Islet Biology and Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 40115

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Special Issue Editors

Senior Research Fellow, School of Medical Sciences, Faculty of Medicine and Health, Head - Islet Biology and Metabolism Laboratory, University of Sydney, Sydney 2006, Australia
Interests: type-2-diabetes associated genes; Beta-cell function; insulin secretory granules
Charles Perkins Centre, The University of Sydney, Sydney, Australia
Interests: islets; insulin; beta-cells; diaebtes; metabolism

Special Issue Information

Dear Colleagues,

The pancreatic islet and its function represents a core component of metabolic health, particularly in the context of metabolic diseases such as Type 1 and 2 diabetes.

This Special Issue of Metabolites, entitled “Islet Biology and Metabolism,” is dedicated to islet research and the impact of islet function in metabolic health and disease. Specific topics include, but are not limited to, islet hormone processing and secretion, islet transplant research, novel proteins of the insulin secretory pathway, as well as islet drug targets for the management of T1D and T2D. We also invite manuscripts that utilise novel techniques and methodologies in islet biology research, noting the technological advancements in single cell analysis, proteomics, and metabolomics in recent years that have allowed for more in-depth analyses of islet physiology.

Dr. Melkam Kebede
Dr. Belinda Yau
Guest Editors

Manuscript Submission Information

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Keywords

  • Islets
  • Insulin
  • Exocytosis
  • Granules

Published Papers (13 papers)

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Editorial

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3 pages, 169 KiB  
Editorial
Islet Biology and Metabolism
by Belinda Yau and Melkam A. Kebede
Metabolites 2021, 11(11), 786; https://doi.org/10.3390/metabo11110786 - 18 Nov 2021
Viewed by 1500
Abstract
This Special Issue, Islet Biology and Metabolism, was intended as a collection of studies highlighting the importance of the pancreatic islet—in both form and function—to our growing understanding of metabolic physiology and disease [...] Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)

