Insulin hypoglycemic effects

When certain drug s are administered with insulin, a resultant decrease or increase in hypoglycemic effect can occur. Display 49-1 identifies selected dragp that decrease the hypoglycemic effect of insulin. 

DISPLAY 49-1 Select Drugs That Decrease the Hypoglycemic Effect of Insulin... 

When oral antidiabetic drug are combined with other antidiabetic drug (eg, sulfonylureas) or insulin, the hypoglycemic effect may be enhanced. Elderly, debilitated, or malnourished patients are more likely to experience hypoglycemia... 

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin liposomes, Diabetes, 31. 506-511. 

Frati AC, Jimenez E and Ariza CR. 1990b. Hypoglycemic effect of Opuntia ficus-indica in non-insulin dependent diabetes mellitus patients. Phytother Res 4 195—197. 

Long-term administration of sulfonylureas to type 2 diabetics reduces serum glucagon levels, which may contribute to the hypoglycemic effect of the drugs. The mechanism for this suppressive effect of sulfonylureas on glucagon levels is unclear but appears to involve indirect inhibition due to enhanced release of both insulin and somatostatin, which inhibit alpha-cell secretion. 

Insulin [NE] Acute alcohol intake may increase hypoglycemic effect of insulin (especially in fasting patients). 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

Not only will the charge of a lipid and the composition of lipids affect the delivery of biomacromolecules, but the size of the liposome may alter the transport. Mixtures of insulin with three different diameter (1.98 pm, 0.4 pm, and 0.1 pm) neutral liposomes (DPPC Choi) resulted in similar overall hypoglycemic effects to insulin alone. Contrary to this finding is the fact that pulmonary absorption of liposomal [3H] terbutaline, a small molecule, has been reported to be dependent on both composition and size of the liposomes used (Abra et al. 1990). Differences in the absorption mechanism may be the explanation for this contradictory evidence further studies are needed to clarify this and other uncertainties about the uptake mechanism of macromolecules (Patton 1996). 

Prolonged hypoglycemic effect of insulin was reported after using poly(butyl cyanoacrylate) microparticles with a mean diameter of 254.7 nm (Zhang et al. 2001). Insulin-loaded poly(butyl cyanoacrylate) microparticles were prepared by emulsion polymerization in the presence of insulin. Insulin-loaded microparticles were administered intratracheally to normal rats. The duration of glucose levels below 80% of baseline was maintained for a longer period when insulin was administered in... 

Kawashima, Y., Yamamoto, H., Takeuchi, H., Fujioka, S., and Hino, T. (1999). Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. J. Controlled Release, 62, 279-287. 

Zhang, Q., Shen, Z.C., and Nagai, T. (2001). Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int. J. Pharmaceutics, 218, 75-80. 

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