Insulin release failing

Q55 Avandia is useful when there is failing insulin release. Avandia reduces peripheral insulin resistance. 

Avandia contains rosiglitazone, which is a thiazolidinedione that is used as oral antidiabetic therapy. Thiazolidinediones reduce peripheral insulin resistance, resulting in reductions in blood-glucose concentrations. Inadequate response to oral antidiabetic therapy indicates failing insulin release and the impact of the introduction of rosiglitazone is of limited benefit on patient outcomes. Insulin should be considered. 

In terms of insulin release, catalytic systems offer the advantage of failing safe, i.e., for transport to increase, pH must be actively reduced by the enzyme-catalyzed reaction. Loss of enzyme activity leads to a reduction rather than an increase in release. Conversely, in binding displacement systems protein denaturation will lead to an increase in release as the number of cross-hnks is reduced. 

One-to-one random copolymers of acrylic acid with either hydroxyethyl acrylate (a hydrogel model) or methyl acrylate failed to protect insulin from release under gastric conditions (Figure 6). In the case of the hydrogel, the expected swelling due to exposure to water occurred, releasing insulin. The behavior of the ester copolymer led to the prediction that there should be no more than about four carbon atoms per carboxylic acid group in a repeat unit of the polymers. We have not been able to disprove this hypothesis thus far. 

If an insulin-dependent diabetic who has failed to take insulin, is suffering from an illness, or is subjected to stress, blood glucose may rise markedly. Elevated glucagon levels cause adipose tissue to release increased amounts of fatty acids, which are converted to ketone bodies by the liver. Ketone body levels may become extremely high, causing a metabolic acidosis that, if not treated rapidly and effectively, may lead to coma and death. 

Noninsulin-dependent diabetes mellitus (NIDDM Type II) is due to decreased release of insulin or decreased response of tissue to insulin (e.g., decreased number of insulin receptors) resulting in h)q)erglycemia but not ketoacidosis. Treatment focuses on diet and exercise, oral hypoglycemic drugs if diet fails, and insulin when all else fails. 

The pharmacokinetics and the pharmacodynamics of these co-crystals were evaluated in vivo with 2 nmol kg doses in somatostatin-treated beagle dogs, an animal model used for acute insulin deficiency. As a control, the time-action profile for the C8-HI molecule was compared to that of insulin. However, the former failed to demonstrate the protracted time action exhibited by the co-crystals, although their biopotencies in glucose reduction were similar. This underlines the necessity of the C8-HI, as part of the co-crystal lattice, for its controlled release action. 

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