Journal
BIOMATERIALS
Volume 34, Issue 32, Pages 7994-8001Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.021
Keywords
Translational medicine; Postprandial hyperglycemia; Hyperinsulinemia; Glucose utilization; Glucoregulatory activity
Funding
- National Science Council, Taiwan, Republic of China [NSC 101-2120-M-007-015-CC1]
- Chang Gung Memorial Hospital [CMRP391513, CMRPG3A0512]
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Current insulin therapy via subcutaneous administration can lead to occasional hypoglycemia and peripheral hyperinsulinemia, due to its nonphysiological route. This study evaluates the feasibility of using bovine insulin and exendin-4 in a form of combination therapy, as orally delivered by nanoparticles composed of chitosan and poly(gamma-glutamic acid) (CS/gamma PGA NPs), to control blood glucose levels in rats with type 2 diabetes mellitus (T2DM) undergoing the oral glucose tolerance test. Experimental results indicate that CS/gamma PGA NPs could enhance the intestinal paracellular permeation; consequently, the exogenous bovine insulin and exendin-4 could be delivered into the liver and pancreas, where they could elicit their glucoregulatory activities. In response to the stimulus of exogenously delivered bovine insulin and the endogenously secreted rat insulin stimulated by the ingested exendin-4, significant glucose utilizations were found in the cardiac and skeletal muscles, resulting in the glucose-lowering effect. Owing to its synergic stimulation effects, the hypoglycemic effect of oral ingestion of NPs containing bovine insulin and exendin-4 was significantly greater than that of the group solely treated with insulin NPs. Above results demonstrate that oral combination therapy with bovine insulin and exendin-4 improves the modulation of blood glucose levels in T2DM rats, making it highly promising for treating those T2DM patients not adequately controlled by the current insulin therapy. (C) 2013 Elsevier Ltd. All rights reserved.
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