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Improvement of pig islet function by in vivo pancreatic tissue remodeling: a "human-like" pig islet structure with streptozotocin treatment.

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Veriter, Sophie [UCL] Aouassar, Najima [UCL] Beaurin, Gwen [UCL] Goebbels, Rose-Marie [UCL] Gianello, Pierre [UCL] Dufrane, Denis [UCL]

Pig islets demonstrate significantly lower insulin secretion after glucose stimulation than human islets (stimulation index of ∼12 vs. 2 for glucose 1 and 15 mM, respectively) due to a major difference in β- and α-cell composition in islets (60% and 25% in humans and 90% and 8% in pigs, respectively). This leads to a lower rise in 3',5'-cyclic adenosine monophosphate (cAMP) in pig β-cells. Since glucagon is the major hormonal effector of cAMP in β-cells, we modified pig islet structure in vivo to increase the proportion of α-cells per islet and to improve insulin secretion. Selected doses (0, 30, 50, 75, and 100 mg/kg) of streptozotocin (STZ) were intravenously injected in 32 young pigs to assess pancreatic (insulin and glucagon) hormone levels, islet remodeling (histomorphometry for α- and β-cell proportions), and insulin and glucagon secretion in isolated islets. Endocrine structure and hormonal content of pig islets were compared with those of human islets. The dose of STZ was significantly correlated with reductions in pancreatic insulin content (p< 0.05, r(2) = 0.77) and the proportion of β-cells (p < 0.05, r(2) = 0.88). A maximum of 50 mg/kg STZ was required for optimal structure remodeling, with an increased proportion of α-cells per islet (26% vs. 48% α-cells per islet for STZ <50 mg/kg vs. >75 mg/kg; p < 0.05) without β-cell dysfunction. Three months after STZ treatment (30/50 mg/kg STZ), pig islets were isolated and compared with isolated control islets (0 mg/kg STZ). Isolated islets from STZ-treated (30/50 mg/kg) pigs had a higher proportion of α-cells than those from control animals (32.0% vs. 9.6%, respectively, p < 0.05). After in vitro stimulation, isolated islets from STZ-treated pigs demonstrated significantly higher glucagon content (65.4 vs. 21.0 ng/ml, p < 0.05) and insulin release (144 µU/ml) than nontreated islets (59 µU/ml, p < 0.05), respectively. Low-dose STZ (<50 mg/kg) can modify the structure of pig islets in vivo and improve insulin secretion after isolation.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Cell Transplantation" - Vol. 22, no.11, p. 2161-2173 (2013)
Peer reviewed yes
Publisher Cognizant Communication Corporation ((United States) Putnam Valley)
issn 0963-6897
e-issn 1555-3892
Publication status Publié
Affiliations UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation
UCL - (SLuc) Centre de thérapie tissulaire et cellulaire
UCL - (SLuc) Service de chirurgie et transplantation abdominale
Keywords Pig islet xenotransplantation ; Islet structure ; Pancreatic tissue remodeling ; Alpha-Cell ; Bêta-Cell stimulation
Links
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Bibliographic reference Veriter, Sophie ; Aouassar, Najima ; Beaurin, Gwen ; Goebbels, Rose-Marie ; Gianello, Pierre ; et. al. Improvement of pig islet function by in vivo pancreatic tissue remodeling: a "human-like" pig islet structure with streptozotocin treatment.. In: Cell Transplantation, Vol. 22, no.11, p. 2161-2173 (2013)
Permanent URL http://hdl.handle.net/2078.1/134926