Glucose-insulin conjugate

The enhancement of nasal absorption of insulin by hydrophobic bile salts has also been investigated. It was found that minor differences in the number, position, and orientation of the nuclear hydroxyl groups as well as alterations to side-chain conjugation can improve the adjuvant potency of bile salts. Moreover, the absorption of insulin positively correlated with an increase in the hydrophilicity of the steroid nucleus of the bile salts. In the presence of bile salts, nasal absorption of insulin reached peak levels within about lOmin, and some 10-20% of the dose was found to have been absorbed into the circulation. Marked increases in serum insulin levels were seen with sodium deoxycholate, the most lipophilic of the bile salts, whereas the least elevation—as well as least lowering of blood glucose levels—was seen with the most hydrophobic bile salt, sodium ursodeoxycholate [63],... 

Another method of delivery of insulin is to conjugate the protein with transferrin. Oral administration of the insulin-transferrin complex and insulin in streptozotocin-induced diabetic mice lowered the blood glucose levels by 28 and 5%, respectively. The blood glucose level was further decreased to 40% when the mice were pretreated with brefeldin A, a fungal metabolite, before the administration of the insulin-transferrin complex. The potentiation by brefeldin A indicated that insulin absorption could be accomplished through a transferrin receptor-mediated transcytosis in the intestinal wall. 

Liu, F., et al. Glucose-induced release of glycosylpoly(ethylene glycol) insulin bound to a soluble conjugate of concanavalin A. Bioconjugate Chemistry, 1997, 8(5), 664-672. 

Ryder, J.W., Portocarrero, C.P., Song, XM., Cui, L., Yu, M., Combatsiaris, T., Galuska, D., Bauman, D ., Barbano, DM., Charron, M J., Zierath, JR., and Houseknecht, Kl. (2001) Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid. Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression, Diabetes 50,1149-1157. 

Proteins are polypeptides containing from 50 to thousands of amino acid residues, and they vary greatly in structure and composition. They can he divided into two classes simple and conjugated. Simple proteins consist only of amino acids. Two examples of simple proteins are insulin and chymotrypsin. Insulin, a hormone that is essential to controlling the concentration of glucose in the blood, has 51 amino acid residues in two linked chains (Figure 15.10). Chymotrypsin, an enzyme that aids in the digestion of proteins in our diet, contains 245 amino acid residues. 

Bauman, D.M. Barbano, M.J. Charron, et al. Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid. Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression. Diabetes 50 1149-1157 (2001). 

Henriksen, E.J., Teachey, M.K., Taylor, Z.C., Jacob, S., Saengsirisuwan, V., Kramer, K., Klatt, M.J., Ptock, A., and Hasselwander, O. (2002) Metabolic Effects of Conjugated Linoleic Acid on Insulin Resistant Rat Skeletal Muscle Glucose Transport Are Isomer Specific, Diabetes 51, A309 (Abstr.). 

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