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Encapsulated, Genetically Engineered Cells, Secreting Glucagon‐like Peptide‐1 for the Treatment of Non‐insulin‐dependent Diabetes Mellitus
Author(s) -
BURCELIN RÉMY,
ROLLAND ERIC,
DOLCI WANDA,
GERMAIN STÉPHANE,
CARREL VÉRONIQUE,
THORENS BERNARD
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08510.x
Subject(s) - hypoglycemia , medicine , insulin , endocrinology , diabetes mellitus , type 2 diabetes mellitus , glucagon , hormone , glucagon like peptide 1 , secretion , in vivo , type 2 diabetes , biology , microbiology and biotechnology
Non‐insulin‐dependent, or type II, diabetes mellitus is characterized by a progressive impairment of glucose‐induced insulin secretion by pancreatic β cells and by a relative decreased sensitivity of target tissues to the action of this hormone. About one third of type II diabetic patients are treated with oral hypoglycemic agents to stimulate insulin secretion. These drugs however risk inducing hypoglycemia and, over time, lose their efficacy. An alternative treatment is the use of glucagon‐like peptide‐1 (GLP‐1), a gut peptidic hormone with a strong insulinotropic activity. Its activity depends of the presence of normal blood glucose concentrations and therefore does not risk inducing hypoglycemia. GLP‐1 can correct hyperglycemia in diabetic patients, even in those no longer responding to hypoglycemic agents. Because it is a peptide, GLP‐1 must be administered by injection; this may prevent its wide therapeutic use. Here we propose to use cell lines genetically engineered to secrete a mutant form of GLP‐1 which has a longer half‐life in vivo but which is as potent as the wild‐type peptide. The genetically engineered cells are then encapsulated in semi‐permeable hollow fibers for implantation in diabetic hosts for constant, long‐term, in situ delivery of the peptide. This approach may be a novel therapy for type II diabetes.