Research

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8 pages, 612 KiB  
Article
Knockout of the Amino Acid Transporter SLC6A19 and Autoimmune Diabetes Incidence in Female Non-Obese Diabetic (NOD) Mice
by Matthew F. Waters, Viviane Delghingaro-Augusto, Kiran Javed, Jane E. Dahlstrom, Gaetan Burgio, Stefan Bröer and Christopher J. Nolan
Metabolites 2021, 11(10), 665; https://doi.org/10.3390/metabo11100665 - 29 Sep 2021
Cited by 2 | Viewed by 2081
Abstract
High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter [...] Read more.
High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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21 pages, 5054 KiB  
Article
Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model
by Danielle J. Borg, Pouya Faridi, Kai Lin Giam, Peta Reeves, Amelia K. Fotheringham, Domenica A. McCarthy, Sherman Leung, Micheal S. Ward, Brooke E. Harcourt, Rochelle Ayala, Jean L. Scheijen, David Briskey, Nadine L. Dudek, Casper G. Schalkwijk, Raymond Steptoe, Anthony W. Purcell and Josephine M. Forbes
Metabolites 2021, 11(7), 426; https://doi.org/10.3390/metabo11070426 - 28 Jun 2021
Cited by 2 | Viewed by 2932
Abstract
Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in [...] Read more.
Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50–100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate β-cell effects, NOD-derived MIN6N8 β-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10–12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts β-cell function. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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7 pages, 792 KiB  
Article
Respiratory Parameters for the Classification of Dysfunctional Insulin Secretion by Pancreatic Islets
by Uma D. Kabra, Charles Affourtit and Martin Jastroch
Metabolites 2021, 11(6), 405; https://doi.org/10.3390/metabo11060405 - 21 Jun 2021
Cited by 4 | Viewed by 2336
Abstract
The development of obesity and type 2 diabetes (T2D) has been associated with impaired mitochondrial function. In pancreatic beta (β) cells, mitochondrial energy metabolism plays a central role in triggering and controlling glucose-stimulated insulin secretion (GSIS). Here, we have explored whether mitochondrial bioenergetic [...] Read more.
The development of obesity and type 2 diabetes (T2D) has been associated with impaired mitochondrial function. In pancreatic beta (β) cells, mitochondrial energy metabolism plays a central role in triggering and controlling glucose-stimulated insulin secretion (GSIS). Here, we have explored whether mitochondrial bioenergetic parameters assessed with Seahorse extracellular flux technology can quantitatively predict insulin secretion. We metabolically stressed male C57BL/6 mice by high-fat feeding (HFD) and measured the glucose sensitivity of islet respiration and insulin secretion. The diet-induced obese (DIO) mice developed hyperinsulinemia, but no pathological secretory differences were apparent between isolated DIO and chow islets. Real-time extracellular flux analysis, however, revealed a lower respiratory sensitivity to glucose in DIO islets. Correlation of insulin secretion with respiratory parameters uncovers compromised insulin secretion in DIO islets by oxidative power. Normalization to increased insulin contents during DIO improves the quantitative relation between GSIS and respiration, allowing to classify dysfunctional properties of pancreatic insulin secretion, and thereby serving as valuable biomarker for pancreatic islet glucose responsiveness and health. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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14 pages, 2876 KiB  
Article
The Capacity to Secrete Insulin Is Dose-Dependent to Extremely High Glucose Concentrations: A Key Role for Adenylyl Cyclase
by Katherine M. Gerber, Nicholas B. Whitticar, Daniel R. Rochester, Kathryn L. Corbin, William J. Koch and Craig S. Nunemaker
Metabolites 2021, 11(6), 401; https://doi.org/10.3390/metabo11060401 - 19 Jun 2021
Cited by 4 | Viewed by 3195
Abstract
Insulin secretion is widely thought to be maximally stimulated in glucose concentrations of 16.7-to-30 mM (300-to-540 mg/dL). However, insulin secretion is seldom tested in hyperglycemia exceeding these levels despite the Guinness World Record being 147.6 mM (2656 mg/dL). We investigated how islets respond [...] Read more.
Insulin secretion is widely thought to be maximally stimulated in glucose concentrations of 16.7-to-30 mM (300-to-540 mg/dL). However, insulin secretion is seldom tested in hyperglycemia exceeding these levels despite the Guinness World Record being 147.6 mM (2656 mg/dL). We investigated how islets respond to 1-h exposure to glucose approaching this record. Insulin secretion from human islets at 12 mM glucose intervals dose-dependently increased until at least 72 mM glucose. Murine islets in 84 mM glucose secreted nearly double the insulin as in 24 mM (p < 0.001). Intracellular calcium was maximally stimulated in 24 mM glucose despite a further doubling of insulin secretion in higher glucose, implying that insulin secretion above 24 mM occurs through amplifying pathway(s). Increased osmolarity of 425-mOsm had no effect on insulin secretion (1-h exposure) or viability (48-h exposure) in murine islets. Murine islets in 24 mM glucose treated with a glucokinase activator secreted as much insulin as islets in 84 mM glucose, indicating that glycolytic capacity exists above 24 mM. Using an incretin mimetic and an adenylyl cyclase activator in 24 mM glucose enhanced insulin secretion above that observed in 84 mM glucose while adenylyl cyclase inhibitor reduced stimulatory effects. These results highlight the underestimated ability of islets to secrete insulin proportionally to extreme hyperglycemia through adenylyl cyclase activity. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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15 pages, 9840 KiB  
Article
Ectopic Leptin Production by Intraocular Pancreatic Islet Organoids Ameliorates the Metabolic Phenotype of ob/ob Mice
by Barbara Leibiger, Tilo Moede, Ismael Valladolid-Acebes, Meike Paschen, Montse Visa, Ingo B. Leibiger and Per-Olof Berggren
Metabolites 2021, 11(6), 387; https://doi.org/10.3390/metabo11060387 - 14 Jun 2021
Cited by 3 | Viewed by 2648
Abstract
The pancreatic islets of Langerhans consist of endocrine cells that secrete peptide hormones into the blood circulation in response to metabolic stimuli. When transplanted into the anterior chamber of the eye (ACE), pancreatic islets engraft and maintain morphological features of native islets as [...] Read more.
The pancreatic islets of Langerhans consist of endocrine cells that secrete peptide hormones into the blood circulation in response to metabolic stimuli. When transplanted into the anterior chamber of the eye (ACE), pancreatic islets engraft and maintain morphological features of native islets as well as islet-specific vascularization and innervation patterns. In sufficient amounts, intraocular islets are able to maintain glucose homeostasis in diabetic mice. Islet organoids (pseudo-islets), which are formed by self-reassembly of islet cells following disaggregation and genetic manipulation, behave similarly to native islets. Here, we tested the hypothesis that genetically engineered intraocular islet organoids can serve as production sites for leptin. To test this hypothesis, we chose the leptin-deficient ob/ob mouse as a model system, which becomes severely obese, hyperinsulinemic, hyperglycemic, and insulin resistant. We generated a Tet-OFF-based beta-cell-specific adenoviral expression construct for mouse leptin, which allowed efficient transduction of native beta-cells, optical monitoring of leptin expression by co-expressed fluorescent proteins, and the possibility to switch-off leptin expression by treatment with doxycycline. Intraocular transplantation of islet organoids formed from transduced islet cells, which lack functional leptin receptors, to ob/ob mice allowed optical monitoring of leptin expression and ameliorated their metabolic phenotype by improving bodyweight, glucose tolerance, serum insulin, and C-peptide levels. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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14 pages, 57928 KiB  
Article
Machine Learning Algorithms, Applied to Intact Islets of Langerhans, Demonstrate Significantly Enhanced Insulin Staining at the Capillary Interface of Human Pancreatic β Cells
