Tissue barriers and novel approaches to achieve hepatoselectivity of subcutaneously-injected insulin therapeutics.
Tissue Barriers
; 4(2): e1156804, 2016.
Article
em En
| MEDLINE
| ID: mdl-27358753
ABSTRACT
Current subcutaneously (s.c.)-injected insulin (INS) products result in a hyperinsulin exposure to peripheral tissues (skeletal muscle and adipose) while INS hardly accesses to liver after injection. This unphysiological distribution raises risks of hypoglycemia episode and causes weight gain after long term treatment. An ideal INS replacement therapy requires the distribution or action of exogenous INS to more closely mimic physiological INS in terms of its preferential hepatic action. However, there are 2 factors that limit the ability of s.c. injected INS to restore the liver peripheral gradient in INS deficient diabetes patients (1) the transport of INS in capillary endothelium and peripheral tissues from the injection site; and (2) peripheral INS receptor (IR) mediated INS degradation. In this review, the tissue barriers against efficient liver targeting of s.c. injected INS are discussed and current advances in developing hepatoselective insulin therapeutics are introduced.
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MEDLINE
Assunto principal:
Sistemas de Infusão de Insulina
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Insulinas
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Hipoglicemiantes
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Fígado
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article