Improved insulin secretory function and reduced chemotactic properties after tissue culture of islets from type 1 diabetic patients.
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-alpha: 112.9 +/- 5.6 vs 75.6 +/- 24.4; INF-gamma: 286.9 +/- 26.9 vs 58.6 +/- 6.2; IL-10: 41.8 +/- 4.3 vs 10.1 +/- 3.2; TGF-1 beta: 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-alpha: 55.7 +/- 2.3; INF-gamma: 53.9 +/- 4.3; IL-10: 8.6 +/- 0.7; TGF-1 beta: 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.
Lupi
Roberto
R
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa, Italy.
Marselli
Lorella
L
Dionisi
Sabrina
S
Del Guerra
Silvia
S
Boggi
Ugo
U
Del Chiaro
Marco
M
Lencioni
Cristina
C
Bugliani
Marco
M
Mosca
Franco
F
Di Mario
Umberto
U
Del Prato
Stefano
S
Dotta
Francesco
F
Marchetti
Piero
P
D000293:Adolescent; D000328:Adult; D002633:Chemotaxis; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics; D005941:Glucokinase / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D011770:Pyruvate Kinase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046509:Tissue Culture Techniques
D016207:Cytokines; D007328:Insulin; D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D005941:Glucokinase; D011770:Pyruvate Kinase; D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose