Influence of Donor Age on Mouse Islet Characteristics and Transplantation

Juang, Jyuhn‐Huarng; Hsu, Brend Ray‐Sea; Kuo, Chun‐Yan; Yao, Nan-Kuang

doi:10.3727/000000001783986738

Cited by 16 publications

(4 citation statements)

References 24 publications

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“…Similar proportions (averages of ~85 vs. ~60%) were also found in another study that also indicated declining β-cell proportions in larger human islets (40). Furthermore, while islet insulin content does not seem to be particularly informative regarding GSIS performance neither in human (9) nor in murine islets (41), mouse islets contain more insulin per islet than human ones (18, 38, 42). We did not perform detailed evaluations on these samples, but our results from a smaller set of samples indicate insulin contents of 51.0 ± 9.3 and 10.4 ± 4.1 ng/IEQ for C57BL6 mouse and human islets, respectively.…”

Section: Discussionmentioning

confidence: 99%

Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets

Garnica¹,

Buchwald²

2019

Front. Endocrinol.

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The detailed characterization and quantification of the kinetics of glucose-stimulated insulin secretion (GSIS) by normal pancreatic islets is of considerable interest for characterizing β-cell dysfunction, assessing the quality of isolated islets, and improving the design of artificial pancreas devices. Here, we performed dynamic evaluation of GSIS by human and mouse islets at high temporal resolution (every minute) in response to different glucose steps using an automated multichannel perifusion instrument. In both species, insulin responses were biphasic (a transient first-phase peak followed by a sustained second-phase), and the amount of insulin released showed a sigmoid-type dependence on glucose concentration. However, compared to murine islets, human islets have (1) a less pronounced first-phase response, (2) a flat secretion rate during second-phase response, (3) a left-shifted concentration response (reaching half-maximal response at 7.9 ± 0.4 vs. 13.7 ± 0.6 mM), and (4) an ~3-fold lower maximal secretion rate (8.3 ± 2.3 vs. 23.9 ± 5.1 pg/min/islet at 30 mM glucose). These results can be used to establish a more informative protocol for the calculation of the stimulation index, which is widely used for islet assessment in both research and clinical applications, but without an accepted standard or clear evidence as to what low- to high-glucose steps can provide better characterization of islet function. Data obtained here suggest that human islet functionality might be best characterized with a dynamic stimulation index obtained with a glucose step from a low of 4–5 to a high of 14–17 mM (e.g., G4 → G16).

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Section: Discussionmentioning

confidence: 99%

Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets

Garnica¹,

Buchwald²

2019

Front. Endocrinol.

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“…In human clinical islet transplantation, transplanted islets are counted as islet equivalents but in rodent islet transplantation, transplanted islets are counted as islet absolute numbers. Mouse islets from old donors tend to be larger and higher in insulin content than islets from young donors [24]. Therefore, more β cells and insulin in islet grafts from old donors may contribute to better metabolic control in the recipient mice.…”

Section: Discussionmentioning

confidence: 99%

Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts

Tian¹,

Gao²,

Weng³

et al. 2011

Transplant International

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Summary Exendin‐4 can stimulate β‐cell replication in mice. Whether it can stimulate β‐cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin‐4 on β‐cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine (BrdU) with or without exendin‐4. At 4 weeks post‐transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin+/BrdU+ cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin‐4 treated mice. Mouse islet grafts in exendin‐4 treated mice had significantly more insulin+/BrdU+β cells than in untreated mice (P < 0.01). Human islet grafts from ≤22‐year‐old donors had more insulin+/BrdU+β cells in exendin‐4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from ≥35‐year‐old donors contained few insulin+/BrdU+β cells in exendin‐4 treated or untreated mice. Our data demonstrated that the capacity for β‐cell replication in mouse and human islet grafts is different with and without exendin‐4 treatment and indicated that GLP‐1 agonists can stimulate β‐cell replication in human islets from young donors.

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“…After overnight incubation with and without CSPIO, 30 islets were cultured for 120 min in RPMI medium supplemented with 2.8 mmol/L glucose followed by 16.7 mmol/L glucose. Stimulation indices were calculated by dividing the amount of insulin released with 16.7 mmol/L glucose by that released with 2.8 mmol/L glucose [28]. For perifusion study, 150 islets were placed into a perifusion chamber composed of a barrel of 1 ml plastic tuberculin syringe (TERUBO, Tokyo, Japan) and 2 layers of nylon net with 10 µm pores (Pharmacia, Uppsala, Sweden) placed in the bottom.…”

Section: Methodsmentioning

confidence: 99%

“…Islets were first perifused for 2 h with medium containing 5.6 mmol/L glucose to equilibrate the cellular conditions, and then with medium containing 16.7 mmol/L glucose for 30 min. The perifusate was collected at 1-min intervals throughout the experiment, and all the samples were measured by radioimmunoassay [28].…”

Section: Methodsmentioning

confidence: 99%

Magnetic Resonance Imaging of Mouse Islet Grafts Labeled with Novel Chitosan-Coated Superparamagnetic Iron Oxide Nanoparticles

et al. 2013

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ObjectTo better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles.Materials and MethodsAfter being incubated with and without CSPIO (10 µg/ml), C57BL/6 mouse islets were examined under transmission electron microscope (TEM) and their insulin secretion was measured. Cytotoxicity was examined in α (αTC1) and β (NIT-1 and βTC) cell lines as well as islets. C57BL/6 mice were used as donors and inbred C57BL/6 and Balb/c mice were used as recipients of islet transplantation. Three hundred islets were transplanted under the left kidney capsule of each mouse and then MR was performed in the recipients periodically. At the end of study, the islet graft was removed for histology and TEM studies.ResultsAfter incubation of mouse islets with CSPIO (10 µg/mL), TEM showed CSPIO in endocytotic vesicles of α- and β-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of αTC1, NIT-1 and βTC cell lines as well as islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure.ConclusionOur results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.

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Influence of Donor Age on Mouse Islet Characteristics and Transplantation

Cited by 16 publications

References 24 publications

Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets

Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets

Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts

Magnetic Resonance Imaging of Mouse Islet Grafts Labeled with Novel Chitosan-Coated Superparamagnetic Iron Oxide Nanoparticles

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