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Open AccessEditorial

The Pancreatic Beta Cell: Editorial

by Alberto Bartolomé

Biomolecules 2023, 13(3), 495; https://doi.org/10.3390/biom13030495 - 08 Mar 2023

Cited by 5 | Viewed by 1665

Abstract

Pancreatic beta cells play a critical role in maintaining glucose homeostasis by serving as the primary source of insulin [...] Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

Research

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13 pages, 2137 KiB

Open AccessEditor’s ChoiceArticle

Gene Delivery of Manf to Beta-Cells of the Pancreatic Islets Protects NOD Mice from Type 1 Diabetes Development

by Kailash Singh, Orian Bricard, Jeason Haughton, Mikaela Björkqvist, Moa Thorstensson, Zhengkang Luo, Loriana Mascali, Emanuela Pasciuto, Chantal Mathieu, James Dooley and Adrian Liston

Biomolecules 2022, 12(10), 1493; https://doi.org/10.3390/biom12101493 - 16 Oct 2022

Cited by 4 | Viewed by 4313

Abstract

In type 1 diabetes, dysfunctional glucose regulation occurs due to the death of insulin-producing beta-cells in the pancreatic islets. Initiation of this process is caused by the inheritance of an adaptive immune system that is predisposed to responding to beta-cell antigens, most notably [...] Read more.

In type 1 diabetes, dysfunctional glucose regulation occurs due to the death of insulin-producing beta-cells in the pancreatic islets. Initiation of this process is caused by the inheritance of an adaptive immune system that is predisposed to responding to beta-cell antigens, most notably to insulin itself, coupled with unknown environmental insults priming the autoimmune reaction. While autoimmunity is a primary driver in beta-cell death, there is growing evidence that cellular stress participates in the loss of beta-cells. In the beta-cell fragility model, partial loss of islet mass requires compensatory upregulation of insulin production in the remaining islets, driving a cellular stress capable of triggering apoptosis in the remaining cells. The Glis3-Manf axis has been identified as being pivotal to the relative fragility or robustness of stressed islets, potentially operating in both type 1 and type 2 diabetes. Here, we have used an AAV-based gene delivery system to enhance the expression of the anti-apoptotic protein Manf in the beta-cells of NOD mice. Gene delivery substantially lowered the rate of diabetes development in treated mice. Manf-treated mice demonstrated minimal insulitis and superior preservation of insulin production. Our results demonstrating the therapeutic potential of Manf delivery to enhance beta-cell robustness and avert clinical diabetes. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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16 pages, 3343 KiB

Open AccessArticle

4-OI Protects MIN6 Cells from Oxidative Stress Injury by Reducing LDHA-Mediated ROS Generation

by Jianmin Wu, Xingshi Gu, Juan Zhang, Ze Mi, Zhenhu He, Yuqian Dong, Wu Ge, Kedar Ghimire, Pengfei Rong, Wei Wang and Xiaoqian Ma

Biomolecules 2022, 12(9), 1236; https://doi.org/10.3390/biom12091236 - 04 Sep 2022

Cited by 5 | Viewed by 2922

Abstract

Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic [...] Read more.

Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic acid cycle, has both anti-inflammatory and antioxidant properties. The effects of itaconate on beta cells under oxidative stress are relatively unknown. We explored the effects of 4-octyl itaconate—a cell-permeable derivative of itaconate—on MIN6 (a beta cell model) under oxidative stress conditions caused by hypoxia, along with its mechanism of action. Treatment with 4-OI reversed hypoxia-induced cell death, reduced ROS production, and inhibited cell death pathway activation and inflammatory cytokine secretion in MIN6 cells. The 4-OI treatment also suppressed lactate dehydrogenase A (LDHA)activity, which increases under hypoxia. Treatment of cells with the ROS scavenger NAC and LDHA-specific inhibitor FX-11 reproduced the beneficial effects of 4-OI on MIN6 cell viability under oxidative stress conditions, confirming its role in regulating ROS production. Conversely, overexpression of LDHA reduced the beneficial effects exerted by 4-OI on cells. Our findings provide a strong rationale for using 4-OI to prevent the death of MIN6 cells under oxidative stress. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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9 pages, 1482 KiB

Open AccessArticle

The Glucose Sensitivity of Insulin Secretion-Lessons from In Vivo and In Vitro Studies in Mice

by Bo Ahrén

Biomolecules 2022, 12(7), 976; https://doi.org/10.3390/biom12070976 - 12 Jul 2022

Cited by 2 | Viewed by 1456

Abstract

This study explored the relationship between the glucose dose and insulin response from beta cells in vivo and in vitro in mice. Glucose was administered intravenously at different dose levels (from 0 to 0.75 g/kg) in anesthetized C57BL/6J mice, and the glucose and [...] Read more.

