessed and was found to be absent.

Figure 1. Relative levels of adipokines in the lean and obese states and their effects on pancreatic beta cells. Well‐regulated adipokine levels, as found in lean adipose tissue, are key for the maintenance of healthy beta‐cell function. Under conditions of obesity and type 2 diabetes mellitus, adipokine levels are significantly altered due to metabolic stress and adipocyte dysfunction. The subsequent dysregulated secretion of adipokines negatively impacts beta‐cell function. Obese adipose tissue produces higher levels of prodiabetic adipokines (such as RBP4 and resistin), which impairs glucose‐stimulated insulin secretion from beta cells. On the other hand, the production of antidiabetic adipokines like adipsin and adiponectin, which promote insulin secretion and beta‐cell health, is reduced. Adipsin is increased in obesity but reduced in people with type 2 diabetes and patients with beta‐cell failure. Thus, regulated adipokine secretion is crucial to the maintenance of pancreatic beta‐cell function and mass.

Figure 2. Source of adipokines available to pancreatic islets. Putative adipokines are frequently secreted by a number of cell types in addition to adipocytes. Therefore, a considerable proportion of these factors available to pancreatic islets may not be adipose‐derived. In many cases, pancreatic islets themselves can be a significant source, suggesting a predominantly autocrine or paracrine role (e.g., RBP4). Additionally, some adipocyte‐secreted factors remain within the adipose tissue and do not enter the circulation, making them unavailable to pancreatic islets (e.g., FGF21). “Adipose Tissue” includes all fat depots except peripancreatic fat which is listed separately 38, “Pancreatic Islets” denotes expression by any cell type within the islet 199, and “Other Tissues” denotes expression in any tissue other than the ones listed before 316. “n/a” indicates that the expression of a factor in a given tissue has not been assessed, whereas “/” indicates that expression has been assessed and was found to be absent.
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Moritz Reiterer, Ankit Gilani, James C. Lo. Pancreatic Islets as a Target of Adipokines. Compr Physiol 2022, 12: 4039-4065. doi: 10.1002/cphy.c210044