Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide. / Yanay, Ofer; Moralejo, Daniel H.; Kernan, Kelly; Brzezinski, Margaret; Fuller, Jessica M.; Barton, Randall W.; Lernmark, Ake; Osborne, William R.

I: Journal of Gene Medicine, Vol. 12, Nr. 6, 2010, s. 538-544.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

Yanay, O., Moralejo, D. H., Kernan, K., Brzezinski, M., Fuller, J. M., Barton, R. W., ... Osborne, W. R. (2010). Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide. Journal of Gene Medicine, 12(6), 538-544. https://doi.org/10.1002/jgm.1466

CBE

MLA

Vancouver

Author

Yanay, Ofer ; Moralejo, Daniel H. ; Kernan, Kelly ; Brzezinski, Margaret ; Fuller, Jessica M. ; Barton, Randall W. ; Lernmark, Ake ; Osborne, William R. / Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide. I: Journal of Gene Medicine. 2010 ; Vol. 12, Nr. 6. s. 538-544.

RIS

TY - JOUR

T1 - Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide

AU - Yanay, Ofer

AU - Moralejo, Daniel H.

AU - Kernan, Kelly

AU - Brzezinski, Margaret

AU - Fuller, Jessica M.

AU - Barton, Randall W.

AU - Lernmark, Ake

AU - Osborne, William R.

PY - 2010

Y1 - 2010

N2 - Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. Results: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean ± SEM) in untreated rats occurred at 56.5 ± 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 ± 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting β cells. Conclusions: Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.

AB - Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. Results: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean ± SEM) in untreated rats occurred at 56.5 ± 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 ± 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting β cells. Conclusions: Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.

KW - BB rats

KW - Bioisolator

KW - Diabetes

KW - GLP-1

KW - β cells

UR - http://www.scopus.com/inward/record.url?scp=77954574031&partnerID=8YFLogxK

U2 - 10.1002/jgm.1466

DO - 10.1002/jgm.1466

M3 - Article

VL - 12

SP - 538

EP - 544

JO - Journal of Gene Medicine

T2 - Journal of Gene Medicine

JF - Journal of Gene Medicine

SN - 1521-2254

IS - 6

ER -