Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography

Grong, Eivind; Kulseng, Bård; Arbo, Ingerid; Nord, Christoffer; Eriksson, Maria; Ahlgren, Ulf; Mårvik, Ronald

doi:10.1007/s00464-015-4236-4

Cited by 16 publications

(9 citation statements)

References 54 publications

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“…To corroborate the results obtained from our ACE-platform and to assess how STZ induces β-cell destruction in the pancreas on the whole organ level (i.e., including the complete range of islets with maintained topological information), we next turned to optical projection tomography (OPT) imaging 18 , enabling assessments of individual islet β-cell volumes, and their spatial 3D coordinates throughout the volume of intact pancreata [19][20][21][22] . We performed two modes of STZ administration, SHD-STZ and MLD-STZ, to additionally investigate possible differences in the outcome of these procedures on the extent and/or kinetics of β-cell destruction.…”

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confidence: 99%

Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes

et al. 2020

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Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.

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confidence: 99%

Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes

et al. 2020

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“…Previously, we developed an optical projection tomography (OPT) 9 based approach that enables detailed extraction of the islet distribution throughout the volume of the intact pancreas 10 11 . Hereby, individual islet β-cell volumes and their spatial 3D coordinates may be derived in large cohorts of animals 12 13 14 . In this study we used OPT imaging to describe the development of islet hypertrophy in the ob / ob mouse between 4 and 52 weeks of age.…”

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confidence: 99%

Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas

Parween

Kostromina

Nord

et al. 2016

Sci Rep

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The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.

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“…However, there are doubts about this due to a recent study with a modified mouse model involving an inducible knockdown of GLP-1r in beta-cells (GLP1rβ-cell-ko), which showed improved glycemic profiles, to the wild-nature level, after SG [ 21 ]. Other researchers have linked the maintenance of beta-cell mass and beta-cell identity markers such as PDX-1 or MafA [ 22 ] (Picture 2) to high levels of gastrin after SG, as well as to correction of long-term blood glucose levels in rodents [ 23 ].…”

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confidence: 99%

Sleeve Gastrectomy and Roux-En-Y Gastric Bypass. Two Sculptors of the Pancreatic Islet

Pérez-Arana

Fernández-Vivero

Camacho-Ramírez

et al. 2021

JCM

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Several surgical procedures are performed for the treatment of obesity. A main outcome of these procedures is the improvement of type 2 diabetes mellitus. Trying to explain this, gastrointestinal hormone levels and their effect on organs involved in carbohydrate metabolism, such as liver, gut, muscle or fat, have been studied intensively after bariatric surgery. These effects on endocrine-cell populations in the pancreas have been less well studied. We gathered the existing data on these pancreatic-cell populations after the two most common types of bariatric surgery, the sleeve gastrectomy (SG) and the roux-en-Y gastric bypass (RYGB), with the aim to explain the pathophysiological mechanisms underlying these surgeries and to improve their outcome.

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Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography

Cited by 16 publications

References 54 publications

Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes

Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes

Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas

Sleeve Gastrectomy and Roux-En-Y Gastric Bypass. Two Sculptors of the Pancreatic Islet

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