Diabetes, treatment with glucose responsive

Proteins can also be delivered transdermally using a lipid-based biphasic delivery system in therapeutic quantity. Insulin treatment (10-50 mg/g formulation) was administered by a transdermal patch adhered to the abdomen of anesthetized Sprague-Dawley rats made diabetic by a single injection of strep-tozotocin (55 mg/kg). Blood was sampled from a tail vein every 2-4 h for 48 h. Response to transdermally applied insulin was both pH and concentration dependent. Blood glucose was decreased by 55% in the treated animals with mean response duration of 15 h. Serum insulin level was 162 pg/mL. 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

Both PKC-pII and PKC-6 isoforms have been shown to be activated in aortic and vascular smooth muscle cells (VSMC) from diabetic rats, as well as in response to hyperglycemia (Koya and King 1998 Craven and DeRubertis 1989 Inoguchi et al. 1992 Kunisaki et al. 1994 Lee et al. 1999). Treatment of VSMCs with 22 mM glucose for 3 days increased the levels of DAG as well as PKC-pII by 50 and 110%,... 

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