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Editorial

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Open AccessEditorial

Editorial on the Special Issue: “Pancreatic Islets of Langerhans: Not Only Beta-Cells”

by Roberta Malaguarnera and Salvatore Piro

Biomolecules 2021, 11(11), 1646; https://doi.org/10.3390/biom11111646 - 07 Nov 2021

Viewed by 1222

Abstract

This year marks the centenary of the discovery of insulin [...] Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

Research

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12 pages, 10422 KiB

Open AccessFeature PaperArticle

A Systematic Comparison of Protocols for Recovery of High-Quality RNA from Human Islets Extracted by Laser Capture Microdissection

by Chiara M. A. Cefalo, Teresa Mezza, Andrea Giaccari and Rohit N. Kulkarni

Biomolecules 2021, 11(5), 625; https://doi.org/10.3390/biom11050625 - 22 Apr 2021

Cited by 5 | Viewed by 2501

Abstract

The isolation of high-quality RNA from endocrine pancreas sections represents a considerable challenge largely due to the high ribonuclease levels. Laser capture microdissection (LCM) of mammalian islets, in association with RNA extraction protocols, has emerged as a feasible approach to characterizing their genetic [...] Read more.

The isolation of high-quality RNA from endocrine pancreas sections represents a considerable challenge largely due to the high ribonuclease levels. Laser capture microdissection (LCM) of mammalian islets, in association with RNA extraction protocols, has emerged as a feasible approach to characterizing their genetic and proteomic profiles. However, a validated protocol to obtain high-quality RNA from LCM-derived human pancreas specimens that is appropriate for next-generation sequencing analysis is still lacking. In this study, we applied four methods (Picopure extraction kit, Qiazol protocol, Qiazol + Clean-up kit, and RNeasy Microkit + Carrier) to extract RNA from human islets obtained from both non-diabetic individuals and patients with type 2 diabetes who had undergone partial pancreatectomy, as well as handpicked islets from both non-diabetic and diabetic organ donors. The yield and purity of total RNA were determined by 260/280 absorbance using Nanodrop 100 and the RNA integrity number with a bioanalyzer. The results indicated that among the four methods, the RNeasy MicroKit + Carrier (Qiagen) provides the highest yield and purity. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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10 pages, 1610 KiB

Open AccessFeature PaperArticle

Pro-Inflammatory Cytokines Induce Insulin and Glucagon Double Positive Human Islet Cells That Are Resistant to Apoptosis

by Marta Tesi, Marco Bugliani, Gianmarco Ferri, Mara Suleiman, Carmela De Luca, Emanuele Bosi, Matilde Masini, Vincenzo De Tata, Conny Gysemans, Francesco Cardarelli, Miriam Cnop, Decio L. Eizirik, Piero Marchetti and Lorella Marselli

Biomolecules 2021, 11(2), 320; https://doi.org/10.3390/biom11020320 - 19 Feb 2021

Cited by 9 | Viewed by 3384

Abstract

The presence of islet cells double positive for insulin and glucagon (Ins⁺/Glu⁺) has been described in the pancreas from both type 2 (T2D) and type 1 (T1D) diabetic subjects. We studied the role of pro-inflammatory cytokines on the occurrence, [...] Read more.

The presence of islet cells double positive for insulin and glucagon (Ins⁺/Glu⁺) has been described in the pancreas from both type 2 (T2D) and type 1 (T1D) diabetic subjects. We studied the role of pro-inflammatory cytokines on the occurrence, trajectory, and characteristics of Ins⁺/Glu⁺ cells in human pancreatic islets. Pancreas samples, isolated islets, and dispersed islet cells from 3 T1D and 11 non-diabetic (ND) multi-organ donors were studied by immunofluorescence, confocal microscopy, and/or electron microscopy. ND islet cells were exposed to interleukin-1β and interferon-γ for up to 120 h. In T1D islets, we confirmed an increased prevalence of Ins⁺/Glu⁺ cells. Cytokine-exposed islets showed a progressive increase of Ins⁺/Glu⁺ cells that represented around 50% of endocrine cells after 120h. Concomitantly, cells expressing insulin granules only decreased significantly over time, whereas those containing only glucagon granules remained stable. Interestingly, Ins⁺/Glu⁺ cells were less prone to cytokine-induced apoptosis than cells containing only insulin. Cytokine-exposed islets showed down-regulation of β-cell identity genes. In conclusion, pro-inflammatory cytokines induce Ins⁺/Glu⁺ cells in human islets, possibly due to a switch from a β- to a β-/α-cell phenotype. These Ins⁺/Glu⁺ cells appear to be resistant to cytokine-induced apoptosis. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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12 pages, 9456 KiB

Open AccessArticle

Glucagon Prevents Cytotoxicity Induced by Methylglyoxal in a Rat Neuronal Cell Line Model

by Mohammad Sarif Mohiuddin, Tatsuhito Himeno, Yuichiro Yamada, Yoshiaki Morishita, Masaki Kondo, Shin Tsunekawa, Yoshiro Kato, Jiro Nakamura and Hideki Kamiya

Biomolecules 2021, 11(2), 287; https://doi.org/10.3390/biom11020287 - 15 Feb 2021

Cited by 11 | Viewed by 2995

Abstract

Although diabetic polyneuropathy (DPN) is a frequent diabetic complication, no effective therapeutic approach has been established. Glucagon is a crucial hormone for glucose homeostasis but has pleiotropic effects, including neuroprotective effects in the central nervous system. However, the importance of glucagon in the [...] Read more.

Although diabetic polyneuropathy (DPN) is a frequent diabetic complication, no effective therapeutic approach has been established. Glucagon is a crucial hormone for glucose homeostasis but has pleiotropic effects, including neuroprotective effects in the central nervous system. However, the importance of glucagon in the peripheral nervous system (PNS) has not been clarified. Here, we hypothesized that glucagon might have a neuroprotective function in the PNS. The immortalized rat dorsal root ganglion (DRG) neuronal cell line 50B11 was treated with methylglyoxal (MG) to mimic an in vitro DPN model. The cells were cultured with or without glucagon or MG. Neurotoxicity, survival, apoptosis, neurite projection, cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were examined. Glucagon had no cytotoxicity and rescued the cells from neurotoxicity. Cell survival was increased by glucagon. The ratio of apoptotic cells, which was increased by MG, was reduced by glucagon. Neurite outgrowth was accelerated in glucagon-treated cells. Cyclic AMP and PKA accumulated in the cells after glucagon stimulation. In conclusion, glucagon protected the DRG neuronal cells from MG-induced cellular stress. The cAMP/PKA pathway may have significant roles in those protective effects of glucagon. Glucagon may be a potential target for the treatment of DPN. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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15 pages, 2096 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Direct Effects of D-Chiro-Inositol on Insulin Signaling and Glucagon Secretion of Pancreatic Alpha Cells

by Agnese Filippello, Alessandra Scamporrino, Stefania Di Mauro, Roberta Malaguarnera, Antonino Di Pino, Roberto Scicali, Francesco Purrello and Salvatore Piro

Biomolecules 2020, 10(10), 1404; https://doi.org/10.3390/biom10101404 - 04 Oct 2020

Cited by 11 | Viewed by 3328

Abstract

The insulin resistance state of pancreatic α-cells seems to be related to glucagon hypersecretion in type 2 diabetes. Treatment that can improve the insulin sensitivity of α-cells could control glucagon levels in patients with diabetes mellitus. The aim of this study was to [...] Read more.

The insulin resistance state of pancreatic α-cells seems to be related to glucagon hypersecretion in type 2 diabetes. Treatment that can improve the insulin sensitivity of α-cells could control glucagon levels in patients with diabetes mellitus. The aim of this study was to investigate the preventive role of D-chiro-inositol (DCI), which has insulin receptor-sensitizer effects on insulin signaling pathways and glucagon secretion in pancreatic α-TC1 clone 6 cells. Cells were chronically treated with palmitate to induce insulin resistance in the presence/absence of DCI. DCI treatment improved the insulin signaling pathway and restored insulin-mediated glucagon suppression in α-TC1-6 cells exposed to palmitate. These results indicate that DCI treatment prevents the insulin resistance of α-TC1-6 cells chronically exposed to palmitate. Our data provide evidence that DCI could be useful to improve the insulin sensitivity of pancreatic α-cells in diabetes treatment. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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28 pages, 3716 KiB

Open AccessArticle

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse

by Blandine Gausserès, Junjun Liu, Ewout Foppen, Cécile Tourrel-Cuzin, Ana Rodriguez Sanchez-Archidona, Etienne Delangre, Céline Cruciani-Guglielmacci, Stéphanie Pons, Uwe Maskos, Bernard Thorens, Christophe Magnan, Jamileh Movassat and Kamel Maouche

Biomolecules 2020, 10(7), 1057; https://doi.org/10.3390/biom10071057 - 16 Jul 2020

Cited by 7 | Viewed by 2920

Abstract

Objective: Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D [...] Read more.

Objective: Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D remains undefined. We investigated whether the systemic lack of α7 nAChR was sufficient to impair glucose homeostasis. Methods: We used an α7 nAChR knock-out (α7^−/−) mouse model fed a standard chow diet. The effects of the lack of α7 nAChR on islet mass, insulin secretion, glucose and insulin tolerance, body composition, and food behaviour were assessed in vivo and ex vivo experiments. Results: Young α7^−/− mice display a chronic mild high glycemia combined with an impaired glucose tolerance and a marked deficit in β-cell mass. In addition to these metabolic disorders, old mice developed adipose tissue inflammation, elevated plasma free fatty acid concentrations and presented glycolytic muscle insulin resistance in old mice. Finally, α7^−/− mice, fed a chow diet, exhibited a late-onset excessive gain in body weight through increased fat mass associated with higher food intake. Conclusion: Our work highlights the important role of α7 nAChR in glucose homeostasis. The constitutive lack of α7 nAChR suggests a novel pathway influencing the pathogenesis of T2D. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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Review

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19 pages, 1038 KiB

Open AccessReview

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

by Francesca Porcellati, Stefania Di Mauro, Alessio Mazzieri, Alessandra Scamporrino, Agnese Filippello, Michelantonio De Fano, Carmine Giuseppe Fanelli, Francesco Purrello, Roberta Malaguarnera and Salvatore Piro

Biomolecules 2021, 11(9), 1281; https://doi.org/10.3390/biom11091281 - 27 Aug 2021

Cited by 5 | Viewed by 3744

Abstract

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in [...] Read more.

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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23 pages, 2410 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity

by Nicola Marrano, Giuseppina Biondi, Anna Borrelli, Angelo Cignarelli, Sebastio Perrini, Luigi Laviola, Francesco Giorgino and Annalisa Natalicchio

Biomolecules 2021, 11(2), 286; https://doi.org/10.3390/biom11020286 - 15 Feb 2021

Cited by 20 | Viewed by 4954

Abstract

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different [...] Read more.

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Irisin, a myokine released in response to a high-fat diet and exercise, enhances GSIS. Similar to GLP-1, irisin augments insulin biosynthesis and promotes accrual of β-cell functional mass. In addition, irisin and GLP-1 share comparable pleiotropic effects and activate similar intracellular pathways. The insulinotropic and extra-pancreatic effects of GLP-1 are reduced in type 2 diabetes (T2D) patients but preserved at pharmacological doses. GLP-1 receptor agonists (GLP-1RAs) are therefore among the most widely used antidiabetes drugs, also considered for their cardiovascular benefits and ability to promote weight loss. Irisin levels are lower in T2D patients, and in diabetic and/or obese animal models irisin administration improves glycemic control and promotes weight loss. Interestingly, recent evidence suggests that both GLP-1 and irisin are also synthesized within the pancreatic islets, in α- and β-cells, respectively. This review aims to describe the similarities between GLP-1 and irisin and to propose a new potential axis–involving the gut, muscle, and endocrine pancreas that controls energy homeostasis. Full article

(This article belongs to the Special Issue Pancreatic Islets of Langerhans: Not Only Beta-Cells)

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