This study explored the relationship between the glucose dose and insulin response from beta cells in vivo and in vitro in mice. Glucose was administered intravenously at different dose levels (from 0 to 0.75 g/kg) in anesthetized C57BL/6J mice, and the glucose and insulin concentrations were determined in samples taken after 50 min. Furthermore, freshly isolated mouse islets were incubated for 60 min in the presence of different concentrations of glucose (from 2.8 to 22.2 mmol/L) and insulin levels were analyzed in the medium. It was found that insulin levels increased after an intravenous injection of glucose with the maximal increase seen after 0.35 g/kg with no further increase after 0.5 or 0.75 g/kg. The acute increase in insulin levels (during the first 5 min) and the maximum glucose level (achieved after 1 min) showed a curvilinear relation with the half-maximal increase in insulin levels achieved at 11.4 mmol/L glucose and the maximal increase in insulin levels at 22.0 mmol/L glucose. In vitro, there was also a curvilinear relation between glucose concentrations and insulin secretion. Half maximal increase in insulin concentrations was achieved at 12.5 mmol/L glucose and the maximal increase in insulin concentrations was achieved at 21.5 mmol/L. Based on these data, we concluded that the glucose-insulin relation was curvilinear both in vivo and in vitro in mice with similar characteristics in relation to which glucose levels that achieve half-maximal and maximal increases in insulin secretion. Besides the new knowledge of knowing these relations, the results have consequences on how to design studies on insulin secretion to obtain the most information. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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10 pages, 3245 KiB

Open AccessArticle

Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro

by Katelyn Millette, Keith Rodriguez, Xia Sheng, Stacey D. Finley and Senta Georgia

Biomolecules 2022, 12(2), 215; https://doi.org/10.3390/biom12020215 - 26 Jan 2022

Cited by 3 | Viewed by 2546

Abstract

As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell [...] Read more.

As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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20 pages, 3249 KiB

Open AccessArticle

Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

by Emily S. Krueger, Joseph L. Beales, Kacie B. Russon, Weston S. Elison, Jordan R. Davis, Jackson M. Hansen, Andrew P. Neilson, Jason M. Hansen and Jeffery S. Tessem

Biomolecules 2021, 11(12), 1892; https://doi.org/10.3390/biom11121892 - 17 Dec 2021

Cited by 12 | Viewed by 3430

Abstract

Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the [...] Read more.

Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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Review

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15 pages, 1583 KiB

Open AccessEditor’s ChoiceReview

Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells

by Eri Mukai, Shimpei Fujimoto and Nobuya Inagaki

Biomolecules 2022, 12(9), 1228; https://doi.org/10.3390/biom12091228 - 02 Sep 2022

Cited by 17 | Viewed by 4180

Abstract

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is [...] Read more.

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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15 pages, 1156 KiB

Open AccessReview

Overcoming the Limitations of Stem Cell-Derived Beta Cells

by Mariana V. Karimova, Inessa G. Gvazava and Ekaterina A. Vorotelyak

Biomolecules 2022, 12(6), 810; https://doi.org/10.3390/biom12060810 - 09 Jun 2022

Cited by 6 | Viewed by 3408

Abstract

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to [...] Read more.

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion—one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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16 pages, 721 KiB

Open AccessReview

The Impact of Pancreatic Exocrine Diseases on the β-Cell and Glucose Metabolism—A Review with Currently Available Evidence

by Marina Ciochina, Daniel Vasile Balaban, George Manucu, Mariana Jinga and Cristian Gheorghe

Biomolecules 2022, 12(5), 618; https://doi.org/10.3390/biom12050618 - 21 Apr 2022

Cited by 11 | Viewed by 2801

Abstract

Pancreatic exocrine and endocrine dysfunctions often come together in the course of pancreatic diseases as interdependent manifestations of the same organ. However, the mechanisms underlying the bidirectional connection of the exocrine and endocrine pancreas are not fully understood. In this review, we aimed [...] Read more.

