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Improved insulin secretory function and reduced chemotactic properties after tissue culture of islets from type 1 diabetic patients
Author(s) -
Lupi Roberto,
Marselli Lorella,
Dionisi Sabrina,
Del Guerra Silvia,
Boggi Ugo,
Del Chiaro Marco,
Lencioni Cristina,
Bugliani Marco,
Mosca Franco,
Di Mario Umberto,
Del Prato Stefano,
Dotta Francesco,
Marchetti Piero
Publication year - 2004
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.460
Subject(s) - medicine , endocrinology , glucokinase , insulin , type 1 diabetes , pancreatic islets , glycolysis , pyruvate kinase , diabetes mellitus , cytokine , chemistry , islet , metabolism
Background Type 1 diabetes results from the destruction of pancreatic beta‐cell as a consequence of an autoimmune process. To date, information on the properties of islets isolated from type 1 diabetic patients is very scant. Methods Some immunological and functional properties of islets prepared from the pancreas of type 1 diabetic patients were studied shortly after the isolation and after a period of culture in euglycemic condition. Results Compared to control islets, freshly prepared type 1 diabetic islets released a significantly higher amount of cytokines (pg/mL) into the culture medium (TNF‐α: 112.9 ± 5.6 vs 75.6 ± 24.4; INF‐γ: 286.9 ± 26.9 vs 58.6 ± 6.2; IL‐10: 41.8 ± 4.3 vs 10.1 ± 3.2; TGF‐1 β: 294.0 ± 20.6 vs 45.1 ± 3.5); had a significantly higher chemotactic index (1.9 ± 0.2 vs 1.2 ± 0.1); showed reduced insulin release (% of insulin content) in response to glucose (2.8 ± 0.7 vs 5.3 ± 1.9), arginine (3.0 ± 0.6 vs 5.6 ± 1.0), and glibenclamide (2.9 ± 0.7 vs 5.4 ± 0.9); and exhibited decreased glucose oxidation capability and diminished mRNA expression of glucokinase, aldolase, pyruvate kinase, and mitochondrial glycerolphosphate dehydrogenase. Ten days after isolation, a normalization of cytokine release (TNF‐α: 55.7 ± 2.3; INF‐γ: 53.9 ± 4.3; IL‐10: 8.6 ± 0.7; TGF‐1 β: 60.7 ± 12.4) and chemotactic index (1.3 ± 0.2) were observed. Moreover, there was an improvement of insulin secretion (3.8 ± 0.3, 4.7 ± 0.6 and 3.5 ± 0.2 respectively in response to glucose, arginine, and glibenclamide) and glucose oxidation, and a partial recovery of the measured mRNA expressions. Conclusions These novel results, obtained with islets prepared from patients with type 1 diabetes, demonstrate that even after months after diabetes diagnosis, a period of culture of the islets in a more favorable environment has beneficial effects on the islet function. Copyright © 2004 John Wiley & Sons, Ltd.