by Louise Cottle, Ian Gilroy, Kylie Deng, Thomas Loudovaris, Helen E. Thomas, Anthony J. Gill, Jaswinder S. Samra, Melkam A. Kebede, Jinman Kim and Peter Thorn
Metabolites 2021, 11(6), 363; https://doi.org/10.3390/metabo11060363 - 07 Jun 2021
Cited by 2 | Viewed by 2809
Abstract
Pancreatic β cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. β cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the [...] Read more.
Pancreatic β cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. β cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the intimate spatial connections between β cells and these capillaries, which lead to the targeting of insulin secretion to the region where the β cells contact the capillary basement membrane. In addition, β cells orientate with respect to the capillary contact point and many proteins are differentially distributed at the capillary interface compared with the rest of the cell. Here, we set out to develop an automated image analysis approach to identify individual β cells within intact islets and to determine if the distribution of insulin across the cells was polarised. Our results show that a U-Net machine learning algorithm correctly identified β cells and their orientation with respect to the capillaries. Using this information, we then quantified insulin distribution across the β cells to show enrichment at the capillary interface. We conclude that machine learning is a useful analytical tool to interrogate large image datasets and analyse sub-cellular organisation. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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13 pages, 1183 KiB  
Article
Successful Islet Outcomes Using Australia-Wide Donors: A National Centre Experience
by Wayne J Hawthorne, Sussan Davies, Hee-chang Mun, Yi Vee Chew, Lindy Williams, Patricia Anderson, Natasha Rogers and Philip J O’Connell
Metabolites 2021, 11(6), 360; https://doi.org/10.3390/metabo11060360 - 05 Jun 2021
Cited by 2 | Viewed by 2191
Abstract
Cold ischemia and hence travel time can adversely affect outcomes of islet isolation. The aim of this study was to compare the isolation and transplant outcomes of donor pancreata according to the distance from islet isolation facility. Principally, those within a 50 km [...] Read more.
Cold ischemia and hence travel time can adversely affect outcomes of islet isolation. The aim of this study was to compare the isolation and transplant outcomes of donor pancreata according to the distance from islet isolation facility. Principally, those within a 50 km radius of the centre were compared with those from regional areas within the state and those from interstate donors within Australia. Organ donors were categorised according to distance from National Pancreas Transplant Unit Westmead (NPTU). Donor characteristics were analysed statistically against islet isolation outcomes. These were age, BMI, cause and mechanism of death, days in ICU, gender, inotrope and steroid use, cold ischemia time (CIT) and retrieval surgical team. Between March 2007 and December 2020, 297 islet isolations were performed at our centre. A total of 149 donor pancreata were local area, and 148 non-local regions. Mean distance from the isolation facility was 780.05 km. Mean pancreas CIT was 401.07 ± 137.71 min and was significantly different between local and non-local groups (297.2 vs. 487.5 min, p < 0.01). Mean age of donors was 45.22 years, mean BMI was 28.82, sex ratio was 48:52 F:M and mean time in ICU was 3.07 days. There was no significant difference between local and non-local for these characteristics. The mean CIT resulting in islet transplantation was 297.1 ± 91.5 min and longest CIT resulting in transplantation was 676 min. There was no significant difference in islet isolation outcomes between local and non-local donors for characteristics other than CIT. There was also no significant effect of distance from the isolation facility on positive islet transplant outcomes (C-peptide > 0.2 at 1 month post-transplant). Conclusions: Distance from the isolation centre did not impact on isolation or transplant outcomes supporting the ongoing nationwide use of shipping pancreata for islet isolation and transplantation. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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Review

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32 pages, 30880 KiB  
Review
Inside the Insulin Secretory Granule
by Mark Germanos, Andy Gao, Matthew Taper, Belinda Yau and Melkam A. Kebede
Metabolites 2021, 11(8), 515; https://doi.org/10.3390/metabo11080515 - 05 Aug 2021
Cited by 18 | Viewed by 5020
Abstract
The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with [...] Read more.
The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the trans-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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18 pages, 1352 KiB  
Review
Understanding the Long-Lasting Effects of Fetal Nutrient Restriction versus Exposure to an Obesogenic Diet on Islet-Cell Mass and Function
by Stephanie E. O’Hara, Kelly M. Gembus and Lisa M. Nicholas
Metabolites 2021, 11(8), 514; https://doi.org/10.3390/metabo11080514 - 04 Aug 2021
Cited by 4 | Viewed by 2395
Abstract
Early life represents a window of phenotypic plasticity. Thus, exposure of the developing fetus to a compromised nutritional environment can have long term consequences for their health. Indeed, undernutrition or maternal intake of an obesogenic diet during pregnancy leads to a heightened risk [...] Read more.
Early life represents a window of phenotypic plasticity. Thus, exposure of the developing fetus to a compromised nutritional environment can have long term consequences for their health. Indeed, undernutrition or maternal intake of an obesogenic diet during pregnancy leads to a heightened risk of type 2 diabetes (T2D) and obesity in her offspring in adult life. Given that abnormalities in beta-cell function are crucial in delineating the risk of T2D, studies have investigated the impact of these exposures on islet morphology and beta-cell function in the offspring in a bid to understand why they are more at risk of T2D. Interestingly, despite the contrasting maternal metabolic phenotype and, therefore, intrauterine environment associated with undernutrition versus high-fat feeding, there are a number of similarities in the genes/biological pathways that are disrupted in offspring islets leading to changes in function. Looking to the future, it will be important to define the exact mechanisms involved in mediating changes in the gene expression landscape in islet cells to determine whether the road to T2D development is the same or different in those exposed to different ends of the nutritional spectrum. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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16 pages, 14101 KiB  
Review
What Is the Metabolic Amplification of Insulin Secretion and Is It (Still) Relevant?
by Ingo Rustenbeck, Torben Schulze, Mai Morsi, Mohammed Alshafei and Uwe Panten
Metabolites 2021, 11(6), 355; https://doi.org/10.3390/metabo11060355 - 02 Jun 2021
Cited by 14 | Viewed by 3224
Abstract
The pancreatic beta-cell transduces the availability of nutrients into the secretion of insulin. While this process is extensively modified by hormones and neurotransmitters, it is the availability of nutrients, above all glucose, which sets the process of insulin synthesis and secretion in motion. [...] Read more.
The pancreatic beta-cell transduces the availability of nutrients into the secretion of insulin. While this process is extensively modified by hormones and neurotransmitters, it is the availability of nutrients, above all glucose, which sets the process of insulin synthesis and secretion in motion. The central role of the mitochondria in this process was identified decades ago, but how changes in mitochondrial activity are coupled to the exocytosis of insulin granules is still incompletely understood. The identification of ATP-sensitive K+-channels provided the link between the level of adenine nucleotides and the electrical activity of the beta cell, but the depolarization-induced Ca2+-influx into the beta cells, although necessary for stimulated secretion, is not sufficient to generate the secretion pattern as produced by glucose and other nutrient secretagogues. The metabolic amplification of insulin secretion is thus the sequence of events that enables the secretory response to a nutrient secretagogue to exceed the secretory response to a purely depolarizing stimulus and is thus of prime importance. Since the cataplerotic export of mitochondrial metabolites is involved in this signaling, an orienting overview on the topic of nutrient secretagogues beyond glucose is included. Their judicious use may help to define better the nature of the signals and their mechanism of action. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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15 pages, 671 KiB  
Review
FFAR from the Gut Microbiome Crowd: SCFA Receptors in T1D Pathology
by Medha Priyadarshini, Kristen Lednovich, Kai Xu, Sophie Gough, Barton Wicksteed and Brian T. Layden
Metabolites 2021, 11(5), 302; https://doi.org/10.3390/metabo11050302 - 11 May 2021
Cited by 10 | Viewed by 3682
Abstract
The gut microbiome has emerged as a novel determinant of type 1 diabetes (T1D), but the underlying mechanisms are unknown. In this context, major gut microbial metabolites, short-chain fatty acids (SCFAs), are considered to be an important link between the host and gut [...] Read more.
The gut microbiome has emerged as a novel determinant of type 1 diabetes (T1D), but the underlying mechanisms are unknown. In this context, major gut microbial metabolites, short-chain fatty acids (SCFAs), are considered to be an important link between the host and gut microbiome. We, along with other laboratories, have explored how SCFAs and their cognate receptors affect various metabolic conditions, including obesity, type 2 diabetes, and metabolic syndrome. Though gut microbiome and SCFA-level changes have been reported in T1D and in mouse models of the disease, the role of SCFA receptors in T1D remains under explored. In this review article, we will highlight the existing and possible roles of these receptors in T1D pathology. We conclude with a discussion of SCFA receptors as therapeutic targets for T1D, exploring an exciting new potential for novel treatments of glucometabolic disorders. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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16 pages, 2024 KiB  
Review
Isolation and Proteomics of the Insulin Secretory Granule
by Nicholas Norris, Belinda Yau and Melkam Alamerew Kebede
Metabolites 2021, 11(5), 288; https://doi.org/10.3390/metabo11050288 - 30 Apr 2021
Cited by 15 | Viewed by 4424
Abstract
Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), [...] Read more.
Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), defects in insulin action results in peripheral insulin resistance and beta-cell compensation, ultimately leading to dysfunctional ISG production and secretion. ISGs are functionally dynamic and many proteins present either on the membrane or in the lumen of the ISG may modulate and affect different stages of ISG trafficking and secretion. Previously, studies have identified few ISG proteins and more recently, proteomics analyses of purified ISGs have uncovered potential novel ISG proteins. This review summarizes the proteins identified in the current ISG proteomes from rat insulinoma INS-1 and INS-1E cell lines. Here, we also discuss techniques of ISG isolation and purification, its challenges and potential future directions. Full article
(This article belongs to the Special Issue Islet Biology and Metabolism)
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