Pancreatic exocrine and endocrine dysfunctions often come together in the course of pancreatic diseases as interdependent manifestations of the same organ. However, the mechanisms underlying the bidirectional connection of the exocrine and endocrine pancreas are not fully understood. In this review, we aimed to synthetize the current knowledge regarding the effects of several exocrine pancreatic pathologies on the homeostasis of β-cells, with a special interest in the predisposition toward diabetes mellitus (DM). We focused on the following pancreatic exocrine diseases: chronic pancreatitis, acute pancreatitis, cystic fibrosis, pancreatic cancer, pancreatic resections, and autoimmune pancreatitis. We discuss the pathophysiologic mechanisms behind the impact on β-cell function and evolution into DM, as well as the associated risk factors in progression to DM, and we describe the most relevant and statistically significant findings in the literature. An early and correct diagnosis of DM in the setting of pancreatic exocrine disorders is of paramount importance for anticipating the disease’s course and its therapeutical needs. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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14 pages, 1258 KiB

Open AccessReview

Roles of mTOR in the Regulation of Pancreatic β-Cell Mass and Insulin Secretion

by Shun-ichiro Asahara, Hiroyuki Inoue, Hitoshi Watanabe and Yoshiaki Kido

Biomolecules 2022, 12(5), 614; https://doi.org/10.3390/biom12050614 - 21 Apr 2022

Cited by 8 | Viewed by 3880

Abstract

Pancreatic β-cells are the only type of cells that can control glycemic levels via insulin secretion. Thus, to explore the mechanisms underlying pancreatic β-cell failure, many reports have clarified the roles of important molecules, such as the mechanistic target of rapamycin (mTOR), which [...] Read more.

Pancreatic β-cells are the only type of cells that can control glycemic levels via insulin secretion. Thus, to explore the mechanisms underlying pancreatic β-cell failure, many reports have clarified the roles of important molecules, such as the mechanistic target of rapamycin (mTOR), which is a central regulator of metabolic and nutrient cues. Studies have uncovered the roles of mTOR in the function of β-cells and the progression of diabetes, and they suggest that mTOR has both positive and negative effects on pancreatic β-cells in the development of diabetes. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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14 pages, 1162 KiB

Open AccessReview

MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms

by Jiani Liang, Margot Chirikjian, Utpal B. Pajvani and Alberto Bartolomé

Biomolecules 2022, 12(4), 535; https://doi.org/10.3390/biom12040535 - 31 Mar 2022

Cited by 6 | Viewed by 3447

Abstract

β-cells are insulin-producing cells in the pancreas that maintain euglycemic conditions. Pancreatic β-cell maturity and function are regulated by a variety of transcription factors that enable the adequate expression of the cellular machinery involved in nutrient sensing and commensurate insulin secretion. One of [...] Read more.

β-cells are insulin-producing cells in the pancreas that maintain euglycemic conditions. Pancreatic β-cell maturity and function are regulated by a variety of transcription factors that enable the adequate expression of the cellular machinery involved in nutrient sensing and commensurate insulin secretion. One of the key factors in this regulation is MAF bZIP transcription factor A (MafA). MafA expression is decreased in type 2 diabetes, contributing to β-cell dysfunction and disease progression. The molecular biology underlying MafA is complex, with numerous transcriptional and post-translational regulatory nodes. Understanding these complexities may uncover potential therapeutic targets to ameliorate β-cell dysfunction. This article will summarize the role of MafA in normal β-cell function and disease, with a special focus on known transcriptional and post-translational regulators of MafA expression Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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18 pages, 1261 KiB

Open AccessReview

Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes

by Hong-Lian Wang, Li Wang, Chang-Ying Zhao and Hui-Yao Lan

Biomolecules 2022, 12(3), 373; https://doi.org/10.3390/biom12030373 - 26 Feb 2022

Cited by 19 | Viewed by 4597

Abstract

Beta (β) cell dysfunction or loss is the common pathological feature in all types of diabetes mellitus (diabetes). Resolving the underlying mechanism may facilitate the treatment of diabetes by preserving the β cell population and function. It is known that TGF-β signaling plays [...] Read more.

Beta (β) cell dysfunction or loss is the common pathological feature in all types of diabetes mellitus (diabetes). Resolving the underlying mechanism may facilitate the treatment of diabetes by preserving the β cell population and function. It is known that TGF-β signaling plays diverse roles in β cell development, function, proliferation, apoptosis, and dedifferentiation. Inhibition of TGF-β signaling expands β cell lineage in the development. However, deletion of Tgfbr1 has no influence on insulin demand-induced but abolishes inflammation-induced β cell proliferation. Among canonical TGF-β signaling, Smad3 but not Smad2 is the predominant repressor of β cell proliferation in response to systemic insulin demand. Deletion of Smad3 simultaneously improves β cell function, apoptosis, and systemic insulin resistance with the consequence of eliminated overt diabetes in diabetic mouse models, revealing Smad3 as a key mediator and ideal therapeutic target for type-2 diabetes. However, Smad7 shows controversial effects on β cell proliferation and glucose homeostasis in animal studies. On the other hand, overexpression of Tgfb1 prevents β cells from autoimmune destruction without influence on β cell function. All these findings reveal the diverse regulatory roles of TGF-β signaling in β cell biology. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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24 pages, 2687 KiB

Open AccessEditor’s ChoiceReview

Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production

by Kristen E. Rohli, Cierra K. Boyer, Sandra E. Blom and Samuel B. Stephens

Biomolecules 2022, 12(2), 335; https://doi.org/10.3390/biom12020335 - 20 Feb 2022

Cited by 16 | Viewed by 4583

Abstract

Pancreatic islet β-cells exhibit tremendous plasticity for secretory adaptations that coordinate insulin production and release with nutritional demands. This essential feature of the β-cell can allow for compensatory changes that increase secretory output to overcome insulin resistance early in Type 2 diabetes (T2D). [...] Read more.

Pancreatic islet β-cells exhibit tremendous plasticity for secretory adaptations that coordinate insulin production and release with nutritional demands. This essential feature of the β-cell can allow for compensatory changes that increase secretory output to overcome insulin resistance early in Type 2 diabetes (T2D). Nutrient-stimulated increases in proinsulin biosynthesis may initiate this β-cell adaptive compensation; however, the molecular regulators of secretory expansion that accommodate the increased biosynthetic burden of packaging and producing additional insulin granules, such as enhanced ER and Golgi functions, remain poorly defined. As these adaptive mechanisms fail and T2D progresses, the β-cell succumbs to metabolic defects resulting in alterations to glucose metabolism and a decline in nutrient-regulated secretory functions, including impaired proinsulin processing and a deficit in mature insulin-containing secretory granules. In this review, we will discuss how the adaptative plasticity of the pancreatic islet β-cell’s secretory program allows insulin production to be carefully matched with nutrient availability and peripheral cues for insulin signaling. Furthermore, we will highlight potential defects in the secretory pathway that limit or delay insulin granule biosynthesis, which may contribute to the decline in β-cell function during the pathogenesis of T2D. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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15 pages, 1521 KiB

Open AccessEditor’s ChoiceReview

Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

by Elisa Fernández-Millán and Carlos Guillén

Biomolecules 2022, 12(1), 104; https://doi.org/10.3390/biom12010104 - 08 Jan 2022

Cited by 12 | Viewed by 4966

Abstract

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells [...] Read more.

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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10 pages, 670 KiB

Open AccessReview

The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes

by Yury Kryvalap and Jan Czyzyk

Biomolecules 2022, 12(1), 67; https://doi.org/10.3390/biom12010067 - 02 Jan 2022

Cited by 12 | Viewed by 2377

Abstract

Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue regeneration and inhibit inflammation may offer a new strategy in therapy development for diabetes and other diseases. Specifically, [...] Read more.

Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue regeneration and inhibit inflammation may offer a new strategy in therapy development for diabetes and other diseases. Specifically, recent efforts have focused on serine protease inhibitors, known as serpins, as potential therapeutic targets. The serpin protein family comprises a broad range of protease inhibitors, which are categorized into 16 clades that are all extracellular, with the exception of Clade B, which controls mostly intracellular proteases, including both serine- and papain-like cysteine proteases. This review discusses the most salient, and sometimes opposing, views that either inhibition or augmentation of protease activity can bring about positive outcomes in pancreatic islet biology and inflammation. These potential discrepancies can be reconciled at the molecular level as specific proteases and serpins regulate distinct signaling pathways, thereby playing equally distinct roles in health and disease development. Full article

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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