Ontogeny of Regeneration of β-Cells in the Neonatal Rat after Treatment with Streptozotocin

Thyssen, Sandra M.; Arany, Edith; Hill, David J.

doi:10.1210/en.2005-0396

Cited by 107 publications

(105 citation statements)

References 51 publications

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“…GLP-1-like immunoreactivity was detected by a polyclonal and a monoclonal anti-GLP-1 antibody reacting, respectively, with the mid to C terminal region of GLP-1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and the amidated C-terminus of the peptide (see the Methods). These antibodies generated similar staining patterns with NCI-H716 cells and human islets (ESM Figs 2 and 3).…”

Section: Resultsmentioning

confidence: 99%

“…The corresponding spectra of the GLP-1(7-37) and GLP-1 (7-36) tryptic sequences were matched with the putative digested sequences of the peptides using the sequence editor implemented on BIOTOOLS. GLP-1(7-37) and GLP-1(7-36) peptides were identified by the species at m/z 1105 (aa [21][22][23][24][25][26][27][28] and at m/z 2098 (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Section: Resultsmentioning

confidence: 99%

“…Primary antibodies were: guinea pig polyclonal anti-swine insulin (A0564; DAKO, Carpinteria, CA, USA); mouse monoclonal anti-human/ mouse glucagon (MAB1249, clone 181402; R&D Systems, Abingdon, UK); rat monoclonal anti-somatostatin (ab30788; Abcam, Cambridge, UK); rabbit polyclonal anti-GLP-1 (ab22625; Abcam), which reacts with the mid to C terminal region of GLP-1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], enabling immunoreactivity with N terminal truncated and C terminally extended forms of GLP-1; mouse monoclonal anti-GLP-1 (HYB 147-06; BioPorto Diagnostic, Gentofte, Denmark), which is specific for the amidated C-terminus of the peptide [20]; and rabbit polyclonal antibody to PC1/3 and PC2 (Chemicon, Rosemont, IL, USA). Secondary antibodies were: Alexa Fluor 488: goat anti-guinea pig IgG, goat anti-rabbit IgG, and goat anti-mouse IgG; and Alexa Fluor 594: goat anti-mouse IgG and goat antirabbit IgG (all from Invitrogen, Molecular Probes, Leiden, the Netherlands).…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, GLP-1 amide was found in the pancreas of fetal and neonatal rats [13], and fully processed GLP-1 was produced by insulinoma cell lines and primary rat alpha cells [14]. Furthermore, when partial beta cell loss was induced in neonatal rats by streptozotocin, islet cell regeneration was accompanied by alpha cell hyperplasia, with an altered phenotype of increased GLP-1 synthesis [15]. More recently, a study mainly focused on the alpha cell line, αTC1-6, showed the processing of proglucagon to GLP-1, with the incretin also found in rat and human islets [16], while investigators working on the Psammomys obesus gerbil incidentally observed that human islets could release GLP-1 [17].…”

Section: Introductionmentioning

confidence: 99%

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A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

et al. 2012

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Aims/hypothesis Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients. MethodsThe presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients. Diabetologia (2012) 55:3262-3272 DOI 10.1007/s00125-012-2716 Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2716-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Results Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from nondiabetic isolated islets. Conclusions/interpretation We have shown the presence of a functionally competent GLP-1 system in human pancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

et al. 2012

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“…A role for GLP-1 in neonatal regenerative responses to insult has been established using streptozotocin (STZ, 70 mg/kg) treatment of 4 day old rats that were then monitored for a total of 40 days (Thyssen et al, 2006). This is a well-characterized model showing a 60 % reduction in the number of insulin-immunoreactive cells.…”

Section: Effects Of Glp-1r Activation During Pancreatic Development Amentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Glucagon‐Like Peptide‐1: Actions and Influence on Pancreatic Hormone Function

Davis

Sandoval

2020

Comprehensive Physiology

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GLP-1 was described as an incretin over 30 years ago. GLP-1 is encoded by the preproglucagon gene (Gcg), which is expressed in the intestine, the pancreas, and the central nervous system. GLP-1 activates GLP-1 receptors (GLP-1r) on the β-cell to induce insulin secretion in a glucosedependent manner. GLP-1 also inhibits α-cell secretion of glucagon. As few, if any, GLP-1r are expressed on α-cells, indirect regulation, via β-or δ-cell products has been thought to be the primary mechanism by which GLP-1 inhibits glucagon secretion. However, recent work suggests that there is sufficient expression of GLP-1r on α-cells for direct regulation as well. Although the predominant source of circulating GLP-1 is the intestine, the α-cell becomes a source of GLP-1 when the islet is metabolically stressed. Recent work suggests the possibility that this source of GLP-1 is also be important in regulating nutrient-induced insulin secretion in a paracrine fashion. More work is also accumulating regarding the role of glucagon, another Gcg-derived protein produced by the α-cell, in stimulating insulin secretion by acting on GLP-1r. Altogether, these data clearly demonstrate the important role of Gcg-derived peptides in regulating insulin secretion. Because of GLP-1's important role in glucose homeostasis, it has been implicated in the success of bariatric surgery and has been successfully targeted for the treatment of type 2 diabetes mellitus.

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Ontogeny of Regeneration of β-Cells in the Neonatal Rat after Treatment with Streptozotocin

Cited by 107 publications

References 51 publications

A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Glucagon‐Like Peptide‐1: Actions and Influence on Pancreatic Hormone